agenticx/DrugbankRawParquet · Datasets at Hugging Face

DB00001

Lepirudin

Lepirudin is a recombinant hirudin formed by 65 amino acids that acts as a highly specific and direct thrombin inhibitor.[L41539,L41569] Natural hirudin is an endogenous anticoagulant found in _Hirudo medicinalis_ leeches.[L41539] Lepirudin is produced in yeast cells and is identical to natural hirudin except for the absence of sulfate on the tyrosine residue at position 63 and the substitution of leucine for isoleucine at position 1 (N-terminal end).[A246609] Lepirudin is used as an anticoagulant in patients with heparin-induced thrombocytopenia (HIT), an immune reaction associated with a high risk of thromboembolic complications.[A3, L41539] HIT is caused by the expression of immunoglobulin G (IgG) antibodies that bind to the complex formed by heparin and platelet factor 4. This activates endothelial cells and platelets and enhances the formation of thrombi.[A246609] Bayer ceased the production of lepirudin (Refludan) effective May 31, 2012.[L41574]

solid

Lepirudin is indicated for anticoagulation in adult patients with acute coronary syndromes (ACS) such as unstable angina and acute myocardial infarction without ST elevation. In patients with ACS, lepirudin is intended for use with [aspirin].[L41539] Lepirudin is also indicated for anticoagulation in patients with heparin-induced thrombocytopenia (HIT) and associated thromboembolic disease in order to prevent further thromboembolic complications.[L41539]

Lepirudin is a recombinant hirudin that acts as a highly specific thrombin inhibitor. Its activity is measured by anti-thrombin units (ATUs) that correspond to the amount of lepirudin required to neutralize a unit of the World Health Organization α-thrombin (89/588) standard. The activity of lepirudin is 16,000 ATU/mg.[L41539,L41569] A single molecule of lepirudin binds to a molecule of thrombin, blocking its thrombogenic activity. This drug increases activated partial thromboplastin time (aPTT) and PT (INR) values in a dose-dependent manner, and its mode of action is independent of antithrombin III.[L41539,L41569] Platelet factor 4 does not inhibit lepirudin.[L41539,L41569] The pharmacodynamic effect of lepirudin was evaluated by measuring an increase in aPTT. No saturable effect was observed at the highest tested dose (0.5 mg/kg, IV bolus).[L41539] Thrombin time was considered an unsuitable routine test for lepirudin monitoring due to the high values detected (200 seconds) even at low doses.[L41539] The concomitant use of thrombolytic therapy and lepirudin is not recommended due to the high risk of bleeding that may be life-threatening. In patients with a risk of bleeding, a physician should weigh the risks of lepirudin administration against its benefits. There is also an especially high risk of bleeding in patients who weigh less than 50 kg, and a lower dosage is required. Patients with renal impairment have a higher risk of hemorrhagic adverse events.[L41539]

Lepirudin is a direct thrombin inhibitor used as an anticoagulant in patients for whom heparin is contraindicated.[L41539,A3] Thrombin is a serine protease that participates in the blood-clotting cascade, and it is formed by the cleavage of pro-thrombin. Active thrombin cleaves fibrinogen and generates fibrin monomers that polymerize to form fibrin clots.[A246624] Lepirudin binds to the catalytic and substrate-binding sites of thrombin, forming a stable, irreversible and non-covalent complex.[A246609] This blocks the protease activity of thrombin and inhibits the coagulation process. Each molecule of lepirudin binds to a single molecule of thrombin,[L41539] and unlike [heparin], it is able to inhibit thrombin in both its clot-bound or free states.[A246609]

Lepirudin administered as a single intravenous bolus injection of 0.4 mg/kg in 9 healthy volunteers (male and female) resulted in a Cmax of 2924 ng/mL, a tmax of 0.17 h and an AUC0-∞ of 2500 ng•h/mL.[L41539] When 0.1, 0.15 and 0.2 mg/kg of lepirudin was administered as a single intravenous infusion over 6 hours in healthy male volunteers, lepirudin had a corresponding Cmax of 111, 203, and 2446 ng/mL and a corresponding AUC of 612, 1184, and 1446 ng•h/mL.[L41544] Bioavailability is 100% following injection. Also, it has been reported that following subcutaneous (sc) administration, the bioavailability of lepirudin is almost 100%.[A246609]

As a polypeptide, lepirudin is expected to be metabolized by the sequential cleavage of amino acids by kidney exoproteases, which have carboxypeptidase and dipeptidase-like activity.[L41539,L41544] The C-terminal cleavage of lepirudin aminoacids (aminoacids 1 to 65) produces four metabolites with anti-thrombotic activity: M1 (aminoacids 1 to 64), M2 (aminoacids 1 to 63), M3 (aminoacids 1 to 62), and M4 (aminoacids 1 to 61).[L41544]

The acute toxicity of intravenous lepirudin was evaluated in mice (0.1-1000 mg/kg), rats (1-1000 mg/kg), and monkeys (1-100 mg/kg), and toxicity was not detected at the doses investigated.[L41539] The acute toxicity of lepirudin administered subcutaneously was also evaluated in mice (1-1250 mg/kg) and rats (1-500 mg/kg), and no toxicity was detected.[L41539] One rat (100 mg/kg) died of rapid blood loss after the subcutaneous administration of lepirudin. Reactions to local injections such as hemorrhages, hematomas and/or nodules were detected in mice and rats given subcutaneous doses of lepirudin equal or higher than 500 mg/kg and 10 mg/kg, respectively.[L41539] Chronic toxicity was evaluated in rats and monkeys given lepirudin for up to 3 months. Most of the effects observed were due to the antithrombotic action of lepirudin. After 3 months, hemosiderin deposits in the spleen and moderate sinus histiocytosis in the lymph node were observed in rats. In monkeys, external and internal hemorrhages and hematomas were detected.[L41539] Lepidurin was reported as not mutagenic.[L41539] Relative overdose may occur in patients with renal impairment, therefore, bolus dose and rate of infusion must be reduced in case of known or suspected renal insufficiency.[L41539] Excessively high activated partial thromboplastin time (aPTT) values suggest an overdose and a risk of bleeding. Lepirudin has no known antidote. In case of life-threatening bleeding and if excessive plasma levels of lepirudin are suspected: 1)stop the administration of lepirudin immediately, 2) determine aPTT and coagulation parameters, 3) determine hemoglobin, and prepare for a transfusion, 4) follow the treatment guidelines for patients with shock.[L41539] Hemofiltration or hemodialysis may be useful in case of overdose, based in single case reports and animal data.[L41539]

Lepirudin has an initial half-life of approximately 10 minutes, and in young healthy volunteers, it has a terminal half-time of 1.3 hours.[L41539] Lepirudin has a first-order elimination kinetic; plasma concentration increases proportionally as the lepirudin intravenous dose is increased. Elimination half-life values of up to 2 days were detected in patients with marked renal insufficiency (creatinine clearance < 15 mL/min).[L41539]

In human plasma, the protein binding of lepirudin was approximately 3%.[L41539]

Lepirudin is mostly excreted through urine (48.3%). About 35% of lepirudin is excreted unchanged, while metabolites are found in a smaller proportion (2.5% of M1, 5.4% of M2, 3.9% of M3 and 1.6% of M4).[L41544]

The volume of distribution of lepirudin at steady state was 12.2 L in healthy young subjects (n=18, 18-60 years), 18.7 L in healthy elderly subjects (n=10, 65-80 years), 18.0 L in renally impaired subjects (n=16, creatinine clearance < 80 mL/min, and 32.1 L in heparin-induced thrombocytopenia patients (n=73).[L41539] The distribution of lepirudin is mainly restricted to extracellular fluids.[L41539]

The clearance of lepirudin is proportional to the glomerular filtration rate. On average, lepirudin clearance was 164 mL/min in healthy young subjects (n=18, 18-60 years) and 25% lower in women than in men. In healthy elderly subjects (n=10, 65-80 years), clearance was 139 mL/min, about 20% lower than in younger patients.[L41539] This is possibly due to the lower creatinine clearance in elderly patients. In renally impaired subjects (n=16, creatinine clearance < 80 mL/min), clearance was 61 mL/min, and in heparin-induced thrombocytopenia patients (n=73), it was 114 mL/min.[L41539]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "withdrawn" ]

[ "B01AE", "B01A", "B01", "B" ]

[ "Humans and other mammals" ]

[ { "cost": "273.19", "description": "Refludan 50 mg vial", "unit": "vial" } ]

[ { "approved": "1993-01-19", "country": "United States", "expires": "2010-01-19", "number": "5180668" } ]

[ "Refludan", "Refludan", "Refludan", "Refludan", "Refludan", "Refludan" ]

[]

[ "P00734" ]

[]

DB01022

Phylloquinone

Vitamin K1, also called phylloquinone or phytonadione, is a fat soluble vitamin.[L33319,L33345] Phylloquinone is a cofactor of the enzyme γ-carboxylase, which modifies and activates precursors to coagulation factors II, VII, IX, and X.[A234264,A234195,A234259] It is indicated in the treatment of coagulation disorders due to faulty formation of coagulation factors II, VII, IX, and X caused by deficiency or interference in the activity of vitamin K.[L33319] Phylloquinone has been synthesized since at least 1939,[A234384] and was approved by the FDA prior to 1955.[L33389]

liquid

Oral phylloquinone is indicated to treat prothrombin deficiency caused by coumarin or indanedione derivatives; and hypoprothrombinemia secondary to antibacterial therapy, salicylates, or obstructive jaundice or biliary fistulas with concomitant bile salt administration.[L33345] Parenteral (intravenous, intramuscular, and subcutaneous) phylloquinone is indicated to treat coagulation disorders due to faulty formation of coagulation factors II, VII, IX, and X caused by vitamin K deficiency or some interference with vitamin K activity.[L33319] These indications include the above indications as well as hypoprothrombinemia secondary to sprue, ulcerative colitis, celiac disease, intestinal resection, pancreatic cystic fibrosis, or regional enteritis; or hypoprothrombinemia caused by interference with vitamin k metabolism.[L33319]

Phylloquinone is a vitamin K indicated in the treatment of coagulation disorders due to faulty formation of coagulation factors II, VII, IX, and X caused by deficiency or interference in the activity of vitamin K.[L33319] It has a long duration of action as vitamin K is cycled in the body,[A234259] and a wide therapeutic index as large doses can be tolerated.[A234284,L33345] Patients should have their prothrombin time monitored during therapy and healthcare professionals should be aware of the increased risk of hypersensitivity reactions with parenteral administration.[L33345]

Vitamin K is a cofactor of gamma-carboxylase.[A234264,A234195] Gamma carboxylase attaches carboxylic acid functional groups to glutamate, allowing precursors of factors II, VII, IX, and X to bind calcium ions.[A234259] Binding of calcium ions converts these clotting factors to their active form, which are then secreted from hepatocytes into the blood, restoring normal clotting function.[L33345] Vitamin K may also carboxylate matrix proteins in chondrocytes, inhibiting calcification of joints, and may increase type II collagen.[A234304] The role of vitamin K in osteroarthritis,[A234304] bone density,[A234309] and vascular calcification[A234314] is currently under investigation.

A 4 µg oral dose of phylloquinone is 13% ± 9% bioavailable, with a Tmax of 4.7 ± 0.8 hours.[A234264] 1.5 ± 0.8 nmol is found in the plasma compartment, and 3.6 ± 3.4 nmol is found in the second compartment.[A234264] A 10 mg intramuscular phylloquinone dose is 89.2% ± 25.4% bioavailable.[A234344] The same dose reaches a mean Cmax of 67 ± 30 ng/mL, with a mean Tmax of 9.2 ± 6.6 hours, and an AUC of 1700 ± 500 h\*ng/mL.[A234344] A 10 mg intravenous phylloquinone dose has a mean AUC of 1950 ± 450 h\*ng/mL.[A234344]

Phylloquinone's phytyl side chain is omega hydroxylated by CYP4F2.[A137578] The side chain is then cleaved to 5 or 7 carbons long, and then glucuronidated prior to elimination.[A234104,A234109,A234114,A234119] Vitamin Ks in general undergo a cycle of reduction to vitamin K hydroquinone by vitamin K epoxide reductase (VKOR), oxidation to vitamin K epoxide by gamma-glutamyl carboxylase, and converted back to vitamin K by VKOR.[A234259]

High doses of vitamin K1 are not associated with toxicity.[A234259] Intravenous administration has been associated with an increased risk of toxicity.[A234284] These patients should be treated with symptomatic and supportive measures. The intravenous LD50 in mice is 1170 mg/kg and the oral LD50 is >24180 mg/kg.[L33345]

Intravenous phylloquinone has an initial half life of 22 minutes, followed by a half life of 125 minutes.[A234104]

null

Intravenous phylloquinone is 36% eliminated in the feces in 5 days and 22% recovered in urine in 3 days.[A234104,A234329]

The steady state volume of distribution of phylloquinone is 20 ± 6 L in subjects who are also taking phenprocoumon therapy.[A234374]

Intravenous phylloquinone is 90% cleared in 2 hours, and 99% cleared in 8 hours.[A234104,A234329] A 10 mg intravenous dose of phylloquinone has a mean clearance of 91 ± 24 mL/min.[A234344]

Organic compounds

Lipids and lipid-like molecules

Prenol lipids

Quinone and hydroquinone lipids

[ "approved", "investigational" ]

[ "B02BA", "B02B", "B02", "B" ]

[ "Humans and other mammals" ]

[ { "cost": "2.76", "description": "Vitamin K1 10 mg/ml", "unit": "ml" }, { "cost": "4.79", "description": "Vitamin K1 Pediatric 2 mg/ml", "unit": "ml" }, { "cost": "5.95", "description": "Mephyton 5 mg tablet", "unit": "tablet" }, { "cost": "35.0", "description": "Vitamin k1 liquid", "unit": "g" }, { "cost": "66.0", "description": "Phytonadione liquid", "unit": "g" }, { "cost": "111.13", "description": "Phytonadione crystal", "unit": "g" } ]

[]

[ "Adeks - Dps", "Adeks Tablets", "Adult Infuvite Multiple Vitamins", "Adult Infuvite Multiple Vitamins", "Adult Infuvite Multiple Vitamins", "Adult Infuvite Multiple Vitamins", "AquaMEPHYTON", "AquaMEPHYTON", "Decara K Vegicaps", "Infuvite Adult", "Infuvite Adult", "Infuvite Pediatric", "Infuvite Pediatric", "M.V.I. Adult", "M.V.I. Adult", "M.V.I. Paediatric", "M.V.I. Pediatric", "Mephyton", "Mephyton", "Mephyton", "Mephyton", "Mephyton", "Mephyton", "Mephyton", "Mephyton", "Mephyton", "Mephyton", "Mephyton", "Multi-12/k1 Pediatric", "Mvc 9+4 Inj", "Omega-3 Rx Complete", "Pediatric Infuvite Multiple Vitamins", "Pediatric Infuvite Multiple Vitamins", "Pediatric Infuvite Multiple Vitamins", "Pediatric Infuvite Multiple Vitamins", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione", "Phytonadione Inj 2mg/ml", "Phytonadione Phytonadione", "Pro Hers Vanilla", "Pro Pcos Citrus", "Truemed Group LLC", "Vitalipid N", "Vitalipid N", "Vitalipid N", "Vitamin D2 and K1", "Vitamin K1", "Vitamin K1", "Vitamin K1", "Vitamin K1", "Vitamin K1", "Vitamin K1", "Vitamin K1", "Vitamin K1", "Vitamin K1", "Vitamin K1 - Phytonadione", "Vitamin K1 Inj 10mg/ml", "Vitamin K1 Inj 2mg/ml", "Vitamin K1 Phytonadione" ]

[ "Aqua-Mephyton", "Konakion" ]

[ "Omega-3 Rx Complete", "M.V.I. Pediatric", "Pro Pcos Citrus", "Pro Hers Vanilla", "M.V.I. Adult", "M.V.I. Adult", "Pediatric Infuvite Multiple Vitamins", "Pediatric Infuvite Multiple Vitamins", "Adult Infuvite Multiple Vitamins", "Adult Infuvite Multiple Vitamins", "Pediatric Infuvite Multiple Vitamins", "Pediatric Infuvite Multiple Vitamins", "Adult Infuvite Multiple Vitamins", "Adult Infuvite Multiple Vitamins", "Decara K Vegicaps", "Mvc 9+4 Inj", "M.V.I. Paediatric", "Multi-12/k1 Pediatric", "Adeks - Dps", "Adeks Tablets", "Vitamin D2 and K1", "Vitalipid N", "Vitalipid N", "Vitalipid N", "Infuvite Adult", "Infuvite Adult", "Infuvite Pediatric", "Infuvite Pediatric" ]

[ "P38435", "P02818" ]

[ "P78329", "Q9Y5Z9", "Q9BQB6" ]

[]

DB01373

Calcium

Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. The skeleton acts as a major mineral storage site for the element and releases Ca2+ ions into the bloodstream under controlled conditions. Circulating calcium is either in the free, ionized form or bound to blood proteins such as serum albumin. Although calcium flow to and from the bone is neutral, about 5 mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Low calcium intake may also be a risk factor in the development of osteoporosis. The best-absorbed form of calcium from a pill is a calcium salt like carbonate or phosphate. Calcium gluconate and calcium lactate are absorbed well by pregnant women. Seniors absorb calcium lactate, gluconate and citrate better unless they take their calcium supplement with a full breakfast.

solid

Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. It is vital in cell signaling, muscular contractions, bone health, and signalling cascades.

Calcium (Ca2+) plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization. Many enzymes require calcium ions as a cofactor, those of the blood-clotting cascade being notable examples. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation.

Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. More than 500 human proteins are known to bind or transport calcium. The skeleton acts as a major mineral storage site for the element and releases Ca2+ ions into the bloodstream under controlled conditions. Circulating calcium is either in the free, ionized form or bound to blood proteins such as serum albumin. Parathyroid hormone (secreted from the parathyroid gland) regulates the resorption of Ca2+ from bone. Calcitonin stimulates incorporation of calcium in bone, although this process is largely independent of calcitonin. Although calcium flow to and from the bone is neutral, about 5 mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Low calcium intake may also be a risk factor in the development of osteoporosis. The best-absorbed form of calcium from a pill is a calcium salt like carbonate or phosphate. Calcium gluconate and calcium lactate are absorbed well by pregnant women. Seniors absorb calcium lactate, gluconate and citrate better unless they take their calcium supplement with a full breakfast. The currently recommended calcium intake is 1,500 milligrams per day for women not taking estrogen and 800 milligrams per day for women on estrogen. There is close to 300 milligrams of calcium in one cup of fluid milk. Calcium carbonate is currently the best and least expensive form of calcium supplement available.

null

The kidney excretes 250 mmol a day in urine, and resorbs 245 mmol, leading to a net loss in the urine of 5 mmol/d.

null

[ "nutraceutical" ]

[ "M05BB", "M05B", "M05", "M", "A11AA", "A11A", "A11", "A", "M05BB", "M05B", "M05", "M", "A11GB", "A11G", "A11", "A", "M05BB", "M05B", "M05", "M", "M05BB", "M05B", "M05", "M", "M05BB", "M05B", "M05", "M" ]

[ "Humans and other mammals" ]

[]

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C & D", "Calcium With Vitamin D 200 Mg/160 Iu", "Calcium/magnesium Drink", "Calcor", "Calplus", "Card-floe II Tab", "Cavan One", "Cavan-EC SOD DHA", "Cell-wise", "Cell-wise Natural Source", "Central-vite 18 Essential", "Century Complete", "Chela Calmag-100 Plus Zinc D3", "Chela Calmag-300 Plus Zinc D3", "Chelamins Plus Tab", "Chelated Cal-mag(2:1)with Zn Vit.c and D", "Chelated Cal/mag/zn With Vitamins", "Chelated Calcium and Magnesium Tab", "Chelated Calcium Supplement - 150mg Tab", "Chelazome Calcium 125mg", "Chewable Adult Multivitamins With Minerals", "Chewable Cal-mag Chocolate Flavour", "Chewable Calcium & Magnesium 2:1 Tablet", "Chewable Calcium Plus Magnesium and Minerals", "Chewable Children's Complete Multivitamins With Essential Minerals", "Children's Chewable Multi-vitamin Complete With Minerals", "Children's Chewable Multivitamin Complete With Minerals", "Children's Chewable Multivitamins and Minerals", "Children's Chewable Multivitamins With Minerals", "Classic Swiss One 10 Multivitamin and Mineral Tab", "Complete Multivitamins and Minerals Tablets Timed Release", "Complete One A Day Tab", "Complete One-A-day - Tab", "D T B T", "Doctor's Choice Brand for Men", "ENA Actimineral A", "Envirocomplex", "Enviroflex - Tab", "Essential Vitamins and Minerals", "Extra Once A Day", "Fem Time Tab", "Ferrous Sulfate", "Focalgin B", "Folcaps Omega-3", "Folgard", "For-2", "Formula A.R.-th Dietary Supplement", "Formula Inf", "Formula Int", "Formula O-care Vitamin and Mineral Supplement", "Formula Osg", "Fusion Activator Formula Tab", "Fusion PM Formula Tab", "Gellucal Cap 45mg", "Global Vigen Recare Calcium", "Grand Master Formula Tab", "Great Calcium", "Great Calcium", "H.W. Children's Chewable Multi Vit & Mineral", "HANTAI 8030 Ca-D3 GOLD", "HANTAI 8030 Ca-D3 GOLD", "HANTAI 8030 Ca-D3 Premium", "HANTAI 8030 Ca-D3 Premium", "HANTAI 8030 Ca-D3 Premium", "Hemarexin Tab", "Hi Potency Multi Tab", "Hsn Formula", "Hvp Chelated Cal/mag With Zinc and Vitamins C and D", "Hypo Vites Tab", "Innersource Tab", "Isotonix Calcium Plus Formula", "K.L. Vitamin-mineral", "Kanga-V Multivitamins & Minerals", "Korea Calcium King", "Korea Calcium King", "Korea Calcium King", "L.G.I.T.", "Leonas Calcium Plus Vitamin D3", "Liquid Calcium and Magnesium With Vit.d", "Liquid Calcium Mg Phosphorus and Vit.d-3", "Liquid Calcium With Vitamin D", "Liquid Opti-minplex +d", "Luna Vitamin and Mineral Bar for Women", "M-Natal Plus", "M-Natal Plus", "M-Natal Plus", "M-Natal Plus", "Mag/cal 1:1 Capsules W Vitamin D", "Magnacal", "Magnesium Chloride", "Maintain Multiple Vitamin & Minerals", "Maximum Once A Day", "Maxine Vitamin and Mineral Supplement", "Maxum Multi-vite", "Mega Capsules", "Mega Multiple Minerals", "Mega Plex III - Pck", "Mega Plex III - Pck", "Mega Plex IV - Pck", "Mega Plex IV - Pck", "Mega-vim 75 With Beta-carotene - Tablets", "Mega-vim 75 With Beta-carotene - Tablets", "Men's", "Men's 50+", "Men's Biomultiple Vitamin and Mineral Supplement", "Milltrium Senior Vitamin and Mineral Supplement", "Mineral Support", "Mnps Formula Supplement", "Mor-vites Tab", "Multi #2", "Multi Cal Mag Liquid", "Multi Flow Tablets", "Multi II IV Vi Tab", "Multi Mega Minerals With Vitamin D", "Multi Plex I - Tab", "Multi Plex II - Tab", "Multi Rol", "Multi Spectrum - Tablet", "Multi Tabs", "Multi Vitamin & Minerals", "Multi Vitamins & Minerals", "Multi-actin", "Multi-mins Minerals", "Multi-vitamins With Minerals", "Multicaps", "Multimineral Chelates", "Multimineral Tablets", "Multiminerals", "Multipack II", "Multiple Mineral Liquid", "Multiple Minerals", "Multiple Vitamin Plus Minerals Tab", "Multiple Vitamins and Minerals Tab", "Multiple Vitamins W Minerals Tab", "Multiple Vitamins With Minerals Tablets", "Multitabs", "Multivitamin & Minerals (iron Free)", "Multivitamin & Multimineral", "Multivitamines Et Mineraux Reguliers / Regular Multivitamins and Minerals", "Multivitamins and Minerals - Complete", "Multivitamins and Minerals for Men", "Multivitamins and Minerals for Women", "Multivitamins and Minerals Tablets", "Multivitamins and Minerals With Betacarotene Tablets", "Multivitamins and Multiminerals Formula Regular Tablet", "Multra Plex", "Multra With Iron", "Nata Komplete", "Natelle One", "Natural Liquid Mineral Supplement", "Natural Source Spectrum With Beta Carotene", "Neonatal Plus Vitamin", "Neonatal Vitamin", "NESTABS ABC Prenatal Multi-vitamin/Mineral Supplement with DHA/EPA", "Nexa Plus", "Nexa Plus", "Nexa Select Rx Prenatal Vitamin with Plant-Based DHA", "Nitro Vites - Tab", "Nutra Boost", "Nutra-clear", "Nutri-chem Cal Mag", "Nutri-chem Calcium Magnesium With D and Zinc", "Nutrifer Plus Tablets", "Nutrilite Double X", "Nutrilite Double X", "Nutrilite Double X", "O-Cal FA multivitamin", "O-Cal Prenatal Vitamin", "Olympian Multi Vit Plus Minerals Tab", "Omega-3 Rx Complete", "One A Day Advance Adults", "One A Day Advance Adults 50+", "One A Day Multiple Vit W Minerals", "One A Day Tab", "One Daily Vitamin and Mineral Dietary Supplement", "Only One - Tablet", "OnlyCal", "Opti-cal Chewable +d Caplet", "Osteo Factors", "Osteo Formula", "Osteo Formula", "Osteo Formula", "Osteo Formula", "Osteo Formula Tab", "Osteo Regime", "Osteo Tablets", "Osteo-force", "Osteo-life", "Osteoligo", "Osteoshield", "Oyster Shell Calcium with Vitamin D", "Oyster Shell Calcium with Vitamin D", "P D All", "P D All M", "P D M", "Paramettes Adults", "Phytofortis + Calcium A-D", "Pnv-dha", "Pnv-dha", "Port A Mins Super Cal-mag 300/150 With Vitamin D3", "Port A Mins Super Cal-mag 600/300", "Port A Mins Super Calcium 375 With Vitamin D3", "Port A Mins Super Calcium 750 With Vitamin D3", "PreFol-DHA", "Premel", "Premium Prenatal", "Premium Prenatal - Tablets", "Prenara", "Prenatal", "Prenatal Formula Tab", "Prenatal Vi-min", "Prenatal Vitamin and Mineral Supplement", "Prenatal Vitamin No 53 Iron Fum Folic Acid Docusate CA DHA", "PreNatal Vitamins Plus", "PreNatal Vitamins Plus", "Prenatvite", "Prenatvite Complete", "Prenatvite Plus", "Preplus", "Preplus", "Prevencal 300 + D A Croquer", "Protect Plus SO 60", "Pure Calcium calcium", "Resto L", "Restoration Treatment", "Revitex Ampoules Et Comprimes", "Revival 1 Tab", "Right Choice P.M. Multi Formula - Caplet", "Rocky Mountain Multiple Vit and Min Mega Tab", "Senior Multi One", "Spd Tab", "Spectrum 2 Cap", "Spectrum Performa Multivitamins and Minerals Tablets", "Sub small molecule disinfectant", "Super Cal Mag Plus", "Super Kids Chewable Multivitamin Multimineral (chewable Tablets)", "Super Multi", "Super Vita Vim Multivitamins and Minerals", "Super Vita-vim With Beta-carotene - Tab", "Supplements De Vitamines Et Mineraux", "Swical D-M - Tab", "Swical Extra-fort", "Swical-energy 3e Age", "Swical-multi", "Swiss One", "Swiss One Multi Vit & Chel Min Tab", "Swiss One Multivitamin and Mineral Caplet", "Swiss Total One", "T-PA Cap", "Tall G U", "Tianshi Calcium With Natural Source Vitamin D Tablets", "Tianshi Vital Powder I", "Tianshi Vital Powder II", "Tianshi Vital Powder III", "Timed Release and Esterified Vitamin C-500", "Timed Release Vita-vim Srt", "Total Living Concepts Formula One - Tab", "Total Living Concepts Formula One - Tab", "Tri-mins - Cap", "Tropicana Calcium & Vitamin C Supplement", "Tropicana Calcium and Vitamin C Supplement", "Tropicana Calcium Supplement 344 mg", "Tropicana Calcium Supplement 393 mg", "Tropicana Calcium Supplement 604 mg", "Twin G.F. Powder", "Twin G.F. Powder", "Twin G.F. Powder Vanilla Flavor", "Twin Opti Pwr", "Ultimate Tab", "UltimateCare ONE NF", "Usana Calmag Plus Tablets - Tab", "Usana Multimineral Tablets", "Usana Multimineral Tablets - Tab", "Usana Optimizer Actical Plus Calcium-magnesium-vitamin D3-silicon Tablets", "V & M Vitamin and Mineral Supplement", "Vc II", "Vege 1 Daily Tab", "Vege Swiss One Multivitamin W Chel Mins Tab", "VIL-Rx", "Vimeral Tab", "Vimeral Tab", "Vita Balance 2000", "Vita Plex Tab", "Vita Vim Multivitamins and Minerals Tab", "Vita-vim - Tab", "Vitaflex Dietary Suplement", "Vitafol Caplet", "Vitafol OB Caplet", "Vitafol-OB Plus DHA Prenatal Supplement Plus DHA", "Vitalife - Capsule", "Vitality Brand Calcium Plus Tab", "Vitamin & Mineral Formula 1 Dietary Supplement", "Vitamin C W Chelates Tab", "Vitaplex", "Vyo Cylate - Pwr", "Women's Biomultiple Vitamin and Mineral Supplement", "Women's Change Formula", "Zingiber" ]

[]

[ "Pure Calcium calcium", "Oyster Shell Calcium with Vitamin D", "O-Cal Prenatal Vitamin", "Cavan One", "Zingiber", "PreNatal Vitamins Plus", "Prenatal Vitamin No 53 Iron Fum Folic Acid Docusate CA DHA", "Vitafol Caplet", "Ferrous Sulfate", "PreFol-DHA", "Focalgin B", "Nata Komplete", "PreNatal Vitamins Plus", "Cavan-EC SOD DHA", "Nexa Plus", "Nexa Select Rx Prenatal Vitamin with Plant-Based DHA", "UltimateCare ONE NF", "Folcaps Omega-3", "B-Nexa", "B-Nexa", "Pnv-dha", "Pnv-dha", "Neonatal Plus Vitamin", "Omega-3 Rx Complete", "Natural Liquid Mineral Supplement", "Preplus", "Prenatal", "Magnesium Chloride", "Neonatal Vitamin", "Leonas Calcium Plus Vitamin D3", "Preplus", "Vitafol OB Caplet", "Oyster Shell Calcium with Vitamin D", "Prenatvite", "Prenatvite Plus", "Prenatvite Complete", "M-Natal Plus", "Prenara", "Sub small molecule disinfectant", "Revival 1 Tab", "Nutrifer Plus Tablets", "Prenatal Vitamin and Mineral Supplement", "Vita Plex Tab", "Premium Prenatal - Tablets", "Vyo Cylate - Pwr", "Multiple Vitamins W Minerals Tab", "Hypo Vites Tab", "Multiple Vitamin Plus Minerals Tab", "Vc II", "One A Day Tab", "Olympian Multi Vit Plus Minerals Tab", "Vitaplex", "Hemarexin Tab", "One Daily Vitamin and Mineral Dietary Supplement", "One A Day Multiple Vit W Minerals", "Premium Prenatal", "Right Choice P.M. Multi Formula - Caplet", "Multiple Vitamins and Minerals Tab", "Swical-energy 3e Age", "Milltrium Senior Vitamin and Mineral Supplement", "C. Vit-min Formula", "Natelle One", "NESTABS ABC Prenatal Multi-vitamin/Mineral Supplement with DHA/EPA", "O-Cal FA multivitamin", "VIL-Rx", "Folgard", "Nexa Plus", "M-Natal Plus", "Vitafol-OB Plus DHA Prenatal Supplement Plus DHA", "Cal/mag+d", "Hi Potency Multi Tab", "Maxine Vitamin and Mineral Supplement", "Mag/cal 1:1 Capsules W Vitamin D", "Calcium Magnesium Avec Vitamine D Et Zinc", "Swiss One Multivitamin and Mineral Caplet", "Vege Swiss One Multivitamin W Chel Mins Tab", "Liquid Opti-minplex +d", "Acti-cal/mag 2:1 + Zinc and D Caplet", "Mor-vites Tab", "Rocky Mountain Multiple Vit and Min Mega Tab", "Extra Once A Day", "Opti-cal Chewable +d Caplet", "Ultimate Tab", "A-D Calcium Cap", "Multiminerals", "T-PA Cap", "Multi-mins Minerals", "Calcium Et Magnesium Plus Vitamine D/fe/zn", "Multi Flow Tablets", "Fusion Activator Formula Tab", "Fusion PM Formula Tab", "Calcium With Mg Zn Mn Cu CR Si and Vit. C & D", "Paramettes Adults", "Maximum Once A Day", "Liquid Calcium Mg Phosphorus and Vit.d-3", "Osteo Formula Tab", "Innersource Tab", "Prenatal Formula Tab", "Timed Release Vita-vim Srt", "Astral C Tab", "Card-floe II Tab", "Avon Vitadvance Multi-kids Complete", "Liquid Calcium and Magnesium With Vit.d", "Super Vita Vim Multivitamins and Minerals", "Natural Source Spectrum With Beta Carotene", "Chelated Cal-mag(2:1)with Zn Vit.c and D", "Vitality Brand Calcium Plus Tab", "Osteo Tablets", "Calcium Magnesium 1000/500 - Tab", "Calcium Magnesium Sulfur Silicon - Tab", "Calcium A D", "Total Living Concepts Formula One - Tab", "Total Living Concepts Formula One - Tab", "Twin Opti Pwr", "Cal Mag Plus - Tab", "Twin G.F. Powder", "Twin G.F. Powder Vanilla Flavor", "Twin G.F. Powder", "Only One - Tablet", "Vita Vim Multivitamins and Minerals Tab", "Mega-vim 75 With Beta-carotene - Tablets", "Mega-vim 75 With Beta-carotene - Tablets", "Swical D-M - Tab", "Prenatal Vi-min", "Multiple Minerals", "Anaplex Tab", "Grand Master Formula Tab", "Ad & Calcium Cap", "Multiple Mineral Liquid", "Ad Calcium Cap", "A D Calcium Tab", "Mega Capsules", "Vitalife - Capsule", "Multi Spectrum - Tablet", "24 Multivitamins + Minerals", "Calcitol", "Vitamin C W Chelates Tab", "H.W. Children's Chewable Multi Vit & Mineral", "Cal/mag 1:1 With Zinc and Vitamin D - Tablet", "Calcium 400 With Magnesium - Pwr", "Tri-mins - Cap", "Vimeral Tab", "Vimeral Tab", "Complete One-A-day - Tab", "A/o-26 - Caplet", "Usana Multimineral Tablets - Tab", "Usana Calmag Plus Tablets - Tab", "Multi Rol", "Phytofortis + Calcium A-D", "Calcium Chelate Plus Vit D", "Calcium Et Magnesium Tab", "Calci A and D Tab", "Women's Change Formula", "For-2", "Maxum Multi-vite", "Usana Multimineral Tablets", "Vita-vim - Tab", "Super Vita-vim With Beta-carotene - Tab", "Enviroflex - Tab", "Chewable Cal-mag Chocolate Flavour", "Timed Release and Esterified Vitamin C-500", "Envirocomplex", "Swical-multi", "Doctor's Choice Brand for Men", "Osteoligo", "Usana Optimizer Actical Plus Calcium-magnesium-vitamin D3-silicon Tablets", "Cal/mag 2:1 With D", "Multi #2", "Port A Mins Super Cal-mag 300/150 With Vitamin D3", "Port A Mins Super Calcium 375 With Vitamin D3", "Port A Mins Super Calcium 750 With Vitamin D3", "Port A Mins Super Cal-mag 600/300", "Century Complete", "Central-vite 18 Essential", "Swiss One", "Formula Osg", "Multi Cal Mag Liquid", "Formula A.R.-th Dietary Supplement", "Mega Multiple Minerals", "Chewable Calcium Plus Magnesium and Minerals", "Children's Chewable Multivitamins and Minerals", "Osteo-force", "Cell-wise", "Multivitamines Et Mineraux Reguliers / Regular Multivitamins and Minerals", "Isotonix Calcium Plus Formula", "Calplus", "Nutri-chem Cal Mag", "Calcium and Magnesium 1:1 Plus Tablets", "Calcimag Tab", "Cell-wise Natural Source", "Complete Multivitamins and Minerals Tablets Timed Release", "Calcium Phosphorus & Vitamin D", "Tropicana Calcium and Vitamin C Supplement", "Mineral Support", "Calcium & Magnesium Citrate Plus D With Manganese, Potassium & Zinc", "Calcium & Magnesium Plus Potassium & Zinc", "Vitamin & Mineral Formula 1 Dietary Supplement", "Osteo-life", "L.G.I.T.", "A.R.T.H. Away Formula", "Calcium/magnesium Drink", "Osteo Formula", "Multiple Vitamins With Minerals Tablets", "Super Kids Chewable Multivitamin Multimineral (chewable Tablets)", "Actical Plus Calcium-magnesium-vitamin D3-silicon Chewable", "Supplements De Vitamines Et Mineraux", "Chelated Cal/mag/zn With Vitamins", "C.H.V. Formula", "Multivitamins and Minerals - Complete", "Children's Chewable Multi-vitamin Complete With Minerals", "Multi Vitamins & Minerals", "Formula Inf", "Formula Int", "Classic Swiss One 10 Multivitamin and Mineral Tab", "Calcium & Magnesium Plus Potassium, Zinc, & Manganese", "Calcium & Magnesium Citrate Plus D With Manganese, Potassium & Zinc", "Multi-vitamins With Minerals", "Multra Plex", "Formula O-care Vitamin and Mineral Supplement", "Luna Vitamin and Mineral Bar for Women", "Chewable Calcium & Magnesium 2:1 Tablet", "Calcium & Magnesium With Potassium & Zinc", "Calcium & Magnesium With Potassium, Zinc, Manganese & Vitamin D", "Cal-mag With Zinc & Vitamin D", "Osteo Formula", "Tropicana Calcium & Vitamin C Supplement", "Multivitamins and Minerals for Men", "Multivitamins and Minerals for Women", "Osteo Factors", "Calcium & Magnesium Plus Potassium & Zinc", "Multra With Iron", "Senior Multi One", "Multitabs", "Multipack II", "Multimineral Chelates", "Chewable Adult Multivitamins With Minerals", "Multicaps", "Children's Chewable Multivitamins With Minerals", "Men's", "Men's 50+", "Multimineral Tablets", "Multivitamins and Multiminerals Formula Regular Tablet", "One A Day Advance Adults 50+", "Bseltzer", "Nutri-chem Calcium Magnesium With D and Zinc", "Osteo Formula", "Children's Chewable Multivitamin Complete With Minerals", "Multivitamins and Minerals With Betacarotene Tablets", "One A Day Advance Adults", "Multi Vitamin & Minerals", "Essential Vitamins and Minerals", "Super Multi", "Adult Formula 50+", "Calcium With Vitamin D 200 Mg/160 Iu", "Super Cal Mag Plus", "Active Calcium Plus Magnesium, Vitamin D and Silicon", "Multi Tabs", "Magnacal", "Premel", "Hsn Formula", "Multivitamin & Minerals (iron Free)", "Cal Mag Drink With Vitamin C", "Multivitamin & Multimineral", "Osteo Regime", "Nutrilite Double X", "Nutrilite Double X", "Nutrilite Double X", "50 Plus Multiple Vitamins & Minerals", "Chewable Children's Complete Multivitamins With Essential Minerals", "Calcium Capsules With Magnesium and Vitamin D", "Spectrum Performa Multivitamins and Minerals Tablets", "Multi Mega Minerals With Vitamin D", "Body Rox", "Swiss Total One", "Multivitamins and Minerals Tablets", "Calcium & Magnesium Plus Potassium & Zinc", "Chela Calmag-300 Plus Zinc D3", "Swiss One Multi Vit & Chel Min Tab", "Chela Calmag-100 Plus Zinc D3", "Vege 1 Daily Tab", "Prevencal 300 + D A Croquer", "Chelated Calcium and Magnesium Tab", "Fem Time Tab", "Chelamins Plus Tab", "Maintain Multiple Vitamin & Minerals", "Revitex Ampoules Et Comprimes", "Multi II IV Vi Tab", "Spectrum 2 Cap", "Spd Tab", "Cal & Mag Hvp Chel Plus C Potass & Zinc Tab", "Men's Biomultiple Vitamin and Mineral Supplement", "Women's Biomultiple Vitamin and Mineral Supplement", "Complete One A Day Tab", "Nitro Vites - Tab", "Multi Plex I - Tab", "Multi Plex II - Tab", "Mega Plex III - Pck", "Mega Plex III - Pck", "Mega Plex IV - Pck", "Mega Plex IV - Pck", "K.L. Vitamin-mineral", "Nutra-clear", "Swical Extra-fort", "Nutra Boost", "Cal-mag Citrate Zinc & Vitamin D Tablets", "Hvp Chelated Cal/mag With Zinc and Vitamins C and D", "Osteoshield", "Multi-actin", "Calcor", "Alkadrenergy Tablets", "Calcium Complex High Grade", "Vita Balance 2000", "Vitaflex Dietary Suplement", "B & J Formula Dietary Supplement", "Mnps Formula Supplement", "V & M Vitamin and Mineral Supplement", "Osteo Formula", "Liquid Calcium With Vitamin D", "Tianshi Vital Powder III", "Tianshi Vital Powder II", "Tianshi Vital Powder I", "Tianshi Calcium With Natural Source Vitamin D Tablets", "Advanced B & T Formula", "Kanga-V Multivitamins & Minerals", "Global Vigen Recare Calcium", "Protect Plus SO 60", "M-Natal Plus", "M-Natal Plus" ]

[ "Q13936", "P98194", "P02585", "P63316", "Q01082", "P04271", "P20810", "P49747", "P19801", "Q99584", "P05187", "P05109", "P06702", "P29034", "P00450", "P12644", "P08493", "Q8TAB3", "O75340", "P0DP23", "P0DP24", "P0DP25" ]

[]

DB00002

Cetuximab

Cetuximab is a recombinant chimeric human/mouse IgG1 monoclonal antibody that competitively binds to epidermal growth factor receptor (EGFR) and competitively inhibits the binding of epidermal growth factor (EGF).[A227973] EGFR is a member of the ErbB family of receptor tyrosine kinases found in both normal and tumour cells; it is responsible for regulating epithelial tissue development and homeostasis.[A228083] EGFR has been implicated in various types of cancer, as it is often overexpressed in malignant cells [A227973] and EGFR overexpression has been linked to more advanced disease and poor prognosis.[A227963] EGFR is often mutated in certain types of cancer and serves as a driver of tumorigenesis.[A228083] _In vitro_, cetuximab was shown to mediate anti-tumour effects in numerous cancer cell lines and human tumour xenografts.[A227963] Approved by the FDA in February 2004 under the brand name ERBITUX, cetuximab is used for the treatment of head and neck cancer and metastatic, KRAS wild-type colorectal cancer, and metastatic colorectal cancer with a BRAF V600E mutation.[A227963,L39045] It has also been investigated in advanced colorectal cancer, EGFR-expressing non-small cell lung cancer (NSCLC), and unresectable squamous cell skin cancer.[L31418] Cetuximab is administered via intravenous infusion and is used as monotherapy or in combination with other chemotherapies, including platinum agents, radiation therapy, [leucovorin], [fluorouracil], and [irinotecan].[L30448]

liquid

Cetuximab indicated for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy. It is indicated for treating a recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with fluorouracil. It is indicated for recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.[L30448] Cetuximab is also indicated for K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer as determined by an FDA-approved test in combination with FOLFIRI, a chemotherapy combination that includes [leucovorin], [fluorouracil], and [irinotecan]; in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy; or as monotherapy in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan.[L30448] Additionally, cetuximab is also indicated for metastatic colorectal cancer that is BRAF V600E mutation-positive (as determined by an FDA-approved test) in combination with [encorafenib] but only after prior therapy.[L39045] Cetuximab is not indicated for the treatment of Ras-mutant colorectal cancer or when the results of the Ras mutation tests are unknown.[L30448]

Cetuximab is an anticancer agent that works by inhibiting the growth and survival of epidermal growth factor receptor (EGFR)-expressing tumour cells with high specificity and higher affinity than epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α), which are natural ligands of EGFR.[L31418] Cetuximab works by inhibiting the growth and survival of EGFR-positive tumours.[A227963] _In vitro_, it promotes antibody-dependent cellular cytotoxicity (ADCC) against certain human tumour types. On the contrary, cetuximab does not exert its anti-tumour effects on human tumour xenografts lacking EGFR expression.[A227963, L30448] Cetuximab potentiates the cytotoxic effects of chemotherapeutics and radiation therapy when used in combination.[L30448] In human tumour xenograft models in mice, cetuximab and irinotecan synergistically inhibited the growth of orthotopic anaplastic thyroid carcinoma xenografts _in vitro_ and _in vivo_. Cetuximab potentiated the _in vitro_ anti-proliferative and pro-apoptotic effect of irinotecan and achieved 93% _in vivo_ inhibition of tumour growth when combined with irinotecan, compared to 77% and 79% inhibition when cetuximab and irinotecan were used alone, respectively.[A227978]

The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein and a type I receptor tyrosine kinase expressed on both normal and malignant cells. It has been investigated as a therapeutic target for anticancer treatment, as it is often upregulated in cancer types, including head and neck, colon, and rectal cancers.[L30448] When activated by its ligand, EGFR undergoes a conformational change and dimerization to form homodimers or heterodimers with another member of the ErbB family of receptors. Dimerization of EGFR activates the intracellular tyrosine kinase region of EGFR and promotes autophosphorylation, initiating a series of downstream signalling cascades, including cell differentiation, proliferation, migration, angiogenesis, and apoptosis. This EGFR signalling pathway is often dysregulated in cancer cells, leading to aberrant cell growth and enhanced cell survival.[L31418] Cetuximab is a monoclonal antibody that binds specifically to the EGFR on both normal and tumour cells to competitively inhibit the binding of epidermal growth factor (EGF) and other ligands that are produced by normal and tumour tissue epithelial cells.[A11, L30448] Upon binding to domain III of EGFR - which is the binding site for its growth factor ligands - cetuximab prevents the receptor from adopting an extended conformation and thereby inhibits EGFR activation, as well as phosphorylation and activation of receptor-associated kinases (MAPK, PI3K/Akt, Jak/Stat).[A11, A228078] Inhibition of the EGFR signalling pathway ultimately leads to inhibition of cell cycle progression, cell survival pathways, and tumour cell motility and invasion.[A227963] Cetuximab also induces cell apoptosis and decreases matrix metalloproteinase and vascular endothelial growth factor (VEGF) production.[A228078, L30448] _In vitro_, cetuximab was shown to inhibit tumour angiogenesis.[A227978] Binding of cetuximab to EGFR also results in internalization of the antibody-receptor complex, leading to an overall downregulation of EGFR expression.[A227973] K-ras is a small G-protein downstream of EGFR that plays an important role in promoting the EGFR signalling cascade: in some malignant cells, K-ras can acquire activating mutations in exon 2 [L31418] and thus be continuously active regardless of EGFR regulation.[L30448] Since mutant Ras proteins can isolate the pathway from the effect of EGFR, K-Ras mutations can render EGFR inhibitors like cetuximab ineffective in exerting anti-tumour effects.[L30448, L31418] Cetuximab is thus only limited in its use for K-Ras wild-type, EGFR-expressing cancers.[L30448]

After administration of a 400 mg/m2 initial dose followed by a 250 mg/m2 weekly dose, the steady-state levels of cetuximab was reached by the third weekly infusion with mean peak and trough concentrations across studies ranging from 168 µg/mL to 235 µg/mL and 41 µg/mL to 85 µg/mL, respectively.[L30448] Tmax is about 3 hours.[A227963]

Like other monoclonal antibodies, cetuximab is expected to undergo lysosomal degradation by the reticuloendothelial system and protein catabolism by a target‐mediated disposition pathway.[A40006]

The intravenous LD50 is > 300 mg/kg in mice and > 200 mg/kg in rats.[L31408] There is limited information on the overdose from cetuximab. In clinical trials, cetuximab was associated with serious and fatal infusion reactions, cardiopulmonary arrest or sudden death, and serious dermatologic toxicities. Pulmonary toxicities, such as interstitial lung disease, interstitial pneumonitis with non-cardiogenic pulmonary edema, and exacerbation of pre-existing fibrotic lung disease have been reported.[L30448]

After administration of a 400 mg/m2 initial dose followed by a 250 mg/m2 weekly dose, the mean half-life for cetuximab was approximately 112 hours, with a range of 63 to 230 hours.[L30448]

There is no information available.

There is limited information available.

The volume of the distribution is about 2-3 L/m2 and is independent of dose.[L30448]

In patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck, the estimated clearance rate was 0.103 L/h.[A228003] At doses ranging from 200 to 400 mg/m2, complete saturation of systemic clearance was observed. In a population pharmacokinetic study, female patients had a 25% lower intrinsic cetuximab clearance than male patients, although there was no evidence of the need for dose modification based on sex.[A227963]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "L01FE", "L01F", "L01", "L" ]

[ "Humans and other mammals" ]

[]

[ { "approved": "1999-03-02", "country": "Canada", "expires": "2016-03-02", "number": "1340417" } ]

[ "Erbitux", "Erbitux", "Erbitux", "Erbitux", "Erbitux" ]

[]

[ "P00533", "O75015", "P02745", "P02746", "P02747", "P08637", "P12314", "P12318" ]

[]

DB00003

Dornase alfa

Dornase alfa is a biosynthetic form of human deoxyribunuclease I (DNase I) enzyme. It is produced in genetically modified Chinese hamster ovary (CHO) cells using recombinant DNA technology. The 260-amino acid sequence of dornase alfa is identical to the endogenous human enzyme. Dornase alfa cleaves extracellular DNA to 5´-phosphodinucleotide and 5´-phosphooligonucleotide end products without affecting intracellular DNA. In individuals with cystic fibrosis, extracellular DNA, which is an extremely viscous anion, is released by degenerating leukocytes that accumulate during inflammatory responses to infections. Enzymatic breakdown of this extracellular DNA appears to reduce sputum viscosity and viscoelasticity.

liquid

Used as adjunct therapy in the treatment of cystic fibrosis.

Cystic fibrosis (CF) is a disease characterized by the retention of viscous purulent secretions in the airways. These thick secretions contribute both to reduced pulmonary function and to frequent pulmonary infection. Purulent pulmonary secretions of individuals with cystic fibrosis contain very high concentrations of extracellular DNA released by degenerating leukocytes that accumulate in response to these infections. Dornase alfa hydrolyzes the DNA in sputum of CF patients and reduces sputum viscosity and viscoelasticity. The enzyme does not appear to affect sputum in the absence of an inflammatory response to infection, nor does it affect the sputum of healthy individuals.

Dornase alfa is a biosynthetic form of human DNase I. The enzyme is involved in endonucleolytic cleavage of extracellular DNA to 5´-phosphodinucleotide and 5´-phosphooligonucleotide end products. It has no effect on intracellular DNA. Optimal activity is dependent on the presence of divalent cations such as calcium and magnesium. Extracellular DNA is a viscous anionic polymer and its breakdown appears to improve the viscosity and viscoelasticity of purulent sputum of individuals with CF, thus reducing airflow obstruction. Dornase alfa does not seem to have any effect on non-purulent sputum.

Studies in rats and monkeys after inhalation of dornase alfa shows very little systemic absorption (less than 15% for rats and less than 2% for monkeys). The results were also witnessed in patients. Dornase alfa is also associated with very low accumulation with no serum concentration greater than 10ng/mL observed no matter the dose administered. Bioavailability: mean sputum concentrations of dornase alfa can be measured after 15 minutes. Onset is achieved within 3 to 7 days. Peak concentrations are achieved after 9 days.

While no conclusive studies have yet been published, dornase alfa is expected to be metabolized by proteases in biofluids.

Adverse reactions occur at a frequency of < 1/1000 and are usually mild and transient in nature. Reported adverse effects include chest pain (pleuritic/non-cardiac), fever, dyspepsia, voice alteration (hoarseness), pharyngitis, dyspnea, laryngitis, rhinitis, decreased lung function, rash, urticaria, and conjunctivitis. There is no evidence of carcinogenic or mutagenic properties. The safety of dornase alfa has not been studied in pregnant women, nursing women and children under the age of 5 years old.

null

In studies in rats and monkeys, the initial volume of distribution is similar to the serum volume. Concentrations in sputum decline rapidly after inhalation.

Studies in rats indicate that, following aerosol administration, the disappearance half-life of dornase alfa from the lungs is 11 hours. In humans, sputum DNase levels declined below half of those detected immediately post-administration within 2 hours but effects on sputum rheology persisted beyond 12 hours.

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "R05CB", "R05C", "R05", "R" ]

[ "Humans and other mammals" ]

[ { "cost": "3.21", "description": "Lufyllin 200 mg tablet", "unit": "tablet" }, { "cost": "3.84", "description": "Lufyllin-gg tablet", "unit": "tablet" }, { "cost": "3.99", "description": "Lufyllin-GG 200-200 mg tablet", "unit": "tablet" }, { "cost": "4.62", "description": "Lufyllin-400 tablet", "unit": "tablet" }, { "cost": "4.81", "description": "Lufyllin 400 mg tablet", "unit": "tablet" }, { "cost": "37.05", "description": "Pulmozyme 1 mg/ml ampul", "unit": "ml" }, { "cost": "77.06", "description": "Pulmozyme 1 mg/ml Solution 2.5ml Plastic Container", "unit": "plastic" }, { "cost": "0.6", "description": "Lufyllin-GG 100-100 mg/15ml Elixir", "unit": "ml" } ]

[ { "approved": "2005-02-22", "country": "Canada", "expires": "2015-02-28", "number": "2184581" }, { "approved": "2004-10-26", "country": "Canada", "expires": "2013-05-28", "number": "2137237" } ]

[ "Pulmozyme", "Pulmozyme" ]

[ "Viscozyme" ]

[]

[ "P24855" ]

[]

DB00004

Denileukin diftitox

Denileukin diftitox is an IL2-receptor-directed cytotoxin, is a recombinant DNA-derived fusion protein composed of the amino acid sequences for diphtheria toxin fragments A and B (Met1-Thr387)-His and the sequence for human interleukin-2 (IL-2; Ala1-Thr133).[L51254] It is designed to deliver diphtheria toxin into IL-2 receptor-expressing cancer cells to cause cell death.[A264349, L51254] Denileukin diftitox was originally approved by the FDA in 1999 for the treatment of cutaneous T-cell lymphoma (CTCL),[A264339, L51264] making it the first fusion protein cytotoxin approved to treat a human disease in the US.[A264344] In 2014, it was withdrawn voluntarily from the market due to manufacturing issues; however, the biologics license application (BLA) for denileukin diftitox was resubmitted, and it was approved on August 8, 2024.[L51264]

liquid

Denileukin diftitox was previously indicated for the treatment of adult patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL) whose malignant cells express the CD25 component of the IL-2 receptor.[L26381] It is also indicated for the treatment of adult patients with relapsed or refractory Stage I-III CTCL after at least one prior systemic therapy.[L51254]

Denileukin diftitox is an anticancer drug with cytocidal actions on cancer cells.[L51254] Denileukin diftitox demonstrated the ability to deplete immunosuppressive regulatory T lymphocytes (Tregs) and antitumor activity through direct cytocidal action on IL-2R-expressing tumours.[L51254]

Denileukin diftitox is a fusion protein composed of truncated diphtheria toxin (DT), which is a cytocidal moiety, and the full-length sequence of interleukin-2 (IL-2), which acts as a ligand for the IL-2 receptor.[A264344] Denileukin diftitox is reported to bind to a high- or intermediate-affinity receptor.[A264344] Once the drug molecule binds to the IL-2 receptor, denileukin diftitox is internalized via receptor-mediated endocytosis in an acidified vesicle.[A15, A264344] After uptake into the cell, denileukin diftitox is proteolytically cleaved within the endosomes to release the enzymatically active portion of the DT. DT is translocated across the endosomal membrane into the cytosol to inhibit protein synthesis via ADP-ribosylation of elongation factor-2, ultimately resulting in cell death. The fragment of DT is translocated across the endosomal membrane into the cytosol where it inhibits protein synthesis via ADP-ribosylation of elongation factor-2, resulting in cell death.[A264344, L51254]

Following a single dose of denileukin diftitox 9 mcg/kg via one-hour infusion in patients with CTCL, the geometric mean (coefficient of variation [CV]%) maximum serum concentration (Cmax) was 94.4 ng/mL (77%) and area under the concentration over time curve (AUC0-inf) was 20700 ng x min/L (60%) on the first day of the first administration cycle. There is no accumulation after repeated daily dosing.[L51254]

Denileukin diftitox is expected to be metabolized into small peptides by catabolic pathways.[L51254]

There is limited information regarding the acute toxicity (LD50) and overdose of denileukin diftitox.

The arithmetic mean (CV%) denileukin diftitox terminal half-life is 112 minutes (31%) on the first day of the first cycle.[L51254]

null

The geometric mean (CV%) volume of distribution of denileukin diftitox is 5.0 L (43%) on the first day of the first administration cycle.[L51254]

The geometric mean (CV%) clearance is 36.5 mL/min (73%) after the first dose of denileukin diftitox at the recommended dose level.[L51254]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L01XX", "L01X", "L01", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "878.4", "description": "Ontak 150 mcg/ml vial", "unit": "ml" } ]

[]

[ "Ontak" ]

[]

[ "P01589", "P14784" ]

[]

DB00005

Etanercept

Dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kilodalton (p75) tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1.[L14862,A216522] The Fc component of etanercept contains the CH2 domain, the CH3 domain and hinge region, but not the CH1 domain of IgG1. Etanercept is produced by recombinant DNA technology in a Chinese hamster ovary (CHO) mammalian cell expression system. It consists of 934 amino acids. It is used to treat or manage a variety of inflammatory conditions including rheumatoid arthritis (RA), ankylosing spondylitis (AS), and juvenile idiopathic poly-articular arthritis (JIA).

liquid

Etanercept is indicated for the treatment of moderately to severely active rheumatoid arthritis in adults and in chronic moderate to severe plaque psoriasis in patients 4 years of age and older.[L14862,L45523] It is also used to manage signs and symptoms of polyarticular idiopathic arthritis and Juvenile Psoriatic Arthritis in those aged 2 years and older. Etanercept is also used to manage the symptoms of psoriatic arthritis and ankylosing spondylitis.[L48526]

Etanercept binds specifically to tumor necrosis factor (TNF) and thereby modulates biological processes that are induced or regulated by TNF.[L14862,A216522] Such processes or molecules affected include the level of adhesion molecules expressed, as well as serum levels of cytokines and matrix metalloproteinases.

There are two distinct receptors for TNF (TNFRs), a 55 kilodalton protein (p55) and a 75 kilodalton protein (p75). The biological activity of TNF is dependent upon binding to either cell surface receptor (p75 or p55).[A216522] Etanercept is a dimeric soluble form of the p75 TNF receptor that can bind to two TNF molecules, thereby effectively removing them from circulation. Notably, etancerpt is only capable of binding to the active trimeric form of TNF as its binding site is located in the cleft between subunits.[A77626]TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses.[A216522] Increased levels of TNF are found in tissues and fluids of those with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis.

Population pharmacokinetic modeling in adults with RA, AS, or who were healthy showed a subcutaneous bioavailability of 56.9% with a Ka of 0.0223/h.[A215352] Another model in pediatric JIA patients showed an increased Ka of 0.05/h with a high mean interindividual variability of 215%.[A215357] Cmax after a single 25 mg subcutaneous dose of Enbrel is reported as 1.1 mcg/L with a Tmax of 69 h.[L14862] Cmax after repeated dosing is reported as 2.4 mcg/L in adult RA patients with a dosage of 25 mg twice weekly and 2.1 mcg in pediatric JIA patients with a dosage of 0.4 mg/kg twice weekly.

As etanercept is a fusion protein antibody, it is assumed to be metabolized via proteinases similarly to endogenous proteins.

null

Etanercept has a mean half-life of elimination of 102 hours in RA patients.[L14862] Population models have shown a mean half-life of 68 hours in healthy adults and 70.7-94.8 hours in pediatric JIA patients.[A215657,A215357]

No significant protein binding has been identified.

null

Population pharmacokinetic modeling predicts a total Vd of 5.49 L with a peripheral compartment of 1.24 L in adults with RA and an apparent Vd with subcutaneous administration in pediatric JIA patients of 7.88 L.[A215352,A215357]

Etanercept has a mean apparent clearance of 160 mL/h in RA patients.[L14862] Population models predict a mean apparent clearance of 132 mL/h in healthy adults and 0.0576 L/h in pediatric JIA patients.[A215657,A215357]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L04AB", "L04A", "L04", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "250.37", "description": "Enbrel 25 mg kit", "unit": "each" }, { "cost": "488.74", "description": "Enbrel 50 mg/ml sureclick syr", "unit": "syringe" }, { "cost": "1016.57", "description": "Enbrel 4 25 mg Kit (1 Box = 1 Kit = Four 25 mg Vials)", "unit": "box" }, { "cost": "2033.14", "description": "Enbrel (1 Box = 1 Kit = Four 50 mg Syringes) 3.92ml Box", "unit": "box" }, { "cost": "2033.14", "description": "Enbrel SureClick (1 Box Contains Four 50 mg Prefilled Autoinjectors)", "unit": "box" } ]

[ { "approved": "2009-06-16", "country": "Canada", "expires": "2023-02-27", "number": "2476934" }, { "approved": "2000-03-14", "country": "Canada", "expires": "2013-09-14", "number": "2123593" }, { "approved": "2007-10-02", "country": "United States", "expires": "2024-07-29", "number": "7276477" } ]

[ "Benepali", "Benepali", "Benepali", "Benepali", "Benepali", "Benepali", "Benepali", "Brenzys", "Brenzys", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Enbrel", "Erelzi", "Erelzi", "Erelzi", "Erelzi", "Erelzi", "Erelzi", "Erelzi", "Erelzi", "Erelzi", "Erelzi", "Erelzi", "Erelzi", "Erelzi", "Erelzi", "Erelzi", "Erelzi", "Erelzi", "Eticovo", "Eticovo", "Nepexto", "Nepexto", "Nepexto", "Nepexto", "Nepexto", "Nepexto", "Nepexto", "Nepexto", "Rymti", "Rymti", "Rymti", "Truemed Group LLC" ]

[ "Davictrel", "Tunex" ]

[ "Enbrel", "Enbrel" ]

[ "P01375", "P01374", "P12314", "P12318", "P31994", "P31995", "P08637", "O75015", "P02745", "P02746", "P02747" ]

[]

DB00006

Bivalirudin

Bivalirudin is a synthetic 20 residue peptide (thrombin inhibitor) which reversibly inhibits thrombin. Once bound to the active site, thrombin cannot activate fibrinogen into fibrin, the crucial step in the formation of thrombus. It is administered intravenously. Because it can cause blood stagnation, it is important to monitor changes in hematocrit, activated partial thromboplastin time, international normalized ratio and blood pressure.

solid

For treatment of heparin-induced thrombocytopenia and for the prevention of thrombosis. Bivalirudin is indicated for use in patients undergoing percutaneous coronary intervention (PCI), in patients at moderate to high risk acute coronary syndromes due to unstable angina or non-ST segment elevation in whom a PCI is planned.

Bivalirudin mediates an inhibitory action on thrombin by directly and specifically binding to both the catalytic site and anion-binding exosite of circulating and clot-bound thrombin. The action of bivalirudin is reversible because thrombin will slowly cleave the thrombin-bivalirudin bond which recovers the active site of thrombin.

Inhibits the action of thrombin by binding both to its catalytic site and to its anion-binding exosite. Thrombin is a serine proteinase that plays a central role in the thrombotic process, acting to cleave fibrinogen into fibrin monomers and to activate Factor XIII to Factor XIIIa, allowing fibrin to develop a covalently cross-linked framework which stabilizes the thrombus; thrombin also activates Factors V and VIII, promoting further thrombin generation, and activates platelets, stimulating aggregation and granule release.

Following intravenous administration, bivalirudin exhibits linear pharmacokinetics. The mean steady state concentration is 12.3 +/- 1.7mcg/mL after administration of an intravenous bolus of 1mg/kg followd by a 2.5mg/kg/hr intravenous infusion given over 4 hours.

80% proteolytic cleavage

Based on a study by Gleason et al., the no-observed-adverse-effect level (NOAEL) for bivalirudin, administered to rats via intravenous infusion over a 24-hour period, was 2000 mg/kg/24 h.

* Normal renal function: 25 min (in normal conditions) * Creatinine clearance 10-29mL/min: 57min * Dialysis-dependant patients: 3.5h

Other than thrombin and red blood cells, bivalirudin does not bind to plasma proteins.

Bivalirudin is cleared from plasma by a combination of renal mechanisms (20%) and proteolytic cleavage.

0.2L/kg

* 3.4 mL/min/kg [Normal renal function] * 3.4 mL/min/kg [mild renal function] * 2.7 mL/min/kg [moderate renal function] * 2.8 mL/min/kg [severe renal function] * 1 mL/min/kg [Dialysis-dependent patients]

Organic compounds

Organic Polymers

Polypeptides

null

[ "approved", "investigational" ]

[ "B01AE", "B01A", "B01", "B" ]

[ "Humans and other mammals" ]

[ { "cost": "780.0", "description": "Angiomax 250 mg vial", "unit": "vial" } ]

[ { "approved": "1993-03-23", "country": "United States", "expires": "2010-05-23", "number": "5196404" }, { "approved": "1999-12-14", "country": "Canada", "expires": "2010-08-17", "number": "2065150" }, { "approved": "2009-10-06", "country": "United States", "expires": "2029-01-27", "number": "7598343" }, { "approved": "2009-09-01", "country": "United States", "expires": "2029-01-27", "number": "7582727" }, { "approved": "2019-05-20", "country": "United States", "expires": "2039-05-20", "number": "11903993" }, { "approved": "2019-05-20", "country": "United States", "expires": "2039-05-20", "number": "11918622" }, { "approved": "2019-05-20", "country": "United States", "expires": "2039-05-20", "number": "11992514" } ]

Bivalirudin | Bivalirudina | Bivalirudinum | 3.4.21.5 | Coagulation factor II | 1.11.2.2 | MPO

[ "Angiomax", "Angiomax", "Angiomax", "Angiomax", "Angiomax RTU", "Angiox", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin", "Bivalirudin for Injection", "Bivalirudin for Injection", "Bivalirudin for Injection", "Bivalirudin for Injection", "Bivalirudin in 0.9% Sodium Chloride", "Bivalirudin in 0.9% Sodium Chloride", "Bivalirudin Injection", "Bivalirudin RTU" ]

[ "Angiox", "Hirulog" ]

[]

[ "P00734" ]

[ "P05164" ]

[]

DB00007

Leuprolide

Leuprolide is a synthetic 9-residue peptide analogue of gonadotropin-releasing hormone (GnRH). Unlike the endogenous decapeptide GnRH, leuprolide contains a single D-amino acid (D-leucyl) residue, which helps to increase its circulating half-life from three to four minutes to approximately three hours.[A203222] As a GnRH mimic, leuprolide is capable of binding to the GnRH receptor (GnRHR) and inducing downstream modulation of both gonadotropin hormone and sex steroid levels. Prolonged activation of GnRHR results in significant downregulation of sex steroid levels, which is primarily responsible for the clinical efficacy of leuprolide in diverse conditions, including advanced prostate cancer, endometriosis, and central precocious puberty.[A203126, A203132] Leuprolide was first approved in 1985 as a daily subcutaneous injection under the tradename Lupron™ by Abbvie Endocrine Inc.[L13850] Since this initial approval, various long-acting intramuscular and subcutaneous products have been developed such that patients can be dosed once every six months.[L13781, L13790] Leuprolide remains frontline therapy in all conditions for which it is indicated for use.

solid

Leuprolide is indicated for the treatment of advanced prostate cancer [L13781, L34415] and as palliative treatment of advanced prostate cancer.[L13790] It is also used for the treatment of pediatric patients with central precocious puberty (CPP).[L13784, L13787] In combination with oral [norethisterone] (also known as norethindrone), leuprolide is also indicated for the initial treatment of the symptoms of endometriosis.[L10310] Finally, in combination with iron supplementation, leuprolide is indicated for the preoperative hematological improvement of anemic patients with uterine leiomyomata (uterine fibroids).[L13814]

Leuprolide is a gonadotropin-releasing hormone (GnRH) analogue that functions as a GnRH receptor superagonist.[A203132, A203222] After an initial spike in GnRH-mediated steroidal production, including testosterone and estradiol, prolonged use results in a significant drop in circulating steroid levels, in line with those produced through other forms of androgen-deprivation therapy (ADT).[A203126, A203129, A203132] The corresponding hormonal/steroidal changes produce specific adverse effects in different patient populations. In women undergoing treatment for endometriosis or uterine leiomyomata, careful consideration regarding pregnancy status is advised. The initial increase in estradiol levels may worsen symptoms such as pain and bleeding. Long-term use of leuprolide is associated with loss of bone mineral density. Patients co-administered with [norethisterone] may experience sudden vision loss, proptosis, diplopia, migraine, thrombophlebitis, and pulmonary embolism and may also be at higher risk of cardiovascular disease. Patients with a history of depression may experience severe recurrence of depressive symptoms.[L10310, L13814] In men undergoing palliative treatment for advanced/metastatic prostate cancer, short-term spikes in testosterone levels may cause tumour flare and associated symptoms such as bone pain, hematuria, neuropathy, bladder and/or ureteral obstruction, and spinal cord compression. In addition, patients are at increased risk of developing hyperglycemia, diabetes, and cardiovascular disease, which may manifest through myocardial infarction, stroke, cardiac death, or prolonged QT/QTc interval. In addition, Leuprolide may cause convulsions and embryo-fetal toxicity.[L13781, L13790] In pediatric patients undergoing treatment for central precocious puberty (CPP), the initial steroidal spike may be associated with increased clinical signs of puberty within 2-4 weeks of treatment initiation. In addition, leuprolide may cause convulsions and psychiatric symptoms, including irritability, impatience, aggression, anger, and crying.[L13784, L13787]

Gonadotropin-releasing hormone (GnRH) is a naturally occurring decapeptide that modulates the hypothalamic-pituitary-gonadal (HPG) axis. GnRH binds to corresponding receptors (GnRHRs) on the anterior pituitary gonadotropes, which in turn release luteinizing hormone (LH) and follicle-stimulating hormone (FSH); these, in turn, affect the downstream synthesis and release of the sex hormones testosterone, dihydrotestosterone, estrone, and estradiol.[A203126, A203132] Despite the variety of conditions indicated for treatment with leuprolide, the mechanism of action underlying efficacy is the same in all cases. As a GnRHR agonist, leuprolide binds to and initially activates downstream LH and FSH release; this initial spike in gonadotropin levels is responsible for some of the adverse effects associated with treatment. After 2-4 weeks of treatment, continuous stimulation of GnRHR results in feedback inhibition and significant downregulation of LH, FSH, and their corresponding downstream effects, producing a therapeutic benefit. These effects are reversible upon treatment discontinuation.[A203126, A203129, A203132, A203222, L10310, L13781, L13784, L13787, L13790, L13814]

Leuprolide is typically administered as a single-dose long-acting formulation employing either microsphere or biodegradable solid depot technologies.[A203126] Regardless of the exact formulation and initial dose strength, the Cmax is typically achieved by 4-5 hours post-injection and displays large variability in the range of 4.6 - 212 ng/mL. Eventual steady-state kinetics are typically achieved by four weeks, with a narrower range of 0.1 - 2 ng/mL. No studies on the effects of food on absorption have been carried out.[L10310, L13781, L13784, L13787, L13790, L13814, L34415]

Radiolabeling studies suggest that leuprolide is primarily metabolized to inactive penta-, tri-, and dipeptide entities, which are likely further metabolized. It is expected that various peptidases encountered throughout systemic circulation are responsible for leuprolide metabolism.[L10310, L13781, L13784, L13787, L13790, L13814, L34415]

Leuprolide is considered extremely safe, with low dose-related toxicity and comparatively mild adverse effects.[A203126] Prostate cancer patients treated with leuprolide at doses as high as 20 mg/day for two years showed no additional adverse effects compared to those receiving 1 mg/day.[L13814]

Leuprolide has a terminal elimination half-life of approximately three hours.[L10310, L13781, L13784, L13787, L13790, L13814, L34415]

Leuprolide displays _in vitro_ binding to human plasma proteins between 43% and 49%.[L10310, L13781, L13784, L13787, L13790, L13814, L34415]

Following administration of 3.75 mg leuprolide depot suspension to three patients, less than 5% of the initial dose was recovered as unchanged or pentapeptide metabolite in the urine.[L10310, L13781, L13784, L13814]

Leuprolide has an apparent steady-state volume of distribution of 27 L following intravenous bolus administration to healthy males. The volume of distribution for indicated routes of subcutaneous or intramuscular injection has not been reported.[L10310, L13781, L13784, L13787, L13790, L13814, L34415]

Leuprolide administered as a 1 mg intravenous bolus in healthy males has a mean systemic clearance between 7.6 and 8.3 L/h.[L10310, L13781, L13784, L13787, L13790, L13814, L34415]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L02AE", "L02A", "L02", "L", "L02AE", "L02A", "L02", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "385.33", "description": "Leuprolide 2wk 1 mg/0.2 ml kit", "unit": "kit" }, { "cost": "400.74", "description": "Leuprolide Acetate 1 mg/0.2ml Kit 2.8ml 2-Week Kit", "unit": "box" }, { "cost": "493.2", "description": "Eligard 7.5 mg syringe", "unit": "syringe" }, { "cost": "594.37", "description": "Lupron 2-wk 1 mg/0.2 ml kit", "unit": "kit" }, { "cost": "1479.6", "description": "Eligard 22.5 mg syringe", "unit": "syringe" }, { "cost": "1972.8", "description": "Eligard 30 mg syringe", "unit": "syringe" }, { "cost": "2959.2", "description": "Eligard 45 mg syringe", "unit": "syringe" } ]

[ { "approved": "2000-03-14", "country": "United States", "expires": "2016-12-13", "number": "6036976" }, { "approved": "2014-12-30", "country": "United States", "expires": "2031-02-05", "number": "8921326" }, { "approved": "2008-09-30", "country": "United States", "expires": "2019-01-13", "number": "7429559" }, { "approved": "2014-08-26", "country": "United States", "expires": "2022-06-28", "number": "8815801" }, { "approved": "1998-03-17", "country": "United States", "expires": "2017-01-30", "number": "5728396" }, { "approved": "2000-12-05", "country": "United States", "expires": "2017-01-30", "number": "6156331" }, { "approved": "2002-04-23", "country": "United States", "expires": "2018-12-17", "number": "6375978" }, { "approved": "2001-05-22", "country": "United States", "expires": "2017-06-13", "number": "6235712" }, { "approved": "2000-09-05", "country": "United States", "expires": "2018-07-24", "number": "6113938" }, { "approved": "2000-09-26", "country": "United States", "expires": "2017-06-13", "number": "6124261" }, { "approved": "2002-05-28", "country": "United States", "expires": "2017-01-30", "number": "6395292" }, { "approved": "2000-10-17", "country": "United States", "expires": "2017-01-30", "number": "6132420" }, { "approved": "1999-11-16", "country": "United States", "expires": "2017-01-30", "number": "5985305" }, { "approved": "1999-08-03", "country": "United States", "expires": "2017-06-13", "number": "5932547" }, { "approved": "2003-05-20", "country": "United States", "expires": "2018-10-28", "number": "6565874" }, { "approved": "2004-08-10", "country": "United States", "expires": "2018-10-28", "number": "6773714" }, { "approved": "2003-09-30", "country": "United States", "expires": "2020-03-27", "number": "6626870" }, { "approved": "2016-03-15", "country": "United States", "expires": "2018-10-28", "number": "9283282" }, { "approved": "2016-02-09", "country": "United States", "expires": "2018-10-28", "number": "9254307" }, { "approved": "2013-07-16", "country": "United States", "expires": "2018-10-28", "number": "8486455" }, { "approved": "2014-09-23", "country": "United States", "expires": "2020-11-13", "number": "8840916" }, { "approved": "2013-06-25", "country": "United States", "expires": "2023-10-15", "number": "8470359" }, { "approved": "2017-01-10", "country": "United States", "expires": "2020-11-13", "number": "9539333" }, { "approved": "2018-03-13", "country": "United States", "expires": "2020-11-13", "number": "9914802" }, { "approved": "2020-05-12", "country": "United States", "expires": "2027-01-16", "number": "10646572" }, { "approved": "2017-02-21", "country": "United States", "expires": "2027-01-16", "number": "9572857" }, { "approved": "2017-08-29", "country": "United States", "expires": "2027-01-16", "number": "9744207" }, { "approved": "2017-10-17", "country": "United States", "expires": "2020-12-15", "number": "9789064" }, { "approved": "2017-04-11", "country": "United States", "expires": "2028-03-22", "number": "9617303" }, { "approved": "2019-01-01", "country": "United States", "expires": "2039-01-01", "number": "11717555" }, { "approved": "2021-12-22", "country": "United States", "expires": "2041-12-22", "number": "11771841" }, { "approved": "2021-12-22", "country": "United States", "expires": "2041-12-22", "number": "11931559" } ]

[ "Camcevi", "Camcevi", "Camcevi", "Camcevi", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Eligard", "Fensolvi", "Fensolvi", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate Depot", "Leuprolide Acetate Injection", "Lupaneta Pack", "Lupaneta Pack", "Lupron", "Lupron", "Lupron", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot", "Lupron Depot Ped", "Lupron Depot Ped", "Lupron Depot Ped", "Lupron Depot-PED", "Lupron Depot-PED", "Lupron Depot-PED", "Lupron Depot-PED", "Lupron Depot-PED", "Lupron Depot-PED", "Lupron Depot-PED", "Viadur", "Zeulide Depot", "Zeulide Depot" ]

[ "Camcevi", "Leuplin", "LeuProMaxx", "Memryte", "Prostap 3", "Prostap SR" ]

[ "Viadur", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Lupron Depot", "Leuprolide Acetate", "Leuprolide Acetate", "Lupaneta Pack", "Lupaneta Pack", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate", "Leuprolide Acetate" ]

[ "P30968", "P01148" ]

[]

DB00008

Peginterferon alfa-2a

Peginterferon alfa-2a is a form of recombinant interferon used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [L852]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) resulting in less use of Peginterferon alfa-2a. Peginterferon alfa-2a is derived from the alfa-2a moeity of recombinant human interferon and acts by binding to human type 1 interferon receptors. Activation and dimerization of this receptor induces the body's innate antiviral response by activating the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Use of Peginterferon alfa-2a is associated with a wide range of severe adverse effects including the aggravation and development of endocrine and autoimmune disorders, retinopathies, cardiovascular and neuropsychiatric complications, and increased risk of hepatic decompensation in patients with cirrhosis. The use of Peginterferon alfa-2a has largely declined since newer interferon-free antiviral therapies have been developed. In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) no longer recommend Peginterferon alfa-2a for the treatment of Hepatitis C [A19593]. Peginterferon alfa-2a was used alongside [DB00811] with the intent to cure, or achieve a sustained virologic response (SVR), after 48 weeks of therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality [A19626]. Peginterferon alfa-2a is available as a fixed dose injector (tradename Pegasys) used for the treatment of chronic Hepatitis C. Approved in 2002 by the FDA, Pegasys is indicated for the treatment of HCV with [DB00811] or other antiviral drugs [FDA Label]. When combined together, Peginterferon alfa-2a and [DB00811] have been shown to achieve a SVR between 36% for genotype 1 and 59% for genotypes 2-6 after 48 weeks of treatment.

liquid

Peginterferon alfa-2a is indicated for the treatment of HCV in combination with other antiviral drugs in patients over 5 years of age with compensated liver disease [FDA Label]. May be used as a monotherapy in patients with contraindications to or significant intolerance to other anti-viral therapies. Peginterferon alfa-2a is also indicated as a monotherapy for adult patients with HBeAg positive and HBeAg negative chronic hepatitis B infection who have compensated liver disease and evidence of viral replication and liver inflammation [FDA Label].

Peginterferon alfa-2a induces the body's innate antiviral response [FDA Label].

Peginterferon alfa-2a is derived from recombinant human interferon's alfa-2a moeity [FDA Label]. It binds to and activates human type 1 interferon receptors causing them to dimerize. This activates the JAK/STAT pathway. Activation of the JAK/STAT pathway increases expression of multiple genes in multiple tissues involved in the innate antiviral response.

Peginterferon alfa-2a reaches peak plasma concentration 72-96 hours after subcutaneous administration [FDA Label]. Trough concentrations at week 48 are approximately 2 fold higher than week 1. The peak to trough ratio at week 48 is 2.

null

Peginterferon alfa-2a may manifest neuropsychiatric complications include suicide, suicidal ideation, homicidal ideation, depression, relapse of drug addiction, and drug overdose [FDA Label]. Hypertension, supraventricular arrhythmias, chest pain, and myocardial infarction have been observed in patients using Peginterferon alfa-2a. Peginterferon alfa-2a may produce myelosuppression as well as the development or aggravation of autoimmune disorders including myositis, hepatitis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus. Peginterferon alfa-2a causes or aggravates hypothyroidism and hyperthyroidism. Hyperglycemia, hypoglycemia, and diabetes mellitus have been observed to develop in patients treated with Peginterferon alfa-2a. Peginterferon alfa-2a may decrease or produce loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, papilledema and serous retinal detachment. Peginterferon mayy be related to increased ischemic and hemorrhagic cerebrovascular events. Patients with cirrhosis on Peginterferon alfa-2a are at risk of hepatic decompensation. Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension and sarcoidosis may be induced or aggravated by Peginterferon alfa-2a. Serious and severe infections (bacterial, viral, or fungal) have been reported during treatment with Peginterferon alfa-2a. Ulcerative and hemorrhagic/ischemic colitis have been observed within 12 weeks of starting Peginterferon alfa-2a treatment. Pancreatitis and peripheral nephropathy have also been reported. Peginterferon alfa-2a is associated with growth inhibition in pediatric patients. Use of Peginterferon alfa-2a while pregant may result in delopmental abnormalities or death of the fetus.

The mean terminal half-life of peginterferon alfa-2a is 164 in a range of 84-353 hours [FDA Label].

null

The mean systemic clearance of peginterferon alfa-2a is 94 milliliters per hour [FDA Label].

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L03AB", "L03A", "L03", "L", "L03AB", "L03A", "L03", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "642.64", "description": "Pegasys 180 mcg/ml vial", "unit": "ml" }, { "cost": "2533.2", "description": "Pegasys 180 mcg/0.5 ml conv.pk", "unit": "each" }, { "cost": "2634.53", "description": "Pegasys (1 Kit = Four 180 mcg/ml Vials Prefilled Syringes) Box", "unit": "box" } ]

[ { "approved": "2009-06-30", "country": "Canada", "expires": "2017-04-23", "number": "2203480" }, { "approved": "2000-10-03", "country": "Canada", "expires": "2016-03-26", "number": "2172664" } ]

[ "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys", "Pegasys Rbv", "Pegasys Rbv" ]

[]

[ "Pegasys Rbv", "Pegasys Rbv" ]

[ "P48551", "P17181" ]

[ "P05177" ]

[]

DB00009

Alteplase

Alteplase is a recombinant tissue plasminogen activator (rt-PA) used as a thrombolytic agent.[L43125] It cleaves plasminogen to form plasmin, an enzyme involved in the degradation of fibrin clots. In the absence of fibrin, the alteplase-mediated conversion of plasminogen is limited, thanks to the high affinity between alteplase and fibrin.[A252330,L43125] Alteplase is a purified glycoprotein of 527 amino acids expressed in Chinese hamster ovary (CHO) cells.[A252345,L43125] It was first approved by the FDA in 1987 for the management of thromboembolic disease, including acute myocardial infarction (AMI).[A252270] The use of alteplase to manage AMI has decreased thanks to the availability of safer treatments such as angioplasty and stenting. However, its use for the treatment of acute ischemic stroke (AIS) has increased over the years.[A252340] New thrombolytic agents derived from tissue plasminogen activator, such as [desmoteplase], [tenecteplase] and [reteplase], have also been developed.[A252270,A252345] Alteplase is also available as Cathflo Activase (intracatheter instillation) for the restoration of function to central venous access devices.[L34864]

liquid

Alteplase is indicated for the treatment of acute ischemic stroke (AIS) and for use in acute myocardial infarction (AMI) for the reduction of mortality and incidence of heart failure. Alteplase is also indicated for the lysis of acute massive pulmonary embolism, defined as acute pulmonary emboli obstructing blood flow to a lobe or multiple lung segments, and acute pulmonary emboli accompanied by unstable hemodynamics.[L43125]

Alteplase binds to fibrin and plasminogen. Alteplase specificity for fibrin is achieved thanks to its high affinity for lysine residues. Also, it can bind plasminogen via loop structures called kringles, stabilized by three disulphide linkages similar to the ones in plasminogen. The specificity of alteplase for plasminogen bound to fibrin allows this drug to act in a clot- or fibrin-specific manner, leading to low concentrations of circulating plasmin and a lower risk of hemorrhagic transformation.[A252270,A252330] In patients with acute myocardial infarction, alteplase reduces fibrinogen levels 3 to 6 hours after treatment. In patients with acute ischemic stroke, patients treated with alteplase have a significantly higher resolution of hyperdense artery sign, a marker of clot formation in the proximal middle cerebral artery, compared to those treated with placebo.[A252330] The use of alteplase increases the risk of bleeding and thromboembolic events. Rare cases of cholesterol embolism have also been reported.[L43125]

Alteplase is a recombinant tissue plasminogen activator (rt-PA) that converts plasminogen to plasmin in a fibrin-dependent process. In the absence of fibrin, alteplase converts a limited amount of plasminogen. However, in the presence of fibrin clots, alteplase binds to fibrin and cleaves the arginine-valine bond at positions 560 and 561 of plasminogen, converting it into its active form, plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus and promotes clot dissolution.[A252270] Alteplase initiates local fibrinolysis with limited systemic proteolysis.[L43125]

Healthy volunteers with a baseline endogenous tissue plasminogen activator (t-PA) of 3.3 ng/ml had a 290-fold increase in baseline concentrations after receiving alteplase at an infusion rate of 0.25 mg/kg for 30 min; with an infusion rate of 0.5 mg/kg, a 550-fold increase was observed.[A252270] Acute myocardial infarction patients (n=12) given 10 mg of alteplase in a 2-minute infusion reached a peak plasma concentration of 3310 ng/ml. This was followed by 50 mg of alteplase in 1 h and 30 mg in 1.5 h, resulting in steady-state plasma levels of 2210 ng/ml and 930 ng/ml, respectively.[A252285]

Alteplase is mainly metabolized by the liver. The carbohydrate and polypeptide domains of alteplase interact with hepatic glycoprotein receptors, leading to receptor-mediated endocytosis.[A252270] _In vivo_ studies suggest that alteplase follows zero-order kinetics, meaning that its metabolism is saturable at higher plasma concentrations.[A252270]

Toxicity information regarding alteplase is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as risk of bleeding and thromboembolic events.[L43125] Symptomatic and supportive measures are recommended. The carcinogenic potential of alteplase or its effect on fertility have not been evaluated. _In vivo_ studies evaluating tumorigenicity and _in vitro_ studies evaluating mutagenicity were negative.[L43125] It has been estimated that the acute oral and dermal toxicity of alteplase is above 5,000 mg/kg.[L43175]

Alteplase has an initial half-life of less than 5 minutes in patients with acute myocardial infarction (AMI). The dominant initial plasma half-life of the 3-hour and the accelerated regimens for AMI are similar.[L43125]

Not available.

In healthy volunteers, more than 80% of alteplase is eliminated through urine 18 hours after administration.[A252270]

The initial volume of distribution approximates plasma volume.[L43125] The average volume of distribution of the central compartment goes from 3.9 to 4.3 L, and the volume of distribution at steady state goes from 7.2 to 12 L.[A252270]

Alteplase has a plasma clearance between 380 and 570 mL/min.[L43125]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "B01AD", "B01A", "B01", "B", "S01XA", "S01X", "S01", "S" ]

[ "Humans and other mammals" ]

[ { "cost": "106.33", "description": "Cathflo activase 2 mg vial", "unit": "vial" }, { "cost": "2389.85", "description": "Activase 50 mg vial", "unit": "vial" }, { "cost": "4779.71", "description": "Activase 100 mg vial", "unit": "vial" } ]

[]

[ "Activase", "Activase", "Activase RT-PA", "Activase RT-PA", "Activase RT-PA Inj", "Activase RT-PA Inj", "Activase RT-PA Inj", "Cathflo", "Cathflo Activase", "Lysatec RT - Pa" ]

[]

[ "Lysatec RT - Pa", "Activase RT-PA", "Activase RT-PA" ]

[ "P00747", "P02671", "P02679", "P05121" ]

[]

DB00010

Sermorelin

Sermorelin acetate is the acetate salt of an amidated synthetic 29-amino acid peptide (GRF 1-29 NH 2 ) that corresponds to the amino-terminal segment of the naturally occurring human growth hormone-releasing hormone (GHRH or GRF) consisting of 44 amino acid residues

liquid

For the treatment of dwarfism, prevention of HIV-induced weight loss

Sermorelin is used in the treatment of children with growth hormone deficiency or growth failure. Geref increases plasma growth hormone (GH) concentration by stimulating the pituitary gland to release GH. Geref is similar to the full-length native hormone (44 residues) in its ability to stimulate GH secretion in humans.

Sermorelin binds to the growth hormone releasing hormone receptor and mimics native GRF in its ability to stimulate growth hormone secretion.

null

11-12 min

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "withdrawn" ]

[ "V04CD", "V04C", "V04", "V", "H01AC", "H01A", "H01", "H" ]

[ "Humans and other mammals" ]

[]

Sermorelin | GHRH receptor | GRF receptor | GRFR | Growth hormone-releasing factor receptor

[]

[ "Geref" ]

[]

[ "Q02643" ]

[]

DB00011

Interferon alfa-n1

Interferon alfa-n1 consists of purified, natural (n is for natural) alpha interferon subtypes, at least two of which are glycosylated. This differs from recombinant alpha interferons, which are individual non-glycosylated proteins produced from individual alpha interferon genes.

liquid

For the treatment of venereal or genital warts caused by the Human Papiloma Virus.

Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R.

Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta.

null

1.2 hours (mammalian reticulocytes, in vitro); >20 hours (yeast, in vivo); >10 hours (Escherichia coli, in vivo).

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L03AB", "L03A", "L03", "L" ]

[ "Humans and other mammals" ]

[]

[ "Wellferon Inj 10 000 000unit/ml", "Wellferon Inj 3000000unit/ml" ]

[ "Wellferon" ]

[]

[ "P17181", "P48551" ]

[ "P05177" ]

[]

DB00012

Darbepoetin alfa

Human erythropoietin with 2 aa substitutions to enhance glycosylation (5 N-linked chains), 165 residues (MW=37 kD). Produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology.

liquid

For the treatment of anemia (from renal transplants or certain HIV treatment)

Darbepoetin alfa is used in the treatment of anemia. It is involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass.

Darbepoetin alfa stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. Erythropoietin interacts with progenitor stem cells to increase red cell production. Binding of erythropoietin to the erythropoietin receptor leads to receptor dimerization, which facilitates activation of JAK-STAT signaling pathways within the cytosol. Activated STAT (signal transducers and activators of transcription) proteins are then translocated to the nucleus where they serve as transcription factors which regulate the activation of specific genes involved in cell division or differentiation.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "B03XA", "B03X", "B03", "B" ]

[ "Humans and other mammals" ]

[ { "cost": "156.36", "description": "Aranesp 25 mcg/ml vial", "unit": "ml" }, { "cost": "162.61", "description": "Aranesp (Albumin Free) 25 mcg/ml vial", "unit": "vial" }, { "cost": "250.2", "description": "Aranesp 40 mcg/ml vial", "unit": "ml" }, { "cost": "375.3", "description": "Aranesp 60 mcg/ml vial", "unit": "ml" }, { "cost": "390.31", "description": "Aranesp (Albumin Free) 60 mcg/ml vial", "unit": "vial" }, { "cost": "625.44", "description": "Aranesp 100 mcg/ml vial", "unit": "ml" }, { "cost": "1250.88", "description": "Aranesp 200 mcg/ml vial", "unit": "ml" }, { "cost": "1876.32", "description": "Aranesp 300 mcg/ml vial", "unit": "ml" }, { "cost": "1951.37", "description": "Aranesp (Albumin Free) 300 mcg/ml vial", "unit": "vial" }, { "cost": "2601.83", "description": "Aranesp (Albumin Free) 100 mcg/0.5ml Solution (1 Box = Four 0.5ml Syringes)", "unit": "box" }, { "cost": "2601.83", "description": "Aranesp (Albumin Free) 100 mcg/ml Solution Four 1ml Vials Per Box", "unit": "box" }, { "cost": "3902.75", "description": "Aranesp (Albumin Free) 150 mcg/0.75ml Solution (1 Box = Four 0.75ml Vials)", "unit": "box" } ]

[ { "approved": "2003-03-18", "country": "Canada", "expires": "2010-10-15", "number": "2165694" }, { "approved": "2002-11-05", "country": "Canada", "expires": "2014-08-16", "number": "2147124" } ]

Darbepoetin | Darbepoetin alfa | Darbepoetin alfa,recombinant | Darbepoetina alfa | EPO-R

[ "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp", "Aranesp -(hsa-free)", "Aranesp -(hsa-free)", "Aranesp -(hsa-free)", "Aranesp -(hsa-free)", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo", "Nespo" ]

[]

[ "P19235" ]

[]

DB00013

Urokinase

Urokinase is an endogenous peptide that is cleaved in the presence of plasmin between lysine 158 and isoleucine 159 to yield active urokinase.[A191943] Urokinase remains connected between these 2 chains by a sulfhydryl bond.[A191943] Urokinase was granted FDA approval on 16 January 1978.[L12138]

liquid

In Canada, urokinase is indicated for lysis of acute massive pulmonary emboli, acute thrombi obstructing coronary arteries, occlusive thromboemboli in peripheral arteries and grafts, and restoration of patency to intravenous catheters.[L12141]

Urokinase is a serine protease that activates plasminogen to an active fibrinolytic protease.[A191928] The duration of action is short due to the short half life.[L12138] Patients should be counselled regarding the risk of bleeding, anaphylaxis, infusion reactions, and cholesterol embolization.[L12138

Urokinase is a serine protease.[A191928] It cleaves plasminogen to form the active fibrinolytic protease, plasmin.[A191928]

Urokinase is delivered intravenously, so the bioavailability is high.

Because urokinase is a protein, it is expected to be metabolized by proteases to smaller proteins and amino acids.

Patients experiencing an overdose may present with bleeding.[L12141] Treat patients with symptomatic and supportive measures which may include application of local pressure, administration of whole blood or plasma, and administration of aminocaproic acid.[L12141]

Urokinase has a half life of 12.6±6.2 minutes.[L12138]

Data regarding the protein binding of urokinase in plasma is not readily available.

Urokinase is eliminated in the bile and urine.[L12138]

The volume of distribution of urokinase is 11.5L.[L12138]

Data regarding the clearance of urokinase is not readily available.

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational", "withdrawn" ]

[ "B01AD", "B01A", "B01", "B" ]

[ "Humans and other mammals" ]

[]

[ "Kinlytic", "Kinlytic (urokinase for Injection)", "Kinlytic Open-cath" ]

[ "Abbokinase" ]

[]

[ "P00747", "Q03405", "P05121", "P05120", "P05154", "P98164", "Q9Y5Y6", "P14543" ]

[ "P39900" ]

[]

DB00014

Goserelin

Goserelin is a synthetic hormone. In men, it stops the production of the hormone testosterone, which may stimulate the growth of cancer cells. In women, goserelin decreases the production of the hormone estradiol (which may stimulate the growth of cancer cells) to levels similar to a postmenopausal state. When the medication is stopped, hormone levels return to normal.

solid

Goserelin is indicated for: - Use in combination with flutamide for the management of locally confined carcinoma of the prostate - Palliative treatment of advanced carcinoma of the prostate - The management of endometriosis - Use as an endometrial-thinning agent prior to endometrial ablation for dysfunctional uterine bleeding - Use in the palliative treatment of advanced breast cancer in pre- and perimenopausal women

The pharmacokinetics of goserelin have been determined in both male and female healthy volunteers and patients. In these studies, goserelin was administered as a single 250µg (aqueous solution) dose and as a single or multiple 3.6 mg depot dose by subcutaneous route.

Goserelin is a synthetic decapeptide analogue of LHRH. Goserelin acts as a potent inhibitor of pituitary gonadotropin secretion when administered in the biodegradable formulation. The result is sustained suppression of LH and serum testosterone levels.

Inactive orally, rapidly absorbed following subcutaneous administration.

Hepatic

No experience of overdosage from clinical trials.

4-5 hours

27.3%

Clearance of goserelin following subcutaneous administration of a radiolabeled solution of goserelin was very rapid and occurred via a combination of hepatic and urinary excretion. More than 90% of a subcutaneous radiolabeled solution formulation dose of goserelin was excreted in urine.

* 44.1 ± 13.6 L [subcutaneous administration of 250 mcg]

* 121 +/- 42.4 mL/min [prostate cancer with 10.8 mg depot]

Organic compounds

Organic acids and derivatives

Carboxylic acids and derivatives

Amino acids, peptides, and analogues

[ "approved" ]

[ "L02AE", "L02A", "L02", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "451.19", "description": "Zoladex 3.6 mg implant syringe", "unit": "syringe" }, { "cost": "1380.65", "description": "Zoladex 10.8 mg implant syringe", "unit": "syringe" } ]

[ { "approved": "2006-10-10", "country": "United States", "expires": "2022-04-13", "number": "7118552" }, { "approved": "2007-05-22", "country": "United States", "expires": "2022-04-09", "number": "7220247" }, { "approved": "2009-03-10", "country": "United States", "expires": "2021-02-26", "number": "7500964" } ]

[ "Zoladex", "Zoladex", "Zoladex", "Zoladex", "Zoladex", "Zoladex", "Zoladex", "Zoladex LA" ]

[]

[ "P22888", "P01148", "P30968" ]

[]

DB00015

Reteplase

Human tissue plasminogen activator, purified, glycosylated, 355 residues purified from CHO cells. Retavase is considered a "third-generation" thrombolytic agent, genetically engineered to retain and delete certain portions of human tPA. Retavase is a deletion mutein of human tPA formed by deleting various amino acids present in endogenous human tPA. Retavase contains 355 of the 527 amino acids of native human tPA (amino acids 1-3 and 176-527), and retains the activity-related kringle-2 and serine protease domains of human tPA. Three domains are deleted from retavase - kringle-1, finger, and epidermal growth factor (EGF).

liquid

For lysis of acute pulmonary emboli, intracoronary emboli, and management of myocardial infarction.

Reteplase cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action. This helps eliminate blood clots or arterial blockages that cause myocardial infarction.

Reteplase binds to fibrin rich clots via the fibronectin finger-like domain and the Kringle 2 domain. The protease domain then cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "B01AD", "B01A", "B01", "B" ]

[ "Humans and other mammals" ]

[ { "cost": "2605.93", "description": "Retavase vial half-kit", "unit": "vial" } ]

[ { "approved": "2007-12-18", "country": "Canada", "expires": "2012-04-15", "number": "2107476" } ]

[ "Rapilysin", "Retavase", "Retavase", "Retavase", "Retavase", "Retavase" ]

[]

[ "P00747", "P02671", "P05121" ]

[]

DB00016

Erythropoietin

Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously.

liquid

Indicated in adult and paediatric patients for the: - treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis. - treatment of anemia due to zidovudine in patients with HIV-infection. - treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy. - reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery.

Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label].

Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ∼100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C-γ1 [A33079].

The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration).[A33080] The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40%.[A33080] **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label].

Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080].

Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label].

**Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]. **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label].

No information of serum protein binding available.

Erythropoietin and epoetin alfa are cleared via uptake and degradation via the EPO-R-expressing cells, and may also involve other cellular pathways in the interstitium, probably via cells in the reticuloendothelial scavenging pathway or lymphatic system [A33080]. Only a small amount of unchanged epoetin alfa is found in the urine [F86].

In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076].

**Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label].

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "B03XA", "B03X", "B03", "B" ]

[ "Humans and other mammals" ]

[ { "cost": "34.14", "description": "Epogen 2000 unit/ml vial", "unit": "vial" }, { "cost": "37.09", "description": "Procrit 2000 unit/ml vial", "unit": "vial" }, { "cost": "47.53", "description": "Epogen 3000 unit/ml vial", "unit": "vial" }, { "cost": "55.63", "description": "Procrit 3000 unit/ml vial", "unit": "vial" }, { "cost": "61.34", "description": "Epogen 4000 unit/ml vial", "unit": "vial" }, { "cost": "74.17", "description": "Procrit 4000 unit/ml vial", "unit": "vial" }, { "cost": "151.8", "description": "Epogen 10000 unit/ml vial", "unit": "ml" }, { "cost": "303.6", "description": "Epogen 20000 unit/ml vial", "unit": "ml" }, { "cost": "315.74", "description": "Epogen 10000 unit/ml Solution 2ml Vial", "unit": "vial" }, { "cost": "358.02", "description": "Procrit 10000 unit/ml Solution 2ml Vial", "unit": "vial" }, { "cost": "378.14", "description": "Procrit 20000 unit/ml Solution", "unit": "ml" }, { "cost": "388.97", "description": "Procrit 20000 unit/ml vial", "unit": "ml" }, { "cost": "640.37", "description": "Epogen 40000 unit/ml vial", "unit": "ml" }, { "cost": "710.87", "description": "Procrit 10000 unit/ml vial", "unit": "vial" }, { "cost": "767.03", "description": "Procrit 40000 unit/ml vial", "unit": "vial" }, { "cost": "1578.72", "description": "Epogen 10000 unit/ml Solution 1 Box Contains Ten 1ml Vials", "unit": "box" }, { "cost": "3157.44", "description": "Epogen 20000 unit/ml Solution 1 Box Contains Ten 1ml Vials", "unit": "box" }, { "cost": "6852.3", "description": "Epogen 40000 unit/ml Solution 1 Box Contains Ten 1ml Vials", "unit": "box" } ]

[ { "approved": "1997-05-27", "country": "Canada", "expires": "2014-05-27", "number": "1339047" } ]

[ "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Abseamed", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", "Binocrit", 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Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epoetin Alfa Hexal", "Epogen", "Epogen", "Epogen", "Epogen", "Epogen", "Epogen", "Epogen", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eporatio", "Eprex Sterile Solution", "Eprex Sterile Solution", "Eprex Sterile Solution 10000iu/1.0ml", "Eprex Sterile Solution 10000iu/ml", "Eprex Sterile Solution 1000iu/0.5ml", "Eprex Sterile Solution 20000iu/ml", "Eprex Sterile Solution 2000iu/0.5ml", "Eprex Sterile Solution 2000iu/ml", "Eprex Sterile Solution 3000iu/0.3ml", "Eprex Sterile Solution 40000iu/ml", "Eprex Sterile Solution 4000iu/0.4ml", "Eprex Sterile Solution 4000iu/ml", "Eprex Sterile Solution 5000iu/0.5ml", "Eprex Sterile Solution 6000 Iu/0.6 Ml", "Eprex Sterile Solution 8000 Iu/0.8 Ml", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon", "Neorecormon Guard", "Neorecormon Guard", "Procrit", "Procrit", "Procrit", "Procrit", "Procrit", "Procrit", "Procrit", "Procrit", "Procrit", "Procrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Retacrit", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo", "Silapo" ]

[ "Epobel", "Epocept", "Epofit", "Epogin", "Eqralys", "Nanokine" ]

[]

[ "P19235" ]

[]

DB00017

Salmon calcitonin

Synthetic peptide, 32 residues long formulated as a nasal spray.

liquid

Used in the treatment of symptomatic Paget's disease for patients unresponsive to alternate treatments or intolerant to such treatments. In addition, it is used in emergency situations when serum calcium levels must be decreased quickly until the underlying condition is identified. It can also be added to existing therapeutic regimens for hypercalcemia such as intravenous fluids and furosemide, oral phosphate or corticosteroids, or other agents. Calcitonin can be used in patients with azotemia and cases where intravenous fluids would be contraindicated due to limited cardiac reserves. Also for the treatment of post-menopausal osteoporosis in women more than 5 years post-menopause.

Calcitonin inhibits bone resorption by osteoclasts (bone remodeling cells) and promotes bone formation by osteoblasts. This leads to a net increase in bone mass and a reduction in plasma calcium levels. It also promotes the renal excretion of ions such as calcium, phosphate, sodium, magnesium, and potassium by decreasing tubular reabsorption. In consequence, there is an increase in the jejunal secretion of water, sodium, potassium, and chloride.

Calcitonin binds to the calcitonin receptor (found primarily in osteoclasts) which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway.

Salmon calcitonin is rapidly absorbed with bioavailability of 71% following subcutaneous injection and 66% following intramuscular injection in humans. Via the nasal route, the bioavailability varies between 3 to 5% relative to IM.

Salmon calcitonin primarily undergoes degradation in the kidneys to form pharmacologically inactive metabolites. It is also metabolized in the blood and the peripheral tissue.

Salmon calcitonin was shown to inhibit lactation in animals and is not recommend in nursing mothers. While research in animals have shown a decrease in fetal weight, no studies have yet shown similar results in humans. It is recommended however to proceed carefully when administering salmon calcitonin to pregnant women and consider if the benefits outweigh the risks. Because of its protein nature, salmon calcitonin may provoke an allergy reaction (bronchospams and swelling of the tongue/throat) that can turn into a full-blown anaphylactic response. The manufacturer also reports an increase in the risk of malignancies from oral route (0.7%) to intranasal route (2.4%) compared to placebo. The same may apply to IV, IM and SC routes since the systemic exposure is higher in those cases. Nausea is noticeable in some patients but tends to decrease with continued administration. Rhinitis, headaches and back pain have also been reported among others.

Half-life elimination (terminal): I.M. 58 minutes; SubQ 59 to 64 minutes; Nasal: ~18 to 23 minutes

Protein binding is about 30 to 40%.

Urine. Studies with injectable calcitonin show increases in the excretion of filtered phosphate, calcium, and sodium by decreasing their tubular reabsorption in the kidney.

0.15 to 0.3 L/kg

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "H05BA", "H05B", "H05", "H" ]

[ "Humans and other mammals" ]

[ { "cost": "8.81", "description": "Caltine 100 (100 Iu/Ml) 100 iu/ml", "unit": "ml" }, { "cost": "29.94", "description": "Calcimar 200 iu/ml", "unit": "ml" }, { "cost": "30.73", "description": "Miacalcin 200 unit/ml vial", "unit": "ml" }, { "cost": "34.3", "description": "Fortical 200 unit nasal spray", "unit": "ml" }, { "cost": "39.51", "description": "Calcitonin-salmon 200 unit sp", "unit": "ml" }, { "cost": "44.68", "description": "Miacalcin 200 unit nasal spray", "unit": "ml" }, { "cost": "63.59", "description": "Miacalcin For Inj, 2 unit = 1 Box 2ml Vial", "unit": "vial" }, { "cost": "123.28", "description": "Calcitonin (Salmon) 200 unit/act Solution 3.7ml Bottle", "unit": "bottle" }, { "cost": "139.39", "description": "Miacalcin 200 unit/act Solution 3.7ml Bottle", "unit": "bottle" } ]

[ { "approved": "1998-03-31", "country": "United States", "expires": "2015-03-31", "number": "5733569" }, { "approved": "2002-08-27", "country": "United States", "expires": "2021-02-02", "number": "6440392" }, { "approved": "2012-08-14", "country": "United States", "expires": "2021-02-02", "number": "RE43580" }, { "approved": "2009-06-30", "country": "United States", "expires": "2021-02-02", "number": "RE40812" } ]

[ "Apo-calcitonin Injectable", "Apo-calcitonin Nasal Spray", "Calcimar", "Calcitonin Salmon", "Calcitonin Salmon", "Calcitonin Salmon", "Calcitonin Salmon", "Calcitonin Salmon", "Calcitonin Salmon", "Calcitonin Salmon", "Calcitonin Salmon", "Calcitonin Salmon", "Calcitonin Salmon", "Calcitonin Salmon", "Calcitonin Salmon", "Calcitonin Salmon Injection USP", "Caltine Inj 100 Unit/ml (1ml Amp)", "Caltine Inj 100unit/ml (0.5ml Amp)", "Forcaltonin", "Fortical", "Fortical", "Miacalcin", "Miacalcin", "Miacalcin", "Miacalcin", "Miacalcin", "Miacalcin", "Miacalcin", "Miacalcin Injection 200iu/ml", "Miacalcin Nasal Spray 200 Iu", "Pro-calcitonin - 200", "Sandoz-calcitonin NS" ]

[ "Calcimar" ]

[]

[ "P30988" ]

[]

DB00018

Interferon alfa-n3

Purified, natural (n is for natural) human interferon alpha proteins (consists of 3 forms or polymorphisms including 2a, 2b and 2c). 166 residues, some are glycosylated (MW range from 16 kD to 27 kD).

liquid

For the intralesional treatment of refractory or recurring external condylomata acuminata.

Interferon alfa-n3 upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase), beta-2 microglobulin, neopterin and protein kinase R.

Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription) which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[]

[ "Humans and other mammals" ]

[ { "cost": "412.87", "description": "Alferon n 5 million unit vial", "unit": "ml" } ]

[]

[ "Alferon" ]

[ "Alferon", "Alferon N" ]

[]

[ "P17181", "P48551" ]

[ "P05177" ]

[]

DB00019

Pegfilgrastim

Pegfilgrastim is a PEGylated form of the recombinant human granulocyte colony-stimulating factor (G-CSF) analogue, [filgrastim].[A187601] The drug is approved for use to decrease the incidence of infection, as manifested by febrile neutropenia, in susceptible patients with with non-myeloid cancer receiving myelosuppressive anti-cancer treatment.[L9746] Although the risk of developing febrile neutropenia is less than 20% in many readily used chemotherapy regimens,[A248855] infections pose risks of hospitalization and mortalities.[A187631] Due to the relatively short circulating half-life of filgrastim, a 20 kDa PEG moiety was covalently conjugated to the N-terminus of filgrastim (at the methionine residue) to develop longer-acting pegfilgrastim.[A29,A187607] Due to a longer half-life and slower elimination rate than filgrastim, pegfilgrastim requires less frequent dosing than filgrastim; however, pegfilgrastim has a comparable pharmacological activity to filgrastim and binds to the G-CSF receptor to stimulate the proliferation, differentiation, and activation of neutrophils.[A187607] First developed by Amgen, pegfilgrastim was initially approved by the FDA in 2002 and marketed as Neulasta. It is typically administered via a subcutaneous injection. There are several pegfilgrastim biosimilars (Fulphila, Pelgraz or Lapelga, Pelmeg, Udenyca, Ziextenzo, Grasustek, Fylnetra, Stimufend) by Health Canada, European Union (EU), and FDA that are approved to reduce infection risk.[L9779,L9785,L43050] These biosimilars are highly similar to the reference product, Neulasta, in terms of pharmacological and pharmacokinetic profile and conditions of use.[L9974]

liquid

Pegfilgrastim is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.[L44221] It is also indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome).[L44221]

Pegfilgrastim is a recombinant human granulocyte colony-stimulating factor (G-CSF) that promotes the production, proliferation, and maturation of neutrophils, which are white blood cells involved in both innate and adaptive immune responses.[A187631,A248855] The safety and efficacy of pegfilgrastim in reducing the risk of febrile neutropenia and infections have been demonstrated in various tumor types and settings.[A187631] During chemotherapy-induced neutropenia, the clearance of pegfilgrastim is significantly reduced and the concentration of pegfilgrastim is sustained until the onset of neutrophil recovery.[A29] Serum concentrations of pegfilgrastim decline as the neutrophil count increases as neutrophil and neutrophil precursors are involved in cell-mediated clearance of the drug.[A187601] Due the addition of polyethylene glycol group to its structure, Pegfilgrastim is a long-acting form of filgrastim with an extended serum half-life and reduced renal clearance.[A187607] Although it is more slowly absorbed than filgrastim, self-regulation of pegfilgrastim is more efficient and the drug effects are maintained during one chemotherapy cycle (2-3 weeks).[A29]

Neutrophils are short-lived immune cells that are highly susceptible to cell death following myelosuppressive chemotherapy. This marked reduction in neutrophil numbers during chemotherapy increases the risk of hospitalization, infection, and infection-related mortality. It also directly impacts the clinical outcome of patients if cases of febrile neutropenia requires dose reductions or schedule delay of chemotherapy, thus reducing the clinical efficacy of chemotherapy and patient benefit from receiving appropriate treatment.[A187631] G-CSF is an endogenous haematopoietic growth factor that stimulates granulopoietic cells of the neutrophil lineage. Pegfilgrastim mimics its biological actions and binds to the same G-CSF receptor expressed on cells of myeloid lineage, such as granulocytic precursors and mature neutrophils.[A29] Upon binding of the ligand, G-CSF receptor undergoes a conformational change and activates several downstream signalling pathways including JAK/STAT, PI3K/AKT and MAPK/ERK.[A187868] These pathways work to increase proliferation and differentiation of granulocyte progenitor cells, induce maturation of the progenitor cells, and enhance survival and function of mature neutrophils.[A29]

Pegfilgrastim has a lower absolute bioavailability than filgrastim following subcutaneous administration. The absorption of pegfilgrastim is largely dependent on the lymphatic system due to the attached PEG group contributing to the large size of the drug. It is slowly absorbed following subcutaneous administration with a time to peak concentration (Tmax) of about one to two days.[A29]

It is not know whether pegfilgrastim is metabolized into major metabolites.[L10022] Once it binds to the therapeutic target, pegfilgrastim is internalized by the neutrophil and undergoes nonspecific degradation.[A29]

The maximum safe dose of pegfilgrastim has not been established; however, the highest dose used in clinical trials was 300 mcg/kg.[A248855] Overdosage of pegfilgrastim may result in leukocytosis and bone pain. Events of edema, dyspnea, and pleural effusion have been reported in a single patient who self-administered pegfilgrastim on 8 consecutive days in error. In the event of overdose, the patient should be monitored for signs and symptoms of toxicity and responded with appropriate general supportive care.[L9746,A248855]

The serum half-life of Pegfilgrastim is highly variable depending on the absolute neutrophil count, with the range of 15 to 80 hours following subcutaneous administration. The median serum half-life of 42 hours.[A187607,L9746]

The plasma protein binding of pegfilgrastim is unlikely.[L10022]

The polyethylene glycol moiety limits the renal clearance by glomerular filtration of pegfilgrastim, making neutrophil-mediated clearance as the predominant route of elimination.[A187607] This elimination pathway is initiated by the binding of pegfilgrastim to the G-CSF receptor on the neutrophil cell surface, leading to the internalization of the pegfilgrastim-receptor complex via endocytosis and subsequent degradation inside the cell. While hepatic clearance has not been well characterized for pegfilgrastim, its non-PEGylated precursor filgrastim is known to be unaffected by changes in hepatic clearance.[A29]

Pegfilgrastim appears to have a volume of distribution of approximately 170 L.[A33290]

Pegfilgrastim has a self-regulating clearance that involves neutrophil-induced clearance.[A29,A187631] The clearance is dependent on the number of neutrophils and body weight of the patient: the clearance increases with increasing number of granulocytes and lower body weights.[L9746] Pegfilgrastim is not eliminated from the circulation until neutrophils start to recover following chemotherapy-induced neutropenia and its clearance is increased as neutrophil counts also increase.[A187631] The apparent serum clearance is 14 mL/h/kg.[L10022]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "L03AA", "L03A", "L03", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "4026.05", "description": "Neulasta 6 mg/0.6ml Solution 0.6ml Syringe", "unit": "syringe" }, { "cost": "4102.37", "description": "Neulasta 6 mg/0.6 ml syringe", "unit": "syringe" } ]

[ { "approved": "2007-07-31", "country": "Canada", "expires": "2024-07-31", "number": "1341537" }, { "approved": "1997-07-29", "country": "Canada", "expires": "2014-07-29", "number": "1339071" } ]

[ "Armlupeg", "Cegfila", "Fulphila", "Fulphila", "Fulphila", "Fulphila", "Fulphila", "Fylnetra", "Grasustek", "Lapelga", "Lapelga", "Neulasta", "Neulasta", "Neulasta", "Neulasta", "Neulasta", "Neulasta", "Neulasta", "Neulasta", "Neupopeg", "Neupopeg", "Neupopeg", "Niopeg", "Nyvepria", "Nyvepria", "Nyvepria", "Pelgraz", "Pelgraz", "Pelmeg", "Ristempa", "Ristempa", "Ristempa", "Stimufend", "Stimufend", "Udenyca", "Udenyca", "Udenyca", "Udenyca", "Ziextenzo", "Ziextenzo", "Ziextenzo" ]

[]

[ "Q99062" ]

[ "P08246" ]

[]

DB00020

Sargramostim

Sargramostim is a human recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) expressed in yeast. It is a glycoprotein that is 127 residues. Substitution of Leu23 leads to a difference from native protein.

liquid

For the treatment of cancer and bone marrow transplant

Sargramostim is used in the treatment of bone marrow transplant recipients or those exposed to chemotherapy an recovering from acut myelogenous leukemia, Leukine or GM-CSF is a hematopoietic growth factor which stimulates the survival, clonal expansion (proliferation) and differentiation of hematopoietic progenitor cells. GM-CSF is also capable of activating mature granulocytes and macrophages. After a bone marrow transplant or chemotherapy, patients have a reduced capacity to produce red and white blood cells. Supplementing them with external sources of GM-CSF helps bring the level of neutrophils back to normal so that they can better fight infections.

Sargramostim binds to the Granulocyte-macrophage colony stimulating factor receptor (GM-CSF-R-alpha or CSF2R) which stimulates a JAK2 STAT1/STAT3 signal transduction pathway. This leads to the production of hemopoietic cells and neutrophils

null

* 420 mL/min/m2 [Normal people with liquid LEUKINE (IV)] * 431 mL/min/m2 [Normal people with lyophilized LEUKINE (IV)] * 549 mL/min/m2 [Normal people with liquid LEUKINE (SC)] * 529 mL/min/m2 [Normal people with lyophilized LEUKINE (SC)]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L03AA", "L03A", "L03", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "204.79", "description": "Leukine 250 mcg vial", "unit": "vial" }, { "cost": "0.42", "description": "Bio-immunex capsule", "unit": "capsule" } ]

[ { "approved": "2000-12-05", "country": "Canada", "expires": "2017-12-05", "number": "1341150" } ]

[ "Leukine", "Leukine", "Leukine", "Leukine", "Leukine", "Leukine", "Leukine", "Leukine", "Leukine", "Leukine" ]

[ "Leucomax" ]

[]

[ "P15509", "P26951", "P32927", "P34741", "P13727" ]

[]

DB00022

Peginterferon alfa-2b

Peginterferon alfa-2b is a form of recombinant interferon used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [L852]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) resulting in less use of Peginterferon alfa-2b. Peginterferon alfa-2b is derived from the alfa-2b moeity of recombinant human interferon and acts by binding to human type 1 interferon receptors. Activation and dimerization of this receptor induces the body's innate antiviral response by activating the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Use of Peginterferon alfa-2b is associated with a wide range of severe adverse effects including the aggravation and development of endocrine and autoimmune disorders, retinopathies, cardiovascular and neuropsychiatric complications, and increased risk of hepatic decompensation in patients with cirrhosis. The use of Peginterferon alfa-2b has largely declined since newer interferon-free antiviral therapies have been developed. In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) no longer recommend Peginterferon alfa-2b for the treatment of Hepatitis C [A19593]. Peginterferon alfa-2b was used alongside [DB00811] with the intent to cure, or achieve a sustained virologic response (SVR), after 48 weeks of therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality [A19626]. Peginterferon alfa-2b is available as a variable dose injectable product (tradename Pegintron) used for the treatment of chronic Hepatitis C. Approved in 2001 by the FDA, Pegintron is indicated for the treatment of HCV with [Ribavirin] or other antiviral drugs [FDA Label]. When combined together, Peginterferon alfa-2b and [Ribavirin] have been shown to achieve a SVR between 41% for genotype 1 and 75% for genotypes 2-6 after 48 weeks of treatment.

liquid

Peginterferon alfa-2b is indicated for the treatment of HCV in combination with [DB00811] and a NS3/4A protease inhibitor for genotype 1 or without a NS3/4A protease inhibitor for genotypes 2-6 [FDA Label]. May be used as a monotherapy in patients with contraindications to or significant intolerance to other anti-viral therapies. It is also indicated for the adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection, including complete lymphadenectomy.[L45334]

Peginterferon alfa-2b inhibits viral replication in infected cells, suppresses cell proliferation, induces apoptosis, and exerts an anti-angiogenic effect [FDA Label]. Exerts immunomodulatory effects such as enhancement of the phagocytic activity of macrophages, activation of NK cells, stimulation of cytotoxic T-lymphocytes, and the upregulation of the Th1 T-helper cell subset. Also increases concentrations of effector proteins such as serum neopterin and 2'5' oligoadenylate synthetase, raises body temperature, and causes reversible decreases in leukocyte and platelet counts.

Peginterferon alfa-2b is derived from recombinant human interferon's alfa-2b moeity [FDA Label]. It binds to and activates human type 1 interferon receptors causing them to dimerize. This activates the JAK/STAT pathway. Activation of the JAK/STAT pathway increases expression of multiple genes in multiple tissues involved in the innate antiviral response. Peginterferon alfa-2b may also acitvate the nuclear factor κB pathway.

Peginterferon alfa-2b reaches peak plasma concentration 15-44 hours after subcutaneous administration [FDA Label]. The mean absorption half-life is 4.6 hours. After multiple doses the bioavailability of Peginterferon alfa-2b increases with trough concentrations at week 48 3-fold higher than those at week 4.

null

Peginterferon alfa-2b may manifest neuropsychiatric complications include suicide, suicidal ideation, homicidal ideation, depression, relapse of drug addiction, and drug overdose [FDA Label]. Hypertension, supraventricular arrhythmias, chest pain, and myocardial infarction have been observed in patients using Peginterferon alfa-2b. Peginterferon alfa-2b may produce myelosuppression as well as the development or aggravation of autoimmune disorders including myositis, hepatitis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus. Peginterferon alfa-2b causes or aggravates hypothyroidism and hyperthyroidism. Hyperglycemia, hypoglycemia, and diabetes mellitus have been observed to develop in patients treated with Peginterferon alfa-2b. Peginterferon alfa-2b may decrease or produce loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, papilledema and serous retinal detachment. Peginterferon mayy be related to increased ischemic and hemorrhagic cerebrovascular events. Patients with cirrhosis on Peginterferon alfa-2b are at risk of hepatic decompensation. Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension and sarcoidosis may be induced or aggravated by Peginterferon alfa-2b. Serious and severe infections (bacterial, viral, or fungal) have been reported during treatment with Peginterferon alfa-2b. Ulcerative and hemorrhagic/ischemic colitis have been observed within 12 weeks of starting Peginterferon alfa-2b treatment. Pancreatitis and peripheral nephropathy have also been reported. Peginterferon alfa-2b is associated with growth inhibition in pediatric patients. Use of Peginterferon alfa-2b while pregant may result in delopmental abnormalities or death of the fetus.

The mean half-life of elimination of Peginterferon alfa-2b is 40 hours in a range of 22-60 hours [FDA Label].

null

Renal elimination accounts for 30% of Peginterferon alfa-2b elimination [FDA Label].

null

The estimated apparent clearance of Peginterferon alfa-2b is 22 milliters per hour per kilogram [FDA Label].

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "L03AB", "L03A", "L03", "L", "L03AB", "L03A", "L03", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "553.4", "description": "Peg-Intron 50 mcg kit", "unit": "kit" }, { "cost": "553.4", "description": "Peg-Intron redipen 50 mcg", "unit": "redipen" }, { "cost": "581.02", "description": "Peg-Intron redipen 80 mcg", "unit": "redipen" }, { "cost": "607.19", "description": "Peg-Intron 50 mcg/0.5ml Kit", "unit": "kit" }, { "cost": "609.26", "description": "Peg-Intron 80 mcg Kit", "unit": "kit" }, { "cost": "610.09", "description": "Peg-Intron redipen 120 mcg", "unit": "redipen" }, { "cost": "637.49", "description": "Peg-Intron Redipen 80 mcg/0.5ml Kit", "unit": "kit" }, { "cost": "639.74", "description": "Peg-Intron 120 mcg Kit", "unit": "kit" }, { "cost": "640.6", "description": "Peg-Intron redipen 150 mcg 4pk", "unit": "redipen" }, { "cost": "640.61", "description": "Peg-Intron redipen 150 mcg", "unit": "redipen" }, { "cost": "669.39", "description": "Peg-Intron Redipen 120 mcg/0.5ml Kit", "unit": "kit" }, { "cost": "671.74", "description": "Peg-Intron 150 mcg Kit", "unit": "kit" }, { "cost": "702.87", "description": "Peg-Intron Redipen 150 mcg/0.5ml Kit", "unit": "kit" }, { "cost": "2428.8", "description": "Peg-Intron Redipen Pak 4 4 50 mcg/0.5ml Kit Box", "unit": "kit" } ]

[ { "approved": "2008-02-19", "country": "Canada", "expires": "2025-02-19", "number": "1341567" }, { "approved": "2002-02-26", "country": "Canada", "expires": "2016-10-31", "number": "2329474" } ]

[ "Pegetron", "Pegetron", "Pegetron", "Pegetron", "Pegetron", "Pegetron", "Pegetron", "Pegetron", "Pegetron", "PegIntron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "PegIntron", "PegIntron", "PegIntron", "PegIntron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Pegintron", "Sylatron", "Sylatron", "Sylatron", "Sylatron", "Sylatron", "Sylatron", "Unitron Peg", "Unitron Peg", "Unitron Peg", "Unitron Peg", "Victrelis Triple", "Victrelis Triple", "Victrelis Triple", "Victrelis Triple" ]

[ "PEG-Intron" ]

[ "Pegetron", "Pegetron", "Pegetron", "Victrelis Triple", "Victrelis Triple", "Victrelis Triple", "Victrelis Triple", "Pegetron", "Pegetron", "Pegetron", "Pegetron", "Pegetron", "Pegetron" ]

[ "P17181", "P48551" ]

[ "P05177", "P10635", "P11712" ]

[]

DB00023

Asparaginase Escherichia coli

Asparaginase derived from _Escherichia coli_ (L-asparagine amidohydrolase, EC 3.5.1.1) is an enzyme responsible for the metabolism of L-asparagine, by catalyzing L-asparagine into L-aspartic acid and ammonia. It also facilitates the production of oxaloacetate which is needed for general cellular metabolism. Asparaginase from _E. coli_ has clinically shown to exhibit antitumor actions in models of leukaemias [A31996, A31997]. L-asparaginase of _E. coli_ is marketed under several different trade names, including Elspar, for the treatment of acute lymphoblastic leukemia (ALL) as part of a multi-agent chemotherapeutic regimen. It is available as intramuscular or intravenous injections. Therapeutic L-asparaginase from _E. coli_ works by depleting the levels of non-essential amino acid, asparagine, in lymphoblastic leukemic cells thus promoting apoptotic cell death [A31999]. For patients who develop hypersensitivity to _E. coli_-derived formulations of L-asparaginase, the use of PEGylated or non-PEGylated [DB08886] is recommended [A31999].

liquid

Indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL).[L39809]

In clinical trials of patients with previously untreated, standard-risk ALL, administration of asparaginase resulted in a decrease of plasma asparagine levels from average of 41 μM to less than 3 μM [FDA Label]. The native asparaginase in whom plasma enzyme activity before treatment was greater than 0.1 International Units/mL [FDA Label]. In this study, cerebrospinal fluid asparagine levels in patients treated with asparaginase decreased from 2.8 μM (pretreatment) to 1.0 μM and 0.3 μM at day 7 and day 28 of induction, respectively [FDA Label]. Native E. coli asparaginase results in asparagine depletion in 14 to 23 days following administration [A31999].

Asparagine is a non-essential amino acid that maintains DNA, RNA and protein synthesis and promotes cell growth. While healthy and normal cells are capable of obtaining asparagine via dietary intake or synthesizing the asparagine from aspartate via asparagine synthetase activity, lymphoblastic leukemic cells lack the asparagine synthetase enzyme and cannot produce asparagine _de novo_ [A31999]. Thus, leukemic cells rely on exogenous source of asparagine for protein synthesis and cell survival [A31999]. L-asparagine from E. coli serves to deplete plasma levels of asparagine in leukemic cells by converting L-asparagine to L-aspartic acid and ammonia [A31999], leading to reduced reduced DNA, RNA and protein synthesis; inhibition of cell growth; and ultimately the activation of apoptotic cell-death mechanisms [A31999]. Normal cells, however, are able to synthesize asparagine and thus are affected less by the rapid depletion produced by treatment with the enzyme asparaginase [FDA Label].

In a study in patients with metastatic cancer and leukemia, daily intravenous administration of L-asparaginase derived from _E. coli_ resulted in a cumulative increase in plasma levels. Following intramuscular injection in patients with metastatic cancer and leukemia, peak plasma levels of asparaginase was achieved 14 to 24 hours post-dosing [FDA Label]. Peak asparaginase activity of native _E. coli_ asparaginase can be observed in 24 to 48 hours following administration [A31999].

null

No studies assessing the mutagenic or carcinogenic potential of _E. coli_ L-asparagine have been conducted. In the Ames assay, no mutagenic effect was demonstrated when tested against Salmonella typhimurium strains [FDA Label]. No studies have been performed on impairment of fertility [FDA Label]. Following a single, intravenous injection of 12,500 to 50,000 International Units L-asparagine/kg in rabbits, edema and necrosis of pancreatic islets were observed. The clinical relevance of this finding is unclear as it does not indicate pancreatitis [FDA Label].

Plasma half life of L-asparagine derived from _E. coli_ following intravenous injection was 8-30 hrs [FDA Label]. Plasma half-life was 34 to 49 hours after intramuscular injection [FDA Label]. Half-life (mean ± SD) of native _E. coli_ asparaginase is approximately 1.28 ± 0.35 days [A31999].

null

Apparent volume of distribution was slightly greater than the plasma volume. Asparaginase levels in cerebrospinal fluid were less than 1% of concurrent plasma levels [A31999].

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L01XX", "L01X", "L01", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "74.6", "description": "Elspar 10000 unit vial", "unit": "vial" } ]

[]

[ "Elspar", "Kidrolase", "Rylaze", "Spectrila", "Spectrila" ]

[]

[ "P05543" ]

[]

DB00024

Thyrotropin alfa

Thyrotropin alfa is a recombinant form of thyroid stimulating hormone used in performing certain tests in patients who have or have had thyroid cancer. It is also used along with a radioactive agent to destroy remaining thyroid tissue in certain patients who have had their thyroid gland removed because of thyroid cancer. It is a heterodimeric glycoprotein comprised of two non-covalently linked subunits, an alpha subunit of 92 amino acid residues containing two N-linked glycosylation sites and a beta subunit of 112 residues containing one N-linked glycosylation site. The alpha subunit of thyrotropin alfa, which is the effector region responsible for the stimulation of adenylate cyclase, displays close structural similarity with the alpha subunit of human chorionic gonadotropin (hCG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). The beta subunit (TSHB) bestows its receptor specificity due to the uniqueness to TSH. The amino acid sequence of thyrotropin alfa is identical to that of human pituitary thyroid stimulating hormone.

liquid

For detection of residueal or recurrent thyroid cancer

Binding of thyrotropin alfa to TSH receptors on normal thyroid epithelial cells or on well-differentiated thyroid cancer tissue stimulates iodine uptake and organification. Thyrogen is an exogenous source of human TSH that offers an additional diagnostic tool in the follow-up of patients with a history of well-differentiated thyroid cancer.

Thyrotropin Alfa binds to the thyrotropin receptors found on any residual thyroid cells or tissues. This stimulates radioactive iodine uptake for better radiodiagnostic imaging.

Time to peak: Median: 10 hours (range: 3-24 hours) After a single intramuscular injection of 0.9 mg of thyrotropin alfa: Cmax= 116+38mU/L, Tmax=22+8.5 hours. AUC=5088+1728 mU·hr/L.

null

No difference in efficacy and toxicity between adult and geriatric patients. No studies in lactating women, pregnant women and pediatrics. Cautionary administration is advised.

25 ± 10 hours

null

kidney and liver

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "vet_approved" ]

[ "H01AB", "H01A", "H01", "H" ]

[ "Humans and other mammals" ]

[ { "cost": "1196.4", "description": "Thyrogen 1.1 mg vial", "unit": "vial" } ]

[ { "approved": "1998-11-24", "country": "United States", "expires": "2015-11-24", "number": "5840566" } ]

[ "Thyrogen", "Thyrogen", "Thyrogen", "Thyrogen", "Thyrogen" ]

[]

[ "P16473" ]

[]

DB00025

Antihemophilic factor, human recombinant

Human recombinant antihemophilic factor (AHF) or Factor VIII, 2332 residues, glycosylated, produced by CHO cells

solid

The human recombinant antihemophilic factor is indicated for use in adults and children with hemophilia A for the control and prevention of bleeding episodes, perioperative management, and routine prophylaxis to prevent or reduce the frequency of bleeding episodes.[L41025, L36130]

Antihemophilic Factor binds factor IXa along with calcium and phospholipid, This complex converts factor X to factor Xa to facilitate clotting cascade.

Antihemophilic factor (AHF) is a protein found in normal plasma which is necessary for clot formation. The administration of AHF provides an increase in plasma levels of AHF and can temporarily correct the coagulation defect of patients with hemophilia A (classical hemophilia).

null

8.4-19.3 hrs

null

* 4.1 mL/h•kg [Previously treated pediatric patients]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "B02BD", "B02B", "B02", "B" ]

[ "Humans and other mammals" ]

[ { "cost": "1.01", "description": "Monoclate-p 1000 unit kit", "unit": "kit" }, { "cost": "1.01", "description": "Monoclate-p 1500 unit kit", "unit": "kit" }, { "cost": "1.01", "description": "Monoclate-p 250 unit kit", "unit": "kit" }, { "cost": "1.01", "description": "Monoclate-p 500ahfu kit", "unit": "kit" }, { "cost": "1.2", "description": "Alphanate 1000-1500 unit vial", "unit": "vial" }, { "cost": "1.2", "description": "Alphanate 250-500 unit vial", "unit": "vial" }, { "cost": "1.2", "description": "Humate-p 1000 unit kit", "unit": "kit" }, { "cost": "1.2", "description": "Humate-p 1200 unit kit", "unit": "kit" }, { "cost": "1.2", "description": "Humate-p 2000 unit kit", "unit": "kit" }, { "cost": "1.2", "description": "Humate-p 2400 unit kit", "unit": "kit" }, { "cost": "1.2", "description": "Humate-p 500 unit kit", "unit": "kit" }, { "cost": "1.2", "description": "Humate-p 600 unit kit", "unit": "kit" }, { "cost": "1.31", "description": "Koate-dvi 1000 unit kit", "unit": "kit" }, { "cost": "1.31", "description": "Koate-dvi 250 unit kit", "unit": "kit" }, { "cost": "1.31", "description": "Koate-dvi 500 unit kit", "unit": "kit" }, { "cost": "1.31", "description": "Refacto 1000 unit vial", "unit": "vial" }, { "cost": "1.31", "description": "Refacto 2000 unit vial", "unit": "vial" }, { "cost": "1.31", "description": "Refacto 250 unit vial", "unit": "vial" }, { "cost": "1.31", "description": "Refacto 500 unit vial", "unit": "vial" }, { "cost": "1.34", "description": "Hemofil m 1701-2000 unit vial", "unit": "vial" }, { "cost": "1.34", "description": "Hemofil m 220-400 unit vial", "unit": "vial" }, { "cost": "1.34", "description": "Hemofil m 401-800 unit vial", "unit": "vial" }, { "cost": "1.34", "description": "Hemofil m 801-1700 unit vial", "unit": "vial" }, { "cost": "1.38", "description": "Wilate 450-450 unit kit", "unit": "kit" }, { "cost": "1.38", "description": "Wilate 900-900 unit kit", "unit": "kit" }, { "cost": "1.56", "description": "Helixate fs 1000 unit vial", "unit": "vial" }, { "cost": "1.56", "description": "Helixate fs 250 unit vial", "unit": "vial" }, { "cost": "1.56", "description": "Helixate fs 3000 unit vial", "unit": "vial" }, { "cost": "1.56", "description": "Helixate fs 500 unit vial", "unit": "vial" }, { "cost": "1.66", "description": "Xyntha 1000 unit kit", "unit": "kit" }, { "cost": "1.66", "description": "Xyntha 2000 unit kit", "unit": "kit" }, { "cost": "1.66", "description": "Xyntha 250 unit kit", "unit": "kit" }, { "cost": "1.66", "description": "Xyntha 500 unit kit", "unit": "kit" }, { "cost": "1.68", "description": "Advate 1201-1800 unit vial", "unit": "vial" }, { "cost": "1.68", "description": "Advate 1801-2400 unit vial", "unit": "vial" }, { "cost": "1.68", "description": "Advate 200-400 unit vial", "unit": "vial" }, { "cost": "1.68", "description": "Advate 2400-3600 unit vial", "unit": "vial" }, { "cost": "1.68", "description": "Advate 401-800 unit vial", "unit": "vial" }, { "cost": "1.68", "description": "Advate 801-1200 unit vial", "unit": "vial" }, { "cost": "1.68", "description": "Kogenate fs 1000 unit vial", "unit": "vial" }, { "cost": "1.68", "description": "Kogenate fs 250 unit vial", "unit": "vial" }, { "cost": "1.68", "description": "Kogenate fs 3000 unit vial", "unit": "vial" }, { "cost": "1.68", "description": "Kogenate fs 500 unit vial", "unit": "vial" } ]

[ { "approved": "2007-09-11", "country": "Canada", "expires": "2013-10-01", "number": "2124690" }, { "approved": "1997-09-23", "country": "Canada", "expires": "2014-09-23", "number": "1339477" } ]

[ "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Advate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Adynovate", "Esperoct", "Esperoct", "Helixate FS", "Helixate FS", "Helixate FS", "Helixate FS", "Helixate FS", "Helixate FS", "Helixate FS", "Helixate FS", "Helixate FS", "Helixate FS", "Helixate Nexgen", "Helixate Nexgen", "Helixate Nexgen", "Helixate Nexgen", "Helixate Nexgen", "Iblias", "Iblias", "Iblias", "Iblias", "Iblias", "Kogenate - Pws IV 1000I.U./vial", "Kogenate - Pws IV 250I.U./vial", "Kogenate - Pws IV 500I.U./vial", "Kogenate Bayer", "Kogenate Bayer", "Kogenate Bayer", "Kogenate Bayer", "Kogenate Bayer", "Kogenate Bayer", "Kogenate Bayer", "Kogenate Bayer", "Kogenate Bayer", "Kogenate Bayer", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS", "Kogenate FS -(with Bio-set)", "Kogenate FS -(with Bio-set)", "Kogenate Pws 1000iu/vial", "Kogenate Pws 250iu/vial", "Kogenate Pws 500iu/vial", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Kovaltry", "Novoeight", "Novoeight", "Novoeight", "Novoeight", "Novoeight", "Novoeight", "Recombinate", "Recombinate", "Recombinate", "Recombinate", "Recombinate", "Recombinate", "Recombinate", "Recombinate", "Recombinate Pws Inj 1000I.U./vial", "Recombinate Pws Inj 250I.U./vial", "Recombinate Pws Inj 500I.U./vial" ]

[ "Bioclate", "Helixate", "Hyate:C", "Koate-HP", "Kogenate", "Monarc-M", "ReFacto" ]

[]

[ "P00742", "P00740", "P04275", "O14832", "P07307", "P11021", "P27797", "P27824", "P49257", "Q07954", "Q8NI22" ]

[ "P00734", "P04070" ]

[]

DB00026

Anakinra

Anakinra is a recombinant human interleukin-1 (IL-1) receptor antagonist (IL-1Ra) composed of 153 amino acid residues. Unlike native human IL-1Ra, anakinra has an additional methionine residue at the amino terminus. This drug binds to the IL-1 receptor, competing with and inhibiting the activity of IL-1 alpha and beta.[L35415] Anakinra is indicated for the management of rheumatoid arthritis (RA) in patients 18 years of age or older who have failed one or more disease-modifying antirheumatic drugs (DMARDs), as well as the treatment of neonatal-onset multisystem inflammatory disease (NOMID) and deficiency of interleukin-1 receptor antagonist (DIRA).[L35415] Since IL-1 has an important role in inflammation and immunological responses, anakinra is also used for the off-label treatment of inflammatory diseases.[A247000] Anakinra is produced using the _E. Coli_ bacterial expression system. On November 14, 2001, it was approved by the FDA for the treatment of rheumatoid arthritis. It was later approved for the treatment of NOMID and DIRA on December 21, 2012, and December 18, 2020, respectively. A few studies have evaluated the use of anakinra for the treatment of coronavirus disease 2019 (COVID-19).[A247265] On November 8, 2022, the FDA issued an emergency use authorization (EUA) of anakinra for the treatment of COVID-19 in hospitalized patients who are at risk of progressing to severe respiratory failure.[L43932]

liquid

Anakinra is an interleukin-1 receptor antagonist indicated for the reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis (RA), in patients 18 years of age or older who have failed one or more disease-modifying antirheumatic drugs (DMARDs). Anakinra can be used alone or in combination with DMARDs other than Tumor Necrosis Factor (TNF) blocking agents.[L35415] Anakinra is also indicated for the treatment of Neonatal-Onset Multisystem Inflammatory Disease (NOMID) and the treatment of Deficiency of Interleukin-1 Receptor Antagonist (DIRA).[L35415] Anakinra is also used off-label for the treatment of several inflammatory diseases.[A247000] The FDA has issued an emergency use authorization (EUA) for the emergency use of anakinra for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adults with positive results of direct SARS-CoV-2 viral testing with pneumonia requiring supplemental oxygen (low- or high-flow oxygen) who are at risk of progressing to severe respiratory failure and likely to have an elevated plasma soluble urokinase plasminogen activator receptor (suPAR). Since anakinra is approved for this condition under EUA, the drug should only be used when there are no alternative treatment available.[L43927]

Anakinra is a recombinant human interleukin-1 receptor antagonist (IL-1Ra) that blocks the biologic activity of interleukin-1 (IL-1) by competitively inhibiting its ability to bind to the IL-1 type I receptor (IL-1RI). IL-1 production is higher in inflammatory diseases such as rheumatoid arthritis, where the amount of naturally occurring IL-1Ra cannot compete with the high level of IL-1 present.[L35415] Anakinra has been associated with a higher probability of developing a severe infection, and the use of TNF blocking agents can increase this incidence.[L35415] Hypersensitivity reactions have been reported in patients using anakinra. The prevalence of allergic reactions may be higher in patients with deficiency of interleukin-1 receptor antagonist (DIRA), since they lack the naturally occurring IL-1Ra.[L35415] Anakinra can also decrease neutrophil counts in patients. Therefore, neutrophil counts should be assessed before initiating anakinra.[L35415]

Interleukin-1 (IL-1) plays an important role in inflammation and immunological responses. Inflammatory stimuli trigger its production, and it binds to the IL-1 receptor to activate a wide variety of mechanisms. The activity of the IL-1 receptor is also regulated by a naturally occurring IL-1 receptor antagonist (IL-1Ra) that competes for the binding sites of the IL-1 receptor.[L35415] In rheumatoid arthritis (RA) patients, IL-1 levels are elevated, inducing cartilage degradation and the stimulation of bone resorption, and the amount of IL-1Ra in the synovium and synovial fluid of RA patients cannot compete with the high level of IL-1 present.[L35415] Anakinra is a recombinant, non-glycosylated form of IL-1Ra that competes with and inhibits IL-1 by binding to the IL-1 receptor; therefore, the administration of this drug reduces the inflammatory response in RA patients.[A246908,L35415] Anakinra can also be used in the treatment of neonatal-onset multisystem inflammatory disease (NOMID) and deficiency of interleukin-1 receptor antagonist (DIRA).[L35415] Patients with NOMID have spontaneous mutations in CIAS1/NLRP3, a gene that encodes cryopyrin, an inflammasome component. When activated, the inflammasome enhances and promotes the production of IL-1β, an isoform of IL-1.[A246898,L35415] DIRA is an autoinflammatory disease caused by mutations in the IL1RN gene. These mutations reduce the amount of IL-1Ra that is secreted, leading to the unopposed action of IL-1.[L35415] Anakinra controls NOMID and DIRA symptoms by inhibiting IL-1 activity.[L35415]

The bioavailability of anakinra is 95% in healthy subjects administered a 70 mg subcutaneous bolus injection. In patients with rheumatoid arthritis (RA) administered a subcutaneous dose of anakinra, the maximum plasma concentration was detected 3 to 7 hours later. No unexpected accumulation was observed in RA patients receiving this drug for up to 24 weeks.[L35415] In a phase 1, single-center, randomized, sequential single-dose escalation PK study done in patients with stable RA, AUC increased in a relatively dose-proportional manner. While the tmax and Cmax fluctuated across the different doses provided to these patients (range from 0.5 to 6 mg/kg), clearance appeared to be consistent.[L41628] In patients with neonatal-onset multisystem inflammatory disease (NOMID) treated with a subcutaneous dose of 3 mg/kg of anakinra for an average of 3.5 years (n=16), Cmax was 3628 ng/mL and C24h was 203 ng/mL.[L35415]

As a protein-based therapy, anakinra is expected to be metabolized by proteases throughout the body.

In clinical trials done in patients with rheumatoid arthritis (RA) and neonatal-onset multisystem inflammatory disease (NOMID) treated with anakinra, no cases of overdose were reported.[L35415] Sepsis trials were performed using mean calculated doses up to 35 times the ones given to patients with RA over 72 hours. Anakinra did not produce any serious toxicities at this dose range.[L35415] In preclinical studies done in rats, where up to 100 mg/kg/day were administered either intravenously or subcutaneously over 14 days, and given at doses of 2, 20 or 200 mg/kg/day subcutaneously for 6 months, anakinra was well tolerated. Toxicity ranged from mild to moderate, and dose-related inflammation, hemorrhage and fibrosis at the injection site were detected in both rats and monkeys.[L41634] The no observable adverse effect level (NOAEL) in rats receiving a daily subcutaneous dose of anakinra for 6 months was 2 mg/kg/day. In rats receiving a daily intravenous injection of anakinra for 14 or 28 days, the NOAEL was 30 mg/kg/day. The NOAEL in Rhesus monkeys was 150 mg/kg/day when anakinra was administered via intravenous infusion for 7 days, 10-30 mg/kg/day when administered via intravenous bolus injection for 14 days and 5 mg/kg/day when administered subcutaneously for 14 days.[L41634] Anakinra had no effects on fertility and reproductive capacity in both male and female rats given the maximum recommended human dose.[L35415]

In patients with rheumatoid arthritis (RA), the terminal half-life of anakinra ranged from 4 to 6 hours. In patients with neonatal-onset multisystem inflammatory disease (NOMID), the median half-life of anakinra was 5.7 h (range=3.1-28.2, n=12).[L35415]

Not Available

Anakinra is mostly excreted by the kidney; therefore, the risk of toxic reactions may increase in patients with impaired renal function.[L35415]

In adult subjects with rheumatoid arthritis (RA) treated with anakinra (n=35), the volume of distribution averaged 18.5 L.[L41628]

In patients with rheumatoid arthritis (RA), the clearance of anakinra was relatively consistent for different dose levels.[L41628] Clearance is variable and increases with increasing creatinine clearance and body weight. However, gender and age were not significant factors.[L35415] In patients with mild (creatinine clearance 50-80 mL/min) and moderate (creatinine clearance 30-49 mL/min) renal impairment, the mean plasma clearance of anakinra was 16% and 50% lower, respectively. In patients with severe renal insufficiency and end-stage renal disease (creatinine clearance < 30 mL/min), the mean plasma clearance of anakinra was 70% and 75% lower, respectively.[L35415]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L04AC", "L04A", "L04", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "61.8", "description": "Kineret 100 mg/0.67 ml syr", "unit": "syringe" }, { "cost": "449.9", "description": "Kineret 1 Box = 7 Syringes, 4.69ml Box", "unit": "box" } ]

[ { "approved": "2008-04-08", "country": "Canada", "expires": "2013-09-17", "number": "2141953" }, { "approved": "2001-11-27", "country": "Canada", "expires": "2018-11-27", "number": "1341322" } ]

[ "Kineret", "Kineret", "Kineret", "Kineret", "Kineret", "Kineret", "Kineret", "Kineret" ]

[]

[ "P14778" ]

[]

DB00027

Gramicidin D

Gramcidin D is a heterogeneous mixture of three antibiotic compounds, gramicidins A, B and C, making up 80%, 6%, and 14% respectively all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramcidins are 15 residue peptides with alternating D and L amino acids, which assemble inside of the hydrophobic interior of the cellular lipid bilayer to form a β-helix. Active against most Gram-positive bacteria and some Gram-negative organisms, Gramicidin D is used primarily as a topical antibiotic and is also found in Polysporin ophthalmic solution.

liquid

For treatment of skin lesions, surface wounds and eye infections.

Gramicidin is particularly effective against gram-positive bacteria. Because the drug is highly hemolytic, it cannot be administered internally and so is used only on the skin as a lotion or ointment. It is used primarily in the treatment of infected surface wounds, and in eye, nose, and throat infections. It is normally given with two other antibiotics (neomycin and polymixin B) as an ophthalmic solution.

Gramicidin D binds to and inserts itself into bacterial membranes (with a strong preference to gram-positive cell membranes). This results in membrane disruption and permeabilization (it acts as a channel). This leads to (i) loss of intracellular solutes (e.g., K+ and amino acids); (ii) dissipation of the transmembrane potential; (iii) inhibition of respiration; (iv) a reduction in ATP pools; and (v) inhibition of DNA, RNA, and protein synthesis, which leads to cell death.

null

Organic compounds

Organic Polymers

Polypeptides

null

[ "approved" ]

[ "R02AB", "R02A", "R02", "R" ]

[ "Staphylococcus aureus", "Streptococcus agalactiae", "Streptococcus pneumoniae", "Escherichia coli", "Haemophilus influenzae", "Klebsiella", "Enterobacter", "Neisseria gonorrhoeae", "Neisseria meningitidis", "Pseudomonas aeruginosa" ]

[ { "cost": "23.12", "description": "Neosporin gu irr 40 mg/ml amp", "unit": "ml" }, { "cost": "240.0", "description": "Gramicidin d powder", "unit": "g" }, { "cost": "0.32", "description": "Neosporin + pain relief cream", "unit": "g" } ]

[]

[ "Antibiotic Cream", "Antibiotic Cream", "Antibiotic Cream", "Antibiotic Cream for Kids", "Antibiotic Cream for Kids", "Antibiotic Cream Plus Pain Relief", "Antibiotic Cream Plus Pain Relief", "Antibiotic Cream Plus Pain Relief for Kids", "Antibiotic Drops", "Antibiotic Ear Drops", "Antibiotic Eye Drops", "Antibiotic Plus Pain Relief Cream", "Complete Antibiotic Ointment", "Kenacomb Cream", "Kenacomb Mild Cream", "Kenacomb Mild Ointment", "Kenacomb Ointment", "Kenacomb Ont", "Lidecomb Cream", "Lidosporin Cream", "Lidosporin Cream", "Mecomb Crm 0.1%", "Neocidin", "Neomycin and Polymyxin B Sulfates and Gramicidin", "Neomycin and Polymyxin B Sulfates and Gramicidin", "Neomycin and Polymyxin B Sulfates and Gramicidin", "Neomycin and Polymyxin B Sulfates and Gramicidin", "Neomycin and Polymyxin B Sulfates and Gramicidin", "Neomycin and Polymyxin B Sulfates and Gramicidin", "Neomycin and Polymyxin B Sulfates and Gramicidin", "Neosporin", "Neosporin", "Neosporin Antibiotic Cream", "Neosporin Eye-ear Solution", "Odan-spor", "Optimyxin", "Optimyxin Plus", "Original Antibiotic Cream", "Original Antibiotic Cream", "Polycidin Eye, Ear Drops", "Polysporin Antibiotic Burn Cream", "Polysporin Antibiotic Cream", "Polysporin Burn Formula Cream", "Polysporin Cold Sore Ointment", "Polysporin Complete", "Polysporin Cream", "Polysporin Eye and Ear Drops Sterile", "Polysporin Eye and Ear Drops Sterile", "Polysporin for Kids", "Polysporin for Stitches", "Polysporin Plus Pain Relief", "Polysporin Triple Antibiotic Ointment", "Polysporin Triple Antibiotic Ointment", "Polysporin Triple Antibiotic Ointment", "Polytopic Cream", "Sandoz Opticort", "Sofracort", "Sofracort Ear/eye Ointment", "Sofracort Eye/ear Drops", "Sofracort Sterile Ear/eye Drops", "Sofracort Sterile Ear/eye Ointment", "Sofracort Sterile Ear/eye Ointment", "Soframycin Nasal Spray", "Soframycin Nasal Spray", "Soframycin Nasal Spray", "Soframycin Ointment", "Soframycin Skin Ointment", "Soframycin Skin Ointment", "Soothe Antibiotic Drops", "Teva-triacomb", "Theraderm Cream", "Triple Antibiotic Ointment", "Triple Antibiotic Ointment", "Triple Antibiotic Ointment", "Triple Antibiotic Ointment", "Triple Antibiotic Ointment", "Viaderm Kc Crm", "Viaderm Kc Ont" ]

[ "Sofradex" ]

[ "Neomycin and Polymyxin B Sulfates and Gramicidin", "Neomycin and Polymyxin B Sulfates and Gramicidin", "Neomycin and Polymyxin B Sulfates and Gramicidin", "Neosporin", "Neomycin and Polymyxin B Sulfates and Gramicidin", "Neomycin and Polymyxin B Sulfates and Gramicidin", "Neomycin and Polymyxin B Sulfates and Gramicidin", "Neocidin", "Neomycin and Polymyxin B Sulfates and Gramicidin", "Neosporin", "Soframycin Nasal Spray", "Triple Antibiotic Ointment", "Complete Antibiotic Ointment", "Antibiotic Cream", "Antibiotic Cream for Kids", "Original Antibiotic Cream", "Antibiotic Cream Plus Pain Relief", "Antibiotic Cream", "Antibiotic Cream Plus Pain Relief", "Antibiotic Cream Plus Pain Relief for Kids", "Soframycin Nasal Spray", "Kenacomb Mild Cream", "Kenacomb Cream", "Soframycin Skin Ointment", "Kenacomb Mild Ointment", "Kenacomb Ointment", "Soframycin Nasal Spray", "Antibiotic Cream", "Sofracort Sterile Ear/eye Ointment", "Lidecomb Cream", "Soframycin Ointment", "Antibiotic Cream for Kids", "Triple Antibiotic Ointment", "Original Antibiotic Cream", "Antibiotic Drops", "Soframycin Skin Ointment", "Antibiotic Plus Pain Relief Cream", "Sofracort Eye/ear Drops", "Sofracort Sterile Ear/eye Ointment", "Sofracort Ear/eye Ointment", "Theraderm Cream", "Polysporin Antibiotic Cream", "Polytopic Cream", "Polysporin Triple Antibiotic Ointment", "Polysporin Eye and Ear Drops Sterile", "Polysporin Plus Pain Relief", "Polysporin Complete", "Triple Antibiotic Ointment", "Polysporin for Kids", "Viaderm Kc Crm", "Viaderm Kc Ont", "Polysporin Eye and Ear Drops Sterile", "Polysporin Cream", "Lidosporin Cream", "Polysporin Burn Formula Cream", "Kenacomb Ont", "Polysporin Triple Antibiotic Ointment", "Mecomb Crm 0.1%", "Polycidin Eye, Ear Drops", "Polysporin Antibiotic Burn Cream", "Polysporin Triple Antibiotic Ointment", "Lidosporin Cream", "Neosporin Antibiotic Cream", "Neosporin Eye-ear Solution", "Polysporin for Stitches", "Optimyxin", "Polysporin Cold Sore Ointment", "Triple Antibiotic Ointment", "Odan-spor", "Sandoz Opticort", "Triple Antibiotic Ointment", "Antibiotic Ear Drops", "Antibiotic Eye Drops", "Optimyxin Plus", "Teva-triacomb", "Sofracort", "Sofracort Sterile Ear/eye Drops", "Soothe Antibiotic Drops" ]

[]

[ "P08183" ]

DB00028

Human immunoglobulin G

Intravenous immunoglobulin (IVIg) is a mixture of IgG1 and other antibodies derived from healthy human plasma via Cohn fractionation. The purification process includes cold alcohol fractionation, polyethylene glycol precipitation, and ion exchange chromatography. IVIg contains the same distribution of IgG antibody subclasses as is found in the general human population. IgG subclasses are fully represented in the following proportions: 70.3% IgG1, 24.7% IgG2, 3.1% IgG3, and 1.9% IgG4. IVIg is used in the treatment of immunodeficiencies, as well as autoimmune and inflammatory disorders.

liquid

Human immunoglobulin G is indicated for the following conditions: ### Primary Immunodeficiency - for the treatment of primary immunodeficiency in adult and pediatric patients[L39920, L39930, L39935, L39940, L39945, L39950, L39955, L39960, L39965, L39975, L39980, L40029, L40034, L40044] - in combination with [hyaluronidase (human recombinant)] for the treatment of primary immunodeficiency in patients ≥2 years of age.[L42760] ### Immune Thrombocytopenic Purpura (ITP) - for the treatment of acute or chronic immune thrombocytopenic purpura in adult and pediatric patients[L39940, L39950, L39960, L39965, L39970, L39975, L39980] ### Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) - for the treatment of CIDP in adult patients[L39955, L39965, L39975, L39980, L40034] - in combination with hyaluronidase (human recombinant) as a maintenance therapy in adults with chronic inflammatory demyelinating polyneuropathy (CIDP)[L40039] ### Multifocal Motor Neuropathy (MMN) - for maintenance therapy to improve muscle strength and disability in adult patients with MMN[L39955] ### Prophylaxis of Bacterial Infection - for the prevention of bacterial infections in patients with hypogammaglobulinemia and/or B-cell chronic lymphocytic leukemia[L39960] ### Coronary Artery Aneurysm Associated With Kawasaki Syndrome - for the prevention of coronary artery aneurysms in pediatric patients with Kawasaki syndrome[L39960] ### Dermatomyositis - for the treatment of dermatomyositis in adult patients[L39970]

Used as a replacement therapy in inherited humoral immunodeficiency disorders such as severe combined immunodeficiency syndrome, x-linked agammaglobulinemia, and Wiskott-Aldrich Syndrome. The immunoglobulins target, bind and kill bacterial cells as well as viral particles. IgG is the monomeric immunoglobulin of which there are four subclasses (IgG1, IgG2, IgG3 and IgG4) in differing abundances (66%, 23%, 7% and 4%). IgAs represent about 15% of the immunoglobulins in the blood. These target inhaled or ingested pathogens.

IVIg interacts with a number of different components of the immune system, including cytokines, complement, Fc receptors and several cell surface immunocompetent molecules. IVIg also impacts different effector cells of the immune system (B and T lymphocytes, dendritic cells, etc.) and regulates a wide range of genes. Its main mechanism of actions are believed to be Fc-dependent and F(ab')2-dependent. IVIg competitively blocks gamma Fc receptors, preventing the binding and ingestion of phagocytes and suppressing platelet depletion. IVIg contains a number of different antobodies, which prevent infection by attaching to the surface of invading pathogens and aiding in their disposal before they can infect cells. Antibodies remove pathogens via complement activation, agglutination or precipitation, pathogen receptor blocking, macrophage “tagging” or neutralization (via binding) of pathogen toxins. Intact IVIg and F(ab′)2 fragments of IVIg can also neutralize the activity of various autoantibodies. By triggering the production of interleukin-1 receptor antagonist, IVIg modulates of the production of cytokines and cytokine antagonists. It also prevents the generation of the C5b-9 membrane attack complex and subsequent complement-mediated tissue damage by binding active complement components.

null

>20 hours (mammalian reticulocytes, in vitro).

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[]

[ "Humans and other mammals", "Bacteria and protozoa", "Various viruses" ]

[ { "cost": "4.84", "description": "Flebogamma 5% vial", "unit": "ml" }, { "cost": "4.84", "description": "Flebogamma dif 5% vial", "unit": "ml" }, { "cost": "9.34", "description": "Immune globulin vial", "unit": "ml" }, { "cost": "11.6", "description": "Gamunex 10% vial", "unit": "ml" }, { "cost": "13.79", "description": "Gammagard liquid 10% vial", "unit": "ml" }, { "cost": "24.44", "description": "Gamastan s-d vial", "unit": "ml" }, { "cost": "30.24", "description": "Hizentra 1 gram/5 ml vial", "unit": "ml" }, { "cost": "30.24", "description": "Hizentra 2 gram/10 ml vial", "unit": "ml" }, { "cost": "30.24", "description": "Hizentra 4 gram/20 ml vial", "unit": "ml" }, { "cost": "165.04", "description": "Hyperhep b s-d vial", "unit": "ml" }, { "cost": "176.34", "description": "Nabi-hb vial", "unit": "ml" }, { "cost": "224.07", "description": "Hyperrab s-d vial", "unit": "ml" }, { "cost": "324.23", "description": "Hypertet s-d 250 unit syringe", "unit": "syringe" } ]

[]

[ "Alyglo", "Asceniv", "Bivigam", "Bivigam", "Bivigam", "Bivigam", "Bivigam", "Carimune Nanofiltered", "Carimune Nanofiltered", "Carimune Nanofiltered", "Cutaquig", "Cutaquig", "Cutaquig", "Cutaquig", "Cutaquig", "Cutaquig", "Cutaquig", "Cutaquig", "Cutaquig", "Cutaquig", "Cutaquig", "Cutaquig", "Cutaquig", "Cuvitru", "Cuvitru", "Flebogamma", "Flebogamma 10%", "Flebogamma 5%", "Flebogamma DIF", "Flebogamma Dif", "Flebogamma Dif", "Flebogamma Dif", "Flebogamma Dif", "Flebogamma Dif", "Flebogamma Dif", "Flebogamma Dif", "Flebogamma Dif", "Flebogamma Dif", "GamaSTAN", "Gamastan", "Gamastan", "Gamastan", "Gamastan S/d", "Gamimune N 10% (iv)", "Gamimune N 5% (iv)", "Gamimune N Inj 5% (iv)", "GAMMAGARD Liquid", "GAMMAGARD Liquid", "Gammagard S/d", "Gammagard S/d", "Gammagard S/d", "Gammagard S/d", "Gammagard S/d", "Gammagard S/d", "Gammagard S/d", "Gammagard S/d", "Gammagard S/d", "Gammagard S/d", "Gammagard S/d (iv)", "Gammaked", "Gammaplex", "Gammaplex", "Gammar Inj 165mg/ml", "Gamunex", "Gamunex", "Gamunex-C", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hizentra", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Igivnex", "Immune Globulin Intravenous (human) 5%", "Immune Globulin Intravenous (human), 10%", "Immune Globulin Intravenous (human), 5%", "Immune Serum Globulin (human)", "Iveegam Immuno 5000mg (iv)", "Iypoly", "Iypoly", "Kiovig", "Kiovig", "Kiovig", "Kiovig", "Kiovig", "Kiovig", "Octagam", "Octagam 5%", "Octagam Immune Globulin (Human)", "Octagam Immune Globulin (Human)", "Octagam Immune Globulin (Human)", "Octagam Immune Globulin (Human)", "Octagam Immune Globulin (Human)", "Octagam Immune Globulin (Human)", "Octagam Immune Globulin (Human)", "Octagam Immune Globulin (Human)", "Octagam Immune Globulin (Human)", "Octagam Immune Globulin (Human)", "Octagam Immune Globulin (Human)", "Octagam Immune Globulin (Human)", "Octagam Immune Globulin (Human)", "Panzyga", "Panzyga", "Panzyga", "Panzyga", "Panzyga", "Panzyga", "Panzyga", "Panzyga", "Panzyga", "Privigen", "Privigen", "Privigen", "Privigen", "Privigen", "Privigen", "Privigen", "Privigen", "Privigen", "Privigen", "Privigen", "Privigen", "Sandoglobulin Nf Liquid", "Vivaglobin", "Vivaglobin", "Winrho", "Winrho", "Winrho", "Winrho", "Winrho", "Xembify", "Xembify" ]

[ "ClairYg" ]

[ "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Iveegam Immuno 5000mg (iv)", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Iypoly", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia", "Hyqvia" ]

[ "P12314", "Q92637", "P12318", "P31994", "P31995", "P08637", "O75015", "P01024", "P0C0L4", "P0C0L5", "P01031" ]

[]

DB00029

Anistreplase

Human tissue plasminogen activator, purified, glycosylated, 527 residues purified from CHO cells. Eminase is a lyophilized (freeze-dried) formulation of anistreplase, the p-anisoyl derivative of the primary Lys-plasminogen-streptokinase activator complex (a complex of Lys-plasminogen and streptokinase). A p-anisoyl group is chemically conjugated to a complex of bacterial-derived streptokinase and human Plasma-derived Lys-plasminogen proteins.

liquid

For lysis of acute pulmonary emboli, intracoronary emboli and management of myocardial infarction

Anistreplase cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action. This helps eliminate blood clots or arterial blockages that cause myocardial infarction.

Anistreplase cleaves the Arg/Val bond in plasminogen to form plasmin. This in turn leads to the degradation of blood clots.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "B01AD", "B01A", "B01", "B" ]

[ "Humans and other mammals" ]

[]

[ "Eminase 30 Units" ]

[ "Eminase" ]

[]

[ "P00747", "P02671", "P05121" ]

[]

DB00030

Insulin human

Human Insulin, also known as Regular Insulin, is a short-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Human insulin is produced by recombinant DNA technology and is identical to endogenously produced insulin. Typically prescribed for the management of diabetes mellitus, insulin is a peptide hormone produced by beta cells of the pancreas that promotes glucose metabolism. Insulin is released from the pancreas following a meal to promote the uptake of glucose from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscle. Absorption of glucose into cells allows for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, enhances protein synthesis, and inhibits lipolysis and proteolysis among many other functions. Insulin is an important treatment in the management of Type 1 Diabetes (T1D) which is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting in the body not being able to produce or synthesize the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin to lower glucose levels in the blood. Insulin is also used in the treatment of Type 2 Diabetes (T2D), another form of diabetes mellitus that is a slowly progressing metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Without treatment or improvement in non-pharmacological measures such as diet and exercise to lower blood glucose, high blood sugar eventually causes cellular resistance to endogenous insulin, and in the long term, damage to pancreatic islet cells. Insulin is typically prescribed later in the course of T2D, after trying several oral medications such as [DB00331], [DB01120], or [DB01261] have been tried, when sufficient damage has been caused to pancreatic cells that the body is no longer able to produce insulin on its own. Marketed as the brand name product Humulin R or Novolin R, human insulin begins to exert its effects within 30 minutes of subcutaneous administration, while peak levels occur 3-4 hours after administration. Due to its quick onset of action, human insulin is considered "bolus insulin" as it provides high levels of insulin in a short period of time to mimic the release of endogenous insulin from the pancreas after meals. Bolus insulin is often combined with once daily, long-acting "basal insulin" such as [DB01307], [DB09564], and [DB00047] to provide low concentrations of background insulin that can keep blood sugar stable between meals or overnight. Use of basal and bolus insulin together is intended to mimic the pancreas' production of endogenous insulin, with a goal of avoiding any periods of hypoglycemia. Human insulin is also available in an inhalable form, intended to be used as a bolus meal-time insulin. Exubera was the first inhaled insulin available on the market and was developed by Inhale Therapeutics (later named Nektar Therapeutics). Unfortunately, limited uptake by physicians and patients, poor sales, bulky packaging, and concerns over the possible impact on lung cancer development resulted in Exubera products being withdrawn from the US markets [A176005]. Exubera was followed by Afrezza, a monomeric inhaled insulin developed by Mannkind Corporation, which received FDA approval in 2016. While still available in the US, Afrezza has had similar concerns associated with its use, and had an FDA "black box" warning added to it to warn about use in patients with chronic lung disease. Afrezza does not currently have Health Canada or European Medicines Agency approval for marketing in Canada or the EU. Human Insulin is a 51 residue peptide hormone produced by recombinant DNA technology by inserting the human insulin gene into Escherichia coli bacteria or Saccharomyces cerevisiae. The structure is identical to native human insulin, with two amino acid chains covalently linked by disulfide bonds. Human insulin is also available in an intermediate-acting form as NPH (Neutral Protamine Hagedorn) as the marketed products Novolin N and Humulin N. NPH insulin is provided as a crystalline suspension of insulin with protamine and zinc, resulting in an onset of action in 1 to 3 hours, duration of action up to 24 hours, and peak action from 6 to 8 hours. Due to the added crystals, NPH insulin is typically cloudy when compared to other forms of insulin and has a neutral pH. Without an adequate supply of insulin to promote absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high levels and can result in symptoms such as fatigue, headache, blurred vision, and increased thirst. If left untreated, the body starts to break down fat, instead of glucose, for energy which results in a build-up of ketone acids in the blood and a syndrome called ketoacidosis, which is a life-threatening medical emergency. In the long term, elevated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy.

liquid

Human insulin is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus.

Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis).

The primary activity of insulin is the regulation of glucose metabolism. Insulin promotes glucose and amino acid uptake into muscle and adipose tissues, and other tissues except brain and liver. It also has an anabolic role in stimulating glycogen, fatty acid, and protein synthesis. Insulin inhibits gluconeogenesis in the liver. Insulin binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism and catabolism.

When injected subcutaneously, the glucose-lowering effect of human insulin begins approximately 30 minutes post-dose. After a single subcutaneous administration of 0.1 unit/kg of human insulin to healthy subjects, peak insulin concentrations occurred between 1.5 to 2.5 hours post-dose. When administered in an inhaled form (as the product Afrezza), the time to maximum serum insulin concentration ranges from 10-20 minutes after oral inhalation of 4 to 48 units of human insulin. Serum insulin concentrations declined to baseline by approximately 60-240 minutes for these dose levels. Intrapatient variability in insulin exposure measured by AUC and Cmax is approximately 16% (95% CI 12-23%) and 21% (95% CI 16-30%), respectively.

The metabolism and elimination of orally inhaled human insulin are comparable to regular human insulin.

null

Systemic insulin disposition (apparent terminal half-life) following oral inhalation of 4 to 48 units of human insulin was 120-206 minutes.

null

Following oral inhalation of human insulin, a mean of 39% of the inhaled dose of carrier particles was distributed to the lungs and a mean of 7% of the dose was swallowed. The swallowed fraction was not absorbed from the GI tract and was eliminated unchanged in the feces.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "A10AC", "A10A", "A10", "A", "A10AE", "A10A", "A10", "A", "A10AB", "A10A", "A10", "A", "A10AD", "A10A", "A10", "A", "A10AF", "A10A", "A10", "A" ]

[ "Humans and other mammals" ]

[ { "cost": "2.14", "description": "Novolin Ge Nph 100 unit/ml", "unit": "cartridge" }, { "cost": "2.14", "description": "Novolin Ge Toronto 100 unit/ml", "unit": "cartridge" }, { "cost": "2.29", "description": "Humulin N 100 unit/ml", "unit": "cartridge" }, { "cost": "2.29", "description": "Humulin R 100 unit/ml", "unit": "cartridge" }, { "cost": "2.78", "description": "Novolin Ge Nph Penfill 100 unit/ml Cartridge", "unit": "cartridge" }, { "cost": "2.8", "description": "Novolin Ge Toronto Penfill 100 unit/ml Cartridge", "unit": "cartridge" }, { "cost": "2.99", "description": "Humulin N Cartridge 100 unit/ml Cartridge", "unit": "cartridge" }, { "cost": "2.99", "description": "Humulin R Cartridge 100 unit/ml Cartridge", "unit": "cartridge" }, { "cost": "24.17", "description": "NovoLIN R InnoLet 100 unit/ml Solution 3ml Cartridge", "unit": "cartridge" }, { "cost": "33.33", "description": "Novolin r 100 unit/ml cartridg", "unit": "ml" }, { "cost": "73.19", "description": "NovoLIN R 100 unit/ml Solution 10ml Vial", "unit": "vial" }, { "cost": "162.26", "description": "NovoLIN R PenFill 100 unit/ml Solution Five 3ml Cartridges Per Box = 15ml", "unit": "cartridge" } ]

[ { "approved": "2002-10-08", "country": "United States", "expires": "2010-02-12", "number": "RE37872" }, { "approved": "2007-10-30", "country": "Canada", "expires": "2015-02-07", "number": "2183577" }, { "approved": "2007-10-09", "country": "Canada", "expires": "2017-05-07", "number": "2253393" }, { "approved": "2007-11-06", "country": "United States", "expires": "2024-08-09", "number": "7291132" }, { "approved": "2001-07-10", "country": "United States", "expires": "2019-05-14", "number": "6257233" }, { "approved": "2003-04-15", "country": "United States", "expires": "2019-05-14", "number": "6546929" }, { "approved": "2004-02-03", "country": "United States", "expires": "2018-09-11", "number": "6685967" }, { "approved": "2003-06-24", "country": "United States", "expires": "2020-06-24", "number": "6582728" }, { "approved": "2014-12-16", "country": "United States", "expires": "2029-06-12", "number": "8912193" }, { "approved": "2010-01-19", "country": "United States", "expires": "2020-06-29", "number": "7648960" }, { "approved": "2003-11-25", "country": "United States", "expires": "2020-06-29", "number": "6652885" }, { "approved": "2012-09-04", "country": "United States", "expires": "2029-08-11", "number": "8258095" }, { "approved": "2014-07-15", "country": "United States", "expires": "2030-06-11", "number": "8778403" }, { "approved": "2002-09-03", "country": "United States", "expires": "2020-06-29", "number": "6444226" }, { "approved": "2011-05-17", "country": "United States", "expires": "2026-08-10", "number": "7943572" }, { "approved": "2012-02-21", "country": "United States", "expires": "2029-08-11", "number": "8119593" }, { "approved": "2011-05-17", "country": "United States", "expires": "2020-06-29", "number": "7943178" }, { "approved": "2014-11-18", "country": "United States", "expires": "2020-06-29", "number": "8889099" }, { "approved": "2014-01-07", "country": "United States", "expires": "2029-09-18", "number": "8623817" }, { "approved": "2013-03-05", "country": "United States", "expires": "2020-06-29", "number": "8389470" }, { "approved": "2015-11-24", "country": "United States", "expires": "2029-06-12", "number": "9192675" }, { "approved": "2012-07-10", "country": "United States", "expires": "2022-11-24", "number": "8215300" }, { "approved": "2012-04-03", "country": "United States", "expires": "2023-04-24", "number": "8146588" }, { "approved": "2015-02-10", "country": "United States", "expires": "2021-07-20", "number": "8950397" }, { "approved": "2013-07-16", "country": "United States", "expires": "2030-03-25", "number": "8485180" }, { "approved": "2016-03-15", "country": "United States", "expires": "2026-09-14", "number": "9283193" }, { "approved": "2014-01-28", "country": "United States", "expires": "2032-07-12", "number": "8636001" }, { "approved": "2013-04-23", "country": "United States", "expires": "2031-10-17", "number": "8424518" }, { "approved": "2013-10-08", "country": "United States", "expires": "2030-06-11", "number": "8551528" }, { "approved": "2008-12-16", "country": "United States", "expires": "2023-03-02", "number": "7464706" }, { "approved": "2014-05-20", "country": "United States", "expires": "2028-12-26", "number": "8729019" }, { "approved": "2007-12-11", "country": "United States", "expires": "2023-01-16", "number": "7305986" }, { "approved": "2013-08-06", "country": "United States", "expires": "2032-02-19", "number": "8499757" }, { "approved": "2012-04-17", "country": "United States", "expires": "2023-01-16", "number": "8156936" }, { "approved": "2014-05-27", "country": "United States", "expires": "2030-06-11", "number": "8734845" }, { "approved": "2012-07-24", "country": "United States", "expires": "2031-03-08", "number": "8227409" }, { "approved": "2016-07-19", "country": "United States", "expires": "2029-07-04", "number": "9393372" }, { "approved": "2016-05-17", "country": "United States", "expires": "2029-10-20", "number": "9339615" }, { "approved": "2016-12-06", "country": "United States", "expires": "2030-02-16", "number": "9511198" }, { "approved": "2017-03-21", "country": "United States", "expires": "2031-10-08", "number": "9597374" }, { "approved": "2016-06-07", "country": "United States", "expires": "2031-02-15", "number": "9358352" }, { "approved": "2016-09-20", "country": "United States", "expires": "2029-06-12", "number": "9446133" }, { "approved": "2017-05-30", "country": "United States", "expires": "2029-06-12", "number": "9662461" }, { "approved": "2017-08-01", "country": "United States", "expires": "2026-09-14", "number": "9717689" }, { "approved": "2018-04-17", "country": "United States", "expires": "2029-08-11", "number": "9943571" }, { "approved": "2018-08-14", "country": "United States", "expires": "2029-08-11", "number": "10046031" }, { "approved": "2019-02-12", "country": "United States", "expires": "2030-08-02", "number": "10201672" }, { "approved": "2019-07-09", "country": "United States", "expires": "2029-06-12", "number": "10342938" }, { "approved": "2019-12-10", "country": "United States", "expires": "2030-11-02", "number": "10500159" } ]

[ "Actraphane 30", "Actraphane 30", "Actraphane 30", "Actraphane 30", "Actraphane 30", "Actraphane 30", "Actraphane 30 Flexpen", "Actraphane 30 Flexpen", "Actraphane 30 Flexpen", "Actraphane 30 Innolet", "Actraphane 30 Innolet", "Actraphane 30 Innolet", "Actraphane 30 Penfill", "Actraphane 30 Penfill", "Actraphane 30 Penfill", "Actraphane 40 Penfill", "Actraphane 40 Penfill", "Actraphane 40 Penfill", "Actraphane 50 Penfill", "Actraphane 50 Penfill", "Actraphane 50 Penfill", "Actrapid", "Actrapid", "Actrapid", "Actrapid", "Actrapid", "Actrapid", "Actrapid Flexpen", "Actrapid Flexpen", "Actrapid Flexpen", "Actrapid Innolet", "Actrapid Innolet", "Actrapid Innolet", "Actrapid Penfill", "Actrapid Penfill", "Actrapid Penfill", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Entuzity Kwikpen", "Exubera", "Exubera", "Exubera", "Exubera", "Humalog 70/30", "Humulin 10/90 Cartridge", "Humulin 10/90 Cartridge", "Humulin 10/90 Inj", "Humulin 10/90 Inj", "Humulin 20/80 Cartridge", "Humulin 20/80 Cartridge", "Humulin 20/80 Inj", "Humulin 20/80 Inj", "Humulin 30/70 (insulin Human Biosynth Inj)", "Humulin 30/70 (insulin Human Biosynth Inj)", "Humulin 30/70 Cartridge", "Humulin 30/70 Cartridge", "Humulin 40/60 Cartridge", "Humulin 40/60 Cartridge", "Humulin 40/60 Inj", "Humulin 40/60 Inj", "Humulin 50/50", "Humulin 50/50 Cartridge", "Humulin 50/50 Cartridge", "Humulin 50/50 Inj", "Humulin 50/50 Inj", "Humulin 70/30", "Humulin 70/30", "Humulin 70/30", "Humulin 70/30 70/30", "Humulin 70/30 KwikPen", "Humulin L", "Humulin N", "Humulin N", "Humulin N", "Humulin N", "Humulin N", "Humulin N", "Humulin N (cartridge)", "Humulin N (kwikpen)", "Humulin R", "Humulin R", "Humulin R", "Humulin R", "Humulin R", "Humulin R (kwikpen)", "Humulin R Cartridge", "Humulin R U-500", "Humulin R U-500 KwikPen", "Humulin U", "Inpremzia", "Insulatard", "Insulatard", "Insulatard", "Insulatard", "Insulatard", "Insulatard", "Insulatard Flexpen", "Insulatard Flexpen", "Insulatard Flexpen", "Insulatard Innolet", "Insulatard Innolet", "Insulatard Innolet", "Insulatard Penfill", "Insulatard Penfill", "Insulatard Penfill", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Basal", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 15", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 25", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 30", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Comb 50", "Insulin Human Winthrop Infusat", "Insulin Human Winthrop Infusat", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insulin Human Winthrop Rapid", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Basal", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 15", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 25", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 30", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Comb 50", "Insuman Implantable", "Insuman Implantable", "Insuman Infusat", "Insuman Infusat", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Insuman Rapid", "Lente Purified Pork Insulin Inj", "Mixtard 30", "Mixtard 30", "Mixtard 30", "Mixtard 30", "Mixtard 30", "Mixtard 30", "Mixtard 30 Flexpen", "Mixtard 30 Flexpen", "Mixtard 30 Flexpen", "Mixtard 30 Innolet", "Mixtard 30 Innolet", "Mixtard 30 Innolet", "Mixtard 30 Penfill", "Mixtard 30 Penfill", "Mixtard 30 Penfill", "Mixtard 40 Penfill", "Mixtard 40 Penfill", "Mixtard 40 Penfill", "Mixtard 50 Penfill", "Mixtard 50 Penfill", "Mixtard 50 Penfill", "Myxredlin", "Myxredlin", "Novolin 70/30", "Novolin 70/30", "Novolin 70/30", "Novolin 70/30", "Novolin 70/30", "Novolin 70/30", "Novolin 70/30", "Novolin 70/30", "Novolin 70/30", "Novolin 70/30", "Novolin Ge 10/90 Penfill Inj Sus", "Novolin Ge 10/90 Penfill Inj Sus", "Novolin Ge 20/80 Penfill Inj Sus", "Novolin Ge 20/80 Penfill Inj Sus", "Novolin Ge 30/70", "Novolin Ge 30/70", "Novolin Ge 30/70 Penfill", "Novolin Ge 30/70 Penfill", "Novolin Ge 40/60 Penfill", "Novolin Ge 40/60 Penfill", "Novolin Ge 50/50 Penfill", "Novolin Ge 50/50 Penfill", "Novolin Ge Nph", "Novolin Ge Nph Penfill", "Novolin Ge Toronto", "Novolin Ge Toronto Penfill", "Novolin N", "Novolin N", "Novolin N", "Novolin N", "Novolin N", "Novolin N", "Novolin N", "Novolin N", "Novolin N", "Novolin R", "Novolin R", "Novolin R", "Novolin R", "Novolin R", "Novolin R", "Novolin R", "Novolin R", "Novolin R", "Novolin70/30 70/30", "NovolinN N", "Novolinset Ge 30/70 Inj Sus", "Novolinset Ge 30/70 Inj Sus", "Novolinset Ge Nph Inj Sus 100u/ml", "Novolinset Ge Toronto Inj Liq 100u/ml", "Protaphane", "Protaphane", "Protaphane", "Protaphane", "Protaphane", "Protaphane", "Protaphane Flexpen", "Protaphane Flexpen", "Protaphane Flexpen", "Protaphane Innolet", "Protaphane Innolet", "Protaphane Innolet", "Protaphane Penfill", "Protaphane Penfill", "Protaphane Penfill", "Velosulin", "Velosulin", "Velosulin" ]

[]

[ "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Exubera", "Exubera", "Novolin Ge 40/60 Penfill", "Novolin Ge 40/60 Penfill", "Novolin Ge 30/70 Penfill", "Novolin Ge 30/70 Penfill", "Novolin Ge 30/70", "Novolin Ge 30/70", "Novolin Ge 50/50 Penfill", "Novolin Ge 50/50 Penfill", "Humulin 10/90 Inj", "Humulin 10/90 Inj", "Humulin 10/90 Cartridge", "Humulin 10/90 Cartridge", "Humulin 20/80 Inj", "Humulin 20/80 Inj", "Humulin 20/80 Cartridge", "Humulin 20/80 Cartridge", "Humulin 40/60 Inj", "Humulin 40/60 Inj", "Humulin 40/60 Cartridge", "Humulin 40/60 Cartridge", "Humulin 50/50 Inj", "Humulin 50/50 Inj", "Humulin 50/50 Cartridge", "Humulin 50/50 Cartridge", "Novolin Ge 20/80 Penfill Inj Sus", "Novolin Ge 20/80 Penfill Inj Sus", "Novolin Ge 10/90 Penfill Inj Sus", "Novolin Ge 10/90 Penfill Inj Sus", "Novolinset Ge 30/70 Inj Sus", "Novolinset Ge 30/70 Inj Sus", "Humulin 30/70 Cartridge", "Humulin 30/70 Cartridge", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Afrezza", "Humulin 30/70 (insulin Human Biosynth Inj)", "Humulin 30/70 (insulin Human Biosynth Inj)" ]

[ "P06213", "P08069", "P16870", "P48745", "P98164", "Q16270" ]

[ "P14735", "P16519", "P29120", "P05177" ]

[]

DB00031

Tenecteplase

Tenecteplase is a tissue plasminogen activator (tPA) developed from modifications of natural human tPA complementary DNA (cDNA). It is a 527 amino acid with a substitution of threonine 103 with asparagine and substitution of asparagine 117 with glutamine within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296-299 in the protease domain.

liquid

For treatment of myocardial infarction and lysis of intracoronary emboli

Tenecteplase is a fibrin-specific tissue-plasminogen activator. It binds to fibrin rich clots and cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action. This helps eliminate blood clots or arterial blockages that cause myocardial infarction.

Tenecteplase binds to fibrin rich clots via the fibronectin finger-like domain and the Kringle 2 domain. The protease domain then cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.

null

1.9 hours (mammalian reticulocytes, in vitro) >20 hours (yeast, in vivo) >10 hours (Escherichia coli, in vivo)

null

* 99 - 119 mL/min [acute myocardial infarction patients]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "B01AD", "B01A", "B01", "B" ]

[ "Humans and other mammals" ]

[ { "cost": "3238.76", "description": "Tnkase 50 mg kit", "unit": "kit" } ]

[ { "approved": "2005-06-28", "country": "Canada", "expires": "2013-05-28", "number": "2129660" }, { "approved": "2003-06-17", "country": "Canada", "expires": "2020-06-17", "number": "1341432" } ]

Tenecteplasa | Tenecteplase | TNK-tPA | 3.4.21.7

[ "Metalyse", "Metalyse", "Metalyse", "TNKase", "TNKase", "TNKase", "TNKase" ]

[]

[ "TNKase" ]

[ "P00747" ]

[]

DB00032

Menotropins

Menotropins contains follicle stimulating hormone (FSH) and luteinizing hormone (LH) purified from the urine of postmenopausal women. It is used as a fertility medication that is injected either subcutaneously or intramuscularly. It is composed of LH with 2 subunits, alpha = 92 residues, beta = 121 residues and FSH with 2 subunits, alpha = 92 residues, beta=111 residues.

liquid

For the treatment of female infertility

Used to treat female infertility, Menotropins stimulates late follicular maturation and resumption of oocyte meiosis, and initiates rupture of the pre-ovulatory ovarian follicle. Menotropins bind to the LH/hCG/FSH receptor of the granulosa and theca cells of the ovary to effect these changes in the absence of an endogenous LH surge.

Being a combination drug, Menotropins bind to the follicle stimulating hormone receptor (FSH), which results in ovulation in the absence of sufficient endogenous luteinizing hormone (LH). It also binds the LH receptor, thereby stimulating proper hormone release. The drug contains both FSH and LH, therefore, it induces ovarian follicular growth and development as well as gonadal steroid production in women who do not have ovarian failure. FSH is the primary driver of follicular recruitment and growth in early folliculogenesis, while LH is important for ovarian steroidogenesis and is involved in the physiological events leading to development of a competent pre-ovulatory follicle.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "G03GA", "G03G", "G03", "G", "G03GA", "G03G", "G03", "G" ]

[ "Humans and other mammals" ]

[ { "cost": "93.85", "description": "Menopur 75 unit vial", "unit": "vial" }, { "cost": "93.85", "description": "Repronex 75 unit vial", "unit": "vial" }, { "cost": "488.04", "description": "Repronex 5 75 unit Solution 1 Box Contains Five 1ml Vials", "unit": "box" } ]

[]

[ "Menopur", "Repronex" ]

[]

[ "P23945", "P22888" ]

[]

DB00033

Interferon gamma-1b

Human Interferon gamma-1b (140 residues), produced from E. coli. Production of Actimmune is achieved by fermentation of a genetically engineered Escherichia coli bacterium containing the DNA which encodes for the human protein. Purification of the product is achieved by conventional column chromatography. The sequence displayed is a cDNA sequence which codes for human interferon gamma, as described by Gray et. al. and not specifically interferon gamma 1b.

liquid

Interferon gamma-1b is used for the treatment of Chronic granulomatous disease and Osteopetrosis.

IFN gamma stimulates expression of the immunoglobulin heavy chain C gamma 3 and C gamma 2a germline transcripts in B cells. Many components of the antigen presentation pathways are also up-regulated by interferon gamma. It is also a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of type I interferons. Interferon gamma may also help the body regulate the activity of fibroblasts. By directly blocking the multiplication of fibroblasts and inhibiting the production and action of TGF-b, a potent scar-inducing molecule, Interferon gamma-1b may prevent excessive scarring.

Binds directly to the type II interferon gamma receptor IFNGR1, leading to a complex of IFNGR1 and IFNGR2. This activates JAK1 and JAK2 kinases which form a STAT1 docking site. This leads to STAT1 phosphorylation, nuclear translocation and initiation of gene transcription of multiple immune-related genes.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[]

[ { "cost": "344.4", "description": "Actimmune 2 million unit vial", "unit": "vial" } ]

[ { "approved": "2005-08-30", "country": "United States", "expires": "2022-08-30", "number": "6936695" }, { "approved": "2005-08-30", "country": "United States", "expires": "2022-08-30", "number": "6936694" } ]

[ "Actimmune", "Actimmune", "Actimmune" ]

[ "Immukin" ]

[]

[ "P15260", "P38484" ]

[ "P05177" ]

[]

DB00034

Interferon alfa-2a

Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences.

liquid

For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection.

Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R.

Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta.

Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously.

null

Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair.

The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours).

null

Alpha-interferons are totally filtered through the glomeruli and undergo rapid proteolytic degradation during tubular reabsorption, rendering a negligible reappearance of intact alfa interferon in the systemic circulation.

* 0.223 to 0.748 L/kg [healthy people]

* 2.14 - 3.62 mL/min/kg [healthy]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L03AB", "L03A", "L03", "L" ]

[ "Humans and other mammals" ]

[]

[ { "approved": "2000-10-03", "country": "Canada", "expires": "2016-03-26", "number": "2172664" } ]

[ "Roferon A Soln Inj 6 Million", "Roferon A Sterile Pws 18m Unit/vial", "Roferon A Sterile Pws 3m Unit/vial", "Roferon A Sterile Pws 9m Unit/vial", "Roferon-A", "Roferon-A", "Roferon-A", "Roferon-A Sol Inj 3million Iu/vial", "Roferon-A Soln-liq Im Sc 4.5million I.u/ml", "Roferon-A Soln-liq Im Sc 9million I.U./ml", "Roferon-A Solution 18 Million I.U./3ml", "Roferon-A Solution 3 Million I.U./ml", "Roferon-A Solution 6 Million I.U./ml", "Roferon-A Solution Inj 36000000unit/ml", "Roferon-A Solution Inj. 9million I.U./0.9ml" ]

[ "Roferon A", "Veldona" ]

[]

[ "P17181", "P48551" ]

[ "P05177" ]

[]

DB00035

Desmopressin

Desmopressin (dDAVP), a synthetic analogue of 8-arginine vasopressin (ADH), is an antidiuretic peptide drug modified by deamination of 1-cysteine and substitution of 8-L-arginine by 8-D-arginine. ADH is an endogenous pituitary hormone that has a crucial role in the control of the water content in the body. Upon release from the stimulation of increased plasma osmolarity or decreased circulating blood volume, ADH mainly acts on the cells of the distal part of the nephron and the collecting tubules in the kidney [T28]. The hormone interacts with V1, V2 or V3 receptors with differing signal cascade systems. Desmopressin displays enhanced antidiuretic potency, fewer pressor effects due to V2-selective actions, and a prolonged half-life and duration of action compared to endogenous ADH [A31661]. It has been employed clinically since 1972 and is available in various formulations including intranasal solution, intravenous solution, oral tablet and oral lyophilisate [A31662]. Desmopressin is indicated for the treatment of polyuric conditions including primary nocturnal enuresis, nocturia, and diabetes insipidus. It was also newly approved for the treatment of mild classical hemophilia and von Willebrand's disease for minor surgeries. The active ingredient in most formulations is desmopressin acetate. Nocdurna, or desmopressin acetate, was approved by the FDA on June 21st, 2018 for the treatment of nocturia due to nocturnal polyuria in adults. It is available as a sublingual tablet.

solid

- Indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void (intranasal). - Indicated as antidiuretic replacement therapy in the management of central cranial diabetes insipidus and for management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region (intranasal/parenteral). - Indicated for patients with hemophilia A with factor VIII coagulant activity levels greater than 5% or mild to moderate classic von Willebrand's Disease (Type I) with factor VIII levels greater than 5% during surgical procedures and postoperatively to maintain hemostasis (parenteral).

By mimicking the actions of endogenous ADH, desmopressin acts as a selective agonist of V2 receptors expressed in the renal collecting duct (CD) to increase water re-absorption and reduce urine production. Desmopressin has been shown to be more potent than ADH in increasing plasma levels of factor VIII activity in patients with hemophilia and von Willebrand's disease Type I [L1183]. Desmopressin demonstrates markedly diminished pressor activity. Desmopressin administered intranasally has an antidiuretic effect about one-tenth that of an equivalent dose administered by injection [L1182].

Upon binding of desmopressin to V2 receptors in the basolateral membrane of the cells of the distal tubule and collecting ducts of the nephron, adenylyl cyclase is stimulated. The resulting intracellular cascades in the collecting duct lead to increased rate of insertion of water channels, called aquaporins, into the lumenal membrane and enhanced the permeability of the membrane to water [T28].

Following nasal spray administration of 0.83 mcg and 1.66 mcg, median time to peak plasma concentrations (Tmax) was 0.25 and 0.75 hour, respectively [FDA Label]. The peak plasma concentration was approximately 4.00 (± 3.85) pg/mL and 9.11 (± 6.90) pg/mL, respectively [FDA Label]. The bioavailability of 1.5 mg/mL desmopressin administered by the intranasal route was between 3.3 and 4.1% [L1183]. The absolute bioavailability of orally administered desmopressin varies between 0.08% and 0.16% where the mean maximum plasma concentration is reached within 2 hours [L1184].

In vitro, in human liver microsome preparations, it has been shown that no significant amount of desmopressin is metabolised in the liver and thus human liver metabolism in vivo is not likely to occur [L1184].

Intravenous TDLo in humans is reported to be 0.3 µg/kg/10M [MSDS]. Desmopressin is associated with hyponatremia in case of overdose, which may require temporary or permanent discontinuation of the therapy depending on severity. The effects of hyponatremia include seizure, altered mental status (confusion, drowsiness or continuing headache), cardiac arrhythmias and worsening edema. Other signs of overdose may include oliguria and rapid weight gain due to fluid retention [FDA Label]. In case of overdose, reduce the dose or frequency of drug administration, or discontinue use if appropriate. Assessment of serum sodium and initiation of appropriate medical treatment is recommended.

Following an intranasal dose of 1.66 mcg of desmopressin, the median apparent terminal half-life was 2.8 hours [FDA Label]. Terminal half-life significantly increased from 3 hours in normal healthy patients to 9 hours in patients with severe renal impairment [FDA Label]. The oral terminal half life of desmopressin ranges from 2 to 3.11 hours [L1184].

Following radioiodination (125I) in the N-terminal, the fraction of plasma protein binding of desmopressin was reported to be 17.3 ± 1.5% in a pharmacokinetic study involving healthy subjects [A31736].

Desmopressin is mainly excreted in the urine. About 65% of the amount of desmopressin absorbed after oral administration could be recovered in the urine within 24 hours [L1184].

The distribution volume of orally administered desmopressin is 0.2 – 0.32 l/kg [L1184]. It is not reported to cross the blood-brain barrier.

null

[ "approved" ]

[ "H01BA", "H01B", "H01", "H" ]

[ "Humans and other mammals" ]

[ { "cost": "1.48", "description": "Apo-Desmopressin 10 mcg/dose Metered Dose Spray", "unit": "dose" }, { "cost": "1.49", "description": "Ddavp 0.1 mg Tablet", "unit": "tablet" }, { "cost": "1.67", "description": "Apo-Desmopressin 0.2 mg Tablet", "unit": "tablet" }, { "cost": "1.67", "description": "Novo-Desmopressin 0.2 mg Tablet", "unit": "tablet" }, { "cost": "1.67", "description": "Pms-Desmopressin 0.2 mg Tablet", "unit": "tablet" }, { "cost": "2.13", "description": "Ddavp 10 mcg/dose Metered Dose Spray", "unit": "dose" }, { "cost": "2.98", "description": "Ddavp 0.2 mg Tablet", "unit": "tablet" }, { "cost": "3.08", "description": "Desmopressin acetate 0.1 mg tablet", "unit": "tablet" }, { "cost": "4.44", "description": "Desmopressin acetate 0.2 mg tablet", "unit": "tablet" }, { "cost": "4.47", "description": "Ddavp 0.1 mg tablet", "unit": "tablet" }, { "cost": "6.43", "description": "Ddavp 0.2 mg tablet", "unit": "tablet" }, { "cost": "7.08", "description": "Desmopressin ac 4 mcg/ml vial", "unit": "ml" }, { "cost": "7.28", "description": "Desmopressin ac 4 mcg/ml amp", "unit": "ml" }, { "cost": "11.33", "description": "Ddavp 4 mcg/ml", "unit": "ml" }, { "cost": "17.39", "description": "Octostim 150 mcg/dose Metered Dose Spray", "unit": "dose" }, { "cost": "21.26", "description": "Ddavp 0.1 mg/ml Solution", "unit": "ml" }, { "cost": "39.6", "description": "Desmopressin 0.1 mg/ml spray", "unit": "ml" }, { "cost": "43.27", "description": "Ddavp 4 mcg/ml ampul", "unit": "ml" }, { "cost": "50.76", "description": "Ddavp 0.01% nasal spray", "unit": "ml" }, { "cost": "334.2", "description": "Stimate 1.5 mg/ml nasal spray", "unit": "ml" }, { "cost": "0.83", "description": "Apo-Desmopressin 0.1 mg Tablet", "unit": "tablet" }, { "cost": "0.83", "description": "Novo-Desmopressin 0.1 mg Tablet", "unit": "tablet" }, { "cost": "0.83", "description": "Pms-Desmopressin 0.1 mg Tablet", "unit": "tablet" } ]

[ { "approved": "2006-04-04", "country": "United States", "expires": "2023-04-30", "number": "7022340" }, { "approved": "1996-03-19", "country": "United States", "expires": "2013-06-29", "number": "5500413" }, { "approved": "2007-01-16", "country": "Canada", "expires": "2023-05-07", "number": "2484724" }, { "approved": "2005-08-02", "country": "Canada", "expires": "2024-04-30", "number": "2486833" }, { "approved": "2017-01-10", "country": "United States", "expires": "2030-06-15", "number": "9539302" }, { "approved": "2010-09-21", "country": "United States", "expires": "2024-09-26", "number": "7799761" }, { "approved": "2008-07-29", "country": "United States", "expires": "2023-05-06", "number": "7405203" }, { "approved": "2009-08-25", "country": "United States", "expires": "2023-05-06", "number": "7579321" }, { "approved": "2018-03-20", "country": "United States", "expires": "2023-05-07", "number": "9919025" }, { "approved": "2015-12-29", "country": "United States", "expires": "2023-05-07", "number": "9220747" }, { "approved": "2016-11-29", "country": "United States", "expires": "2023-05-07", "number": "9504647" }, { "approved": "2018-05-22", "country": "United States", "expires": "2030-04-13", "number": "9974826" }, { "approved": "2014-08-12", "country": "United States", "expires": "2023-12-29", "number": "8802624" }, { "approved": "2009-07-14", "country": "United States", "expires": "2024-02-02", "number": "7560429" }, { "approved": "2011-05-24", "country": "United States", "expires": "2023-12-29", "number": "7947654" }, { "approved": "2018-11-27", "country": "United States", "expires": "2029-05-21", "number": "10137167" }, { "approved": "2019-06-04", "country": "United States", "expires": "2023-05-07", "number": "10307459" }, { "approved": "2021-06-01", "country": "United States", "expires": "2029-05-21", "number": "11020448" }, { "approved": "2010-06-15", "country": "United States", "expires": "2030-06-15", "number": "11419914" }, { "approved": "2009-05-21", "country": "United States", "expires": "2029-05-21", "number": "11963995" }, { "approved": "2010-06-15", "country": "United States", "expires": "2030-06-15", "number": "12090190" } ]

[ "Apo-desmopressin", "Apo-desmopressin", "Bipazen", "Ddavp", "Ddavp", "Ddavp", "Ddavp", "Ddavp", "Ddavp", "Ddavp", "Ddavp", "Ddavp", "Ddavp", "Ddavp", "Ddavp Inj 4mcg/ml", "Ddavp Melt", "Ddavp Melt", "Ddavp Melt", "DDAVP Rhinal Tube", "Ddavp Rhinyle", "Ddavp Spray", "Ddavp Tablets 0.1mg", "Ddavp Tablets 0.2mg", "Desmopressin", "Desmopressin", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin acetate", "Desmopressin acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin Acetate", "Desmopressin acetate", "Desmopressin acetate", "Desmopressin Spray", "Desmopressin Tablets", "Desmopressin Tablets", "Minirin", "Minirin", "Nocdurna", "Nocdurna", "Nocdurna", "Nocdurna", "Nocdurna", "Nocdurna", "Noctiva", "Noctiva", "Nu-desmopressin Spray", "Octostim Liq Inj. 15mcg/ml", "Octostim Spray", "PMS-desmopressin", "PMS-desmopressin", "Stimate", "Stimate", "Teva-desmopressin", "Teva-desmopressin" ]

[ "Adiuretin", "DesmoMelt" ]

[]

[ "P30559", "P30518", "P37288", "P47901" ]

[ "P35354", "P23219" ]

[]

DB00036

Coagulation factor VIIa Recombinant Human

Recombinant human coagulation Factor VIIa (rFVIIa), intended for promoting hemostasis by activating the extrinsic pathway of the coagulation cascade. NovoSeven is a vitamin K-dependent glycoprotein consisting of 406 amino acid residues. Cloned and expressed in hamster kidney cells, the protein is catalytically active in a two-chain form.

liquid

For treatment of hemorrhagic complications in hemophilia A and B.

Used in the treatment of bleeding episodes in hemophilia A or B. NovoSeven is recombinant Factor VIIa and, when complexed with tissue factor can activate coagulation Factor X to Factor Xa, as well as coagulation Factor IX to Factor IXa. Factor Xa, in complex with other factors, then converts prothrombin to thrombin, which leads to the formation of a hemostatic plug by converting fibrinogen to fibrin and thereby inducing local clotting.

NovoSeven activates the coagulation or clotting cascade by cleaving Factor IX and Factor X, which activates them and then leads to activation of thrombin and fibrin.

null

* 121 ± 30 mL/kg [adults] * 153 ± 29 mL/kg [children] * 280 to 290 mL/kg [congenital Factor VII deficiency]

* 33 - 37 mL/h x kg [healthy] * 1375 +/- 396 mL/hr [severe hemophilia A male children] * 57.3 +/- 9.5 mL/hr/kg [severe hemophilia A male children] * 2767 +/- 385 mL/hr [severe hemophilia A men] * 37.6 +/- 13.1 mL/hr/kg [severe hemophilia A men]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "B02BD", "B02B", "B02", "B" ]

[ "Humans and other mammals" ]

[ { "cost": "1.64", "description": "Novoseven 1200 mcg vial", "unit": "vial" }, { "cost": "1.64", "description": "Novoseven 2400 mcg vial", "unit": "vial" }, { "cost": "1.64", "description": "Novoseven 4800 mcg vial", "unit": "vial" } ]

[]

[ "Cevenfacta", "Cevenfacta", "Cevenfacta", "Niastase", "Niastase", "Niastase", "Niastase RT", "Niastase RT", "Niastase RT", "Niastase RT", "Niastase RT", "Niastase RT", "Niastase RT", "Niastase RT", "Novoseven", "Novoseven", "Novoseven", "Novoseven", "Novoseven", "Novoseven", "Novoseven", "Novoseven", "NovoSeven RT", "NovoSeven RT", "NovoSeven RT", "NovoSeven RT", "NovoSeven RT", "NovoSeven RT", "NovoSeven RT", "NovoSeven RT", "Sevenfact", "Sevenfact", "Sevenfact" ]

[]

[ "P00742", "P13726" ]

[]

DB00038

Oprelvekin

Oprelvekin, the active ingredient in Neumega®, is recombinant Interleukin-11 (IL-11), which is produced in Escherichia coli (E. coli) by recombinant DNA technology. With a molecular mass of approximately 19,000 daltons, the non-glycosylated protein is 177 amino acids in length in comparison to the natural IL-11, which is 178 amino acid long. However, it displays comparable biological activity compared to the natural IL-11 _in vitro_ and _in vivo_. Oprelvekin works by stimulating megakaryocytopoiesis and thrombopoiesis. In mice and nonhuman primate studies of animals with moderate and severe myelosuppression, in addition to compromised hematopoiesis, oprelvekin was shown to potently induce thrombopoiesis and improve platelet nadirs and accelerated platelet recoveries compared to controls. In animal studies, oprelvekin was also shown to regulate intestinal epithelium growth by enhancing healing of gastrointestinal lesions, inhibit adiopegenesis and macrophageal released pro-inflammatory cytokines, and induce acute phase protein synthesis.

liquid

Indicated for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in adult patients with nonmyeloid malignancies who are at high risk of severe thrombocytopenia.[Label]

Oprelvekin promotes hematopoiesis by stimulating megakaryocytopoiesis and thrombopoiesis. It is used in adult patients with nonmyeloid malignancies to prevent severe thrombocytopenia and reduce the need for platelet transfusions following therapies that cause myelosuppression. Its use is prioritized in patients who are at an elevated risk for developing severe thrombocytopenia. In clinical trials, oprelvekin has shown potent thrombopoietic activity in individuals with compromised hematopoiesis.

Oprelvekin binds to the interleukin 11 receptor which leads to a cascade of signal transduction events. Its pharmacological action mimics the biological activity of endogenous IL-11, which is a thrombopoietic growth factor that directly stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induces megakaryocyte maturation resulting in increased platelet production.

Absolute bioavailability is over 80%.

null

6.9 +/- 1.7 hrs

null

The kidney is the primary route of elimination. The amount of intact Neumega in urine was low, indicating that the molecule was metabolized before excretion.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L03AC", "L03A", "L03", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "352.9", "description": "Neumega 5 mg vial", "unit": "vial" } ]

[]

[ "Neumega" ]

[]

[ "Q14626" ]

[]

DB00039

Palifermin

Palifermin is a recombinant human keratinocyte growth factor (KGF). It is 140 residues long, and is produced using E. coli. Palifermin was granted FDA approval on 15 December 2004.[L17933]

liquid

For treatment of oral mucositis associated with chemotherapy and radiation therapy.

Used in the prevention or treatment of oral mucoscitis (mouth ulcers arising from chemotherapy), Kepivance binds to the human keratinocyte growth factor (KGF) receptor on buccal cell surfaces. Kepivance acts as both a cell growth and survival factor by stimulating epithelial cell proliferation, differentiation, and migration around the tongue and mouth. The KGF receptor is found on many tissues particularly around the tongue, esophagus, salivary gland and other gastro-intestinal tract organs.

Palifermin has been shown to protect oral and intestinal epithelia from the effects of radiation and chemotherapy, though the exact mechanism is not well understood.[A222248] As a recombinant keratinocyte growth factor (KGF), palifermin may promote cell proliferation, reducing the severity of oral mucositis in patients in the relevant treatment groups.[A222248] Agonism of fibroblast growth factor 2 may be predominantly responsible for this effect.[A52198] The endogenous form if palifermin is expressed in the kidney of rats.[A13175]

null

Elimination half-life: 4.5 hours (range: 3.3-5.7 hours)

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "V03AF", "V03A", "V03", "V" ]

[ "Humans and other mammals" ]

[ { "cost": "1650.0", "description": "Kepivance 6.25 mg vial", "unit": "vial" } ]

[]

[ "Kepivance", "Kepivance", "Kepivance", "Kepivance" ]

[]

[ "P21802", "P11362", "P98160" ]

[]

DB00040

Glucagon

Glucagon is a 29 amino acid hormone used as a diagnostic aid in radiologic exams to temporarily inhibit the movement of the gastrointestinal tract and to treat severe hypoglycemia.[L7634,L7637,L7640,L7643,L8519] Glucagon raises blood sugar through activation of hepatic glucagon receptors, stimulating glycogenolysis and the release of glucose.[L7640,L7643] Glucagon was granted FDA approval on 14 November 1960.[L7631]

liquid

Glucagon is indicated as a diagnostic aid in radiologic exams to temporarily inhibit the movement of the gastrointestinal tract and to treat severe hypoglycemia.[L7634,L7637,L7640,L7643,L8519]

Glucagon is indicated as a diagnostic aid in radiologic exams to temporarily inhibit the movement of the gastrointestinal tract and severe hypoglycemia.[A19402,L7634,L7637,L7640,L7643,L8519] Glucagon raises blood sugar through activation of hepatic glucagon receptors, stimulating glycogenolysis and the release of glucose.[L7640,L7643] Glucagon has a short duration of action.[L7634,L7637,L7640,L7643] Glucagon may cause hyperglycemia in diabetic patients.[L7634,L7637,L7640,L7643]

Glucagon binds to the glucagon receptor activating Gsα and Gq.[A19402] This activation activates adenylate cyclase, which increases intracellular cyclic AMP and activates protein kinase A.[A19402] Activating Gq activates phospholipase C, increases production of inositol 1,4,5-triphosphate, and releases intracellular calcium.[A19402] Protein kinase A phosphorylates glycogen phosphorylase kinase, which phosphorylates glycogen phosphorylase, which phosphorylates glycogen, causing its breakdown.[A19402] Glucagon also relaxes smooth muscle of the stomach, duodenum, small bowel, and colon.[L7634,L7643]

A 1mg intravenous dose of glucagon reaches a Cmax of 7.9ng/mL with a Tmax of 20 minutes.[L7637] An intramuscular dose reaches a Cmax of 6.9ng/mL with a Tmax of 13 minutes.[L7637] A 3mg dose of glucagon nasal powder reaches a Cmax of 6130pg/mL with a Tmax of 15 minutes.[L7643]

Glucagon is a protein and so it is metabolized into smaller polypeptides and amino acids in the liver, kidney, and plasma.[L7634,L7643]

Patients experiencing an overdose may present with nausea, vomiting, inhibition of GI tract motility, increased blood pressure and heart rate, and decreased serum potassium.[L7634,L7637,L7640,L7643] Phentolamine may be given to control blood pressure.[L7634,L7637,L7640,L7643] Treatment of glucagon overdose is largely symptomatic for nausea, vomiting, and hypokalemia.[L7637] The LD50 for intravenous glucagon in mice is 300mg/kg and in rats is 38.6mg/kg.[L7637]

The half life of glucagon is 26 minutes for an intramuscular dose.[L7634] The half life of glucagon nasal powder is approximately 35 minutes.[L7643] The half life of glucagon by a subcutaneous auto-injector or pre-filled syringe is 32 minutes.[L8519]

Glucagon has not been described in the literature as bound to a protein in serum.[A181649,A181667,L7634,L7637,L7640,L7643,L7658]

Elimination of glucagon is not fully characterized in literature, however the kidney and liver appear to contribute significantly in animal models.[A181649] The liver and kidney are responsible for approximately 30% of glucagon elimination each.[L7658]

The volume of distribution of glucagon is 0.25L/kg.[L7637] The apparent volume of distribution is 885L.[L7643]

A 1mg intravenous dose of glucagon has a clearance of 13.5mL/min/kg.[L7637]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "H04AA", "H04A", "H04", "H" ]

[ "Humans and other mammals" ]

[ { "cost": "84.0", "description": "Glucagen 1 mg vial", "unit": "vial" }, { "cost": "94.98", "description": "Glucagon 1 mg/vial", "unit": "vial" }, { "cost": "119.28", "description": "Glucagon 1 mg emergency kit", "unit": "kit" }, { "cost": "120.36", "description": "Glucagen 1 mg hypokit", "unit": "kit" }, { "cost": "123.72", "description": "GlucaGen HypoKit 1 mg Solution Box", "unit": "box" }, { "cost": "124.05", "description": "Glucagon Emergency 1 mg Kit Box", "unit": "box" }, { "cost": "128.34", "description": "Glucagon 1 mg kit", "unit": "kit" } ]

[ { "approved": "2019-02-26", "country": "United States", "expires": "2036-02-16", "number": "10213487" }, { "approved": "2005-09-06", "country": "United States", "expires": "2022-01-03", "number": "6938798" }, { "approved": "2017-05-16", "country": "United States", "expires": "2036-04-22", "number": "9649364" }, { "approved": "2020-09-08", "country": "United States", "expires": "2039-09-23", "number": "10765602" }, { "approved": "2021-01-19", "country": "United States", "expires": "2038-01-03", "number": "10894133" }, { "approved": "2016-04-22", "country": "United States", "expires": "2036-04-22", "number": "11590205" } ]

[ "Baqsimi", "Baqsimi", "Baqsimi", "Baqsimi", "Baqsimi", "Baqsimi", "Glucag0n", "GlucaGen", "GlucaGen", "GlucaGen", "GlucaGen", "GlucaGen HypoKit", "GlucaGen HypoKit", "Glucagon", "Glucagon", "Glucagon", "Glucagon", "Glucagon", "Glucagon", "Glucagon", "Glucagon", "Glucagon", "Glucagon", "Glucagon", "Glucagon", "Glucagon Ampoule 666 1mg", "Gvoke HypoPen 0.5 mg Auto-Injector", "Gvoke HypoPen 1 mg Auto-Injector", "Gvoke Kit", "Gvoke Kit Vial", "Gvoke PFS 0.5 mg Pre-filled Syringe", "Gvoke PFS 1 mg Pre-filled Syringe", "Ogluo", "Ogluo", "Ogluo", "Ogluo", "Ogluo", "Ogluo", "Ogluo", "Ogluo" ]

[]

[ "Glucagon", "Glucagon", "Glucagon", "Glucagon" ]

[ "P47871", "O95838", "P43220" ]

[]

DB00041

Aldesleukin

Aldesleukin, a lymphokine, is produced by recombinant DNA technology using a genetically engineered E. coli strain containing an analog of the human interleukin-2 gene. Genetic engineering techniques were used to modify the human IL-2 gene, and the resulting expression clone encodes a modified human interleukin-2. This recombinant form differs from native interleukin-2 in the following ways: a) Aldesleukin is not glycosylated because it is derived from E. coli; b) the molecule has no N-terminal alanine; the codon for this amino acid was deleted during the genetic engineering procedure; c) the molecule has serine substituted for cysteine at amino acid position 125.

liquid

For treatment of adults with metastatic renal cell carcinoma.

Used to treat renal cell carcinoma, Aldesleukin induces the enhancement of lymphocyte mitogenesis and stimulation of long-term growth of human interleukin-2 dependent cell lines, the enhancement of lymphocyte cytotoxicity, the induction of killer cell (lymphokine-activated (LAK) and natural (NK)) activity; and the induction of interferon-gamma production. IL-2 is normally produced by the body, secreted by T cells, and stimulates growth and differentiation of T cell response. It can be used in immunotherapy to treat cancer. It enhances the ability of the immune system to kill tumor cells and may interfere with blood flow to the tumor.

Aldesleukin binds to the IL-2 receptor which leads to heterodimerization of the cytoplasmic domains of the IL-2R beta and gamma(c) chains, activation of the tyrosine kinase Jak3, and phosphorylation of tyrosine residues on the IL-2R beta chain. These events led to the creation of an activated receptor complex, to which various cytoplasmic signaling molecules are recruited and become substrates for regulatory enzymes (especially tyrosine kinases) that are associated with the receptor. These events stimulate growth and differentiation of T cells.

null

13 min-85 min

null

The pharmacokinetic profile of Proleukin is characterized by high plasma concentrations following a short IV infusion, rapid distribution into the extravascular space and elimination from the body by metabolism in the kidneys with little or no bioactive protein excreted in the urine. Following the initial rapid organ distribution, the primary route of clearance of circulating proleukin is the kidney. Greater than 80% of the amount of Proleukin distributed to plasma, cleared from the circulation and presented to the kidney is metabolized to amino acids in the cells lining the proximal convoluted tubules.

0.18 l/kg

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "L03AC", "L03A", "L03", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "976.66", "description": "Proleukin 22000000 unit Solution Vial", "unit": "vial" }, { "cost": "1092.34", "description": "Proleukin 22 million unit vial", "unit": "each" } ]

[]

[ "Proleukin", "Proleukin", "Proleukin", "Proleukin", "Proleukin", "Proleukin" ]

[]

[ "P14784", "P01589", "P31785" ]

[ "P35354", "P47712", "P08684", "P47989", "P05181" ]

[]

DB00042

Botulinum toxin type B

Neurotoxin produced by fermentation of clostridium botulinum type B. The protein exists in noncovalent association with hemagglutinin and nonhemagglutinin proteins as a neurotoxin complex. The neurotoxin complex is recovered from the fermentation process and purified through a series of precipitation and chromatography steps.

liquid

For the treatment of patients with cervical dystonia to reduce the severity of abnormal head position and neck pain associated with cervical dystonia.

Botulinum Toxin Type B inhibits acetylcholine release at the neuromuscular junction via a three stage process: 1) Heavy Chain mediated neurospecific binding of the toxin, 2) internalization of the toxin by receptor-mediated endocytosis, and 3) ATP and pH dependent translocation of the Light Chain to the neuronal cytosol where it acts as a zinc-dependent endoprotease cleaving polypeptides essential for neurotransmitter release.

Botulinum Toxin Type B binds to and cleaves the synaptic Vesicle Associated Membrane Protein (VAMP, also known as synaptobrevin) which is a component of the protein complex responsible for docking and fusion of the synaptic vesicle to the presynaptic membrane, a necessary step to neurotransmitter release.

Though pharmacokinetic or ADME studies were not performed, Botulinum Toxin Type B is not expected to be present in the peripheral blood at measurable levels following IM injection at the recommended doses.

null

One unit of Botulinum Toxin Type B corresponds to the calculated median lethal intraperitoneal dose (LD50) in mice.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "M03AX", "M03A", "M03", "M" ]

[ "Humans and other mammals" ]

[ { "cost": "299.4", "description": "Myobloc 2500 unit/0.5 ml vial", "unit": "vial" }, { "cost": "1245.5", "description": "Myobloc 10000 unit/2ml Solution 2ml Vial", "unit": "vial" } ]

[]

[ "Myobloc", "Myobloc", "Myobloc", "Myobloc", "Neurobloc", "Neurobloc", "Neurobloc", "Neurobloc" ]

[ "Neurobloc" ]

[]

[ "P63027", "P23763", "Q8N9I0" ]

[]

DB00043

Omalizumab

Omalizumab is a recombinant DNA-derived humanized monoclonal antibody directed against human immunoglobulin E (IgE).[L50482] IgE promotes the release of inflammatory mediators from mast cells and basophils during allergic and inflammatory reactions. By binding to IgE and neutralizing it, omalizumab reduces free IgE levels and prevents IgE from binding to its receptors on immune cells.[A39518] Omalizumab was first approved in the US in 2003 [A263507] and in Europe in 2005.[L50482] It is used to treat a range of immune and inflammatory conditions, including allergies, urticaria, and asthma.[A263507]

liquid

Omalizumab is indicated for: - the treatment of patients six years of age and older with moderate to severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids.[L50477, L50482] - add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adults with inadequate response to nasal corticosteroids.[L50477, L50482] - the reduction of allergic reactions (Type I), including anaphylaxis, that may occur with accidental exposure to one or more foods in patients aged one year and older with IgE-mediated food allergy. Omalizumab is to be used in conjunction with food allergen avoidance.[L50477] - the treatment of adults and adolescents 12 years of age and older with chronic spontaneous urticaria (CSU) who remain symptomatic despite H1 antihistamine treatment.[L50477]

Omalizumab decreases free IgE levels in serum in a dose-dependent manner. Serum total IgE levels, accounting for bound and unbound IgE, increased after the first dose of omalizumab due to the formation of drug:IgE complexes, which have a slower elimination rate compared with free IgE. At 16 weeks after the first dose, average total IgE levels in serum were five-fold higher compared to pre-treatment levels in standard assays. Drug effects on IgE levels are reversible upon drug discontinuation, with no observed rebound in IgE levels after drug washout. Total IgE levels did not return to pre-treatment levels for up to one year after discontinuation of omalizumab.[L50477]

IgE antibodies have been implicated in several immune-mediated diseases, including allergic hypersensitivity reactions and asthma. IgE binds to the high-affinity IgE receptor Fc-epsilon-RI typically found on inflammatory cells such as eosinophils, mast cells, and basophils.[A39518, A263507] IgE binding to Fc-epsilon-RI initiates a downstream cascade that releases pro-inflammatory mediators.[A39518] Omalizumab is an IgE-neutralizing antibody: It selectively binds to the C-epsilon-3 locus of IgE, the domain at which IgE binds to Fc-epsilon-RI to mediate its actions. Omalizumab works to lower circulating free IgE levels and prevent IgE from interacting with Fc-epsilon-RI,[A263507] which can also lead to the reduced expression of Fc-epsilon-RI.[A263532]

After subcutaneous administration, omalizumab has an average absolute bioavailability of 62%. In adult and adolescent patients with asthma, omalizumab was absorbed slowly and the peak serum concentrations occurred after seven to eight days.[L50477] The pharmacokinetics of omalizumab were linear at doses which were higher than 0.5 mg/kg. In patients with asthma, after several doses of omalizumab, areas under the serum concentration-time curve from Day 0 to Day 14 at steady state were up to 6-fold of those after one dose. After repeated dosing from 75mg-300 mg every 4 weeks, trough serum concentrations of omalizumab increased proportionally with the dose.[L50477]

Omalizumab is degraded in the reticuloendothelial system and endothelial cells.[A263507]

The intravenous LD50 in monkeys is 200 mg/kg.[L50487] Maximum tolerated dose of omalizumab has not been determined. Single intravenous doses up to 4000 mg have been administered to patients without evidence of dose-limiting toxicities. The highest cumulative dose administered to patients was 44,000 mg over a 20-week period and this dose did not result in any untoward acute effects. If an overdose is suspected, the patient should be monitored for any abnormal signs or symptoms. Medical treatment should be sought and instituted appropriately.[L50482]

In asthma patients, the serum elimination half-life averaged 26 days. In CSU patients, at steady state, based on population pharmacokinetics, omalizumab serum elimination half-life averaged 24 days.[L50477]

null

Liver elimination of IgG includes degradation in the liver reticuloendothelial system (RES) and endothelial cells. Intact IgG was also shown to be excreted in bile. In studies with mice and monkeys, omalizumab:IgE complexes were eliminated by interactions with Fc-gamma receptors within the RES at rates that were generally faster than IgG clearance.[L50477]

In patients with asthma, the apparent volume of distribution was 78 ± 32 mL/kg following subcutaneous administration.[L50477]

In pharmacokinetic studies, the clearance of omalizumab involved IgG clearance as well as clearance by specific binding and complex formation with its target ligand, IgE. The apparent clearance averaged 2.4 ± 1.1 mL/kg/day in patients with asthma. The apparent clearance averaged 240 mL/day (corresponding to 3.0 mL/kg/day for an 80 kg patient).[L50482]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "R03DX", "R03D", "R03", "R" ]

[ "Humans and other mammals" ]

[ { "cost": "715.42", "description": "Xolair 150 mg vial", "unit": "vial" } ]

[ { "approved": "2005-04-12", "country": "Canada", "expires": "2012-08-14", "number": "2113813" }, { "approved": "1998-12-15", "country": "Canada", "expires": "2015-12-15", "number": "1340233" } ]

Omalizumab | RHUMAB-E25 | Ig epsilon chain C region | Ig epsilon chain C region ND

[ "Omlyclo", "Omlyclo", "Omlyclo", "Omlyclo", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair", "Xolair PFS", "Xolair PFS" ]

[]

[ "P01854" ]

[]

DB00044

Lutropin alfa

Lutropin alfa is a recombinant human luteinizing hormone produced in yeast with 2 subunits, alpha = 92 residues, beta = 121 residues. It is a heterodimeric glycoprotein made up of monomeric units. Lutropin alfa was the first and only recombinant human form of luteinizing hormone (LH) developed for use in the stimulation of follicular development. Its pharmacological action mimics the biological activity of endogenous LH; an acute rise of LH, or LH surge, in females triggers ovulation and the development of the corpous luteum. In males, LH stimulates Leydig cell to produce testosterone.

liquid

For treatment of infertility in women with hypothalamic or pituitary insufficiency (hypogonadotropic hypogonadism) and profound LH deficiency (LH <1.2 international units [IU]/L)

Used to facilitate female conception, lutropin alfa performs the same actions as luteinizing hormone (LH), which is normally produced in the pituitary gland. Lutropin is usually given in combination with follitropin alfa. Together they stimulate the development of a follicle to prepare the reproductive tract for implementation and pregnancy. Lutropin alfa also stimulates the theca cells to produce androgens and the secretion of estradiol by the follicles. Lutropin alfa and follitropin alfa are discontinued once ultrasound assessment and serum estradiol concentrations show sufficient follicular maturation. hCG is then administered to complete follicular maturation and induce ovulation. In females, a LH surge about halfway through the menstrual cycle triggers the onset of ovulation. Lutropin alfa substitutes for endogenous LH and induces rupture of the preovulatory ovarian follicle and oocyte expulsion. Lutropin alfa induces and maintains the corpus luteum, which then secretes progesterone.

Luteinizing hormone binds to a receptor shared with the human chorionic gonadotropin hormone (hCG) on the ovarian theca (and granulosa) cells and testicular Leydig cells. This LH/CG transmembrane receptor is a member of the super-family of G protein-coupled receptors. Adenylate cyclase then activates many other pathways leading to steroid hormone production and other follicle maturation processes.

Mean absolute bioavailability is 56%, following sub-Q administration, maximum serum concentrations reached after 4–16 hours. Time to peak, serum: 9 hours

<5% of dose excreted renally as unchanged drug.

Lutropin alfa is not indicated for people under 16 and over 60, pregnant and lactating women, patients with uncontrolled thyroid and adrenal failure, patients with active, untreated tumours of the hypothalamus and pituitary gland, and in any patient with a condition that makes a normal pregnancy possible such as primary ovarian failure or fibroid tumors of the uterus.

Biphasic; terminal half-life is approximately 18 hours.

null

Total body clearance is approximately 2 to 3 L/h with less than 5 percent of the dose being excreted unchanged renally.

The steady state volume of distribution is around 10-14 L.

* 2 – 3 L/h [healthy female following subcutaneous administration]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "G03GA", "G03G", "G03", "G" ]

[ "Humans and other mammals" ]

[ { "cost": "38.88", "description": "Luveris 75 unit vial", "unit": "vial" } ]

[ { "approved": "1998-06-16", "country": "United States", "expires": "2015-06-16", "number": "5767251" } ]

[ "Luveris", "Luveris", "Luveris", "Luveris", "Luveris", "Luveris", "Luveris", "Luveris", "Luveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris" ]

[]

[ "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris" ]

[ "P22888" ]

[]

DB00045

Lyme disease vaccine (recombinant OspA)

Vaccine against Lyme disease that contains lipoprotein OspA, an outer surface protein of Borrelia burgdorferi sensu stricto ZS7, as expressed by Escherichia coli. Lipoprotein OspA is a single polypeptide chain of 257 amino acids with lipids covalently bonded to the N terminus. It is conjugated with alum (aluminum hydroxide) as an adjuvant.

liquid

For prophylactic treatment of Lyme Disease

OspA lipoprotein is a single polypeptide chain of 270 amino acids. It is a vaccination used to prevent Lyme Disease.

OspA lipoprotein, an outer surface protein of the bacteria Borrelia burgdorferi sensu stricto ZS7, is used to stimulate the production of specific antibodies against B. burgdorferi. It is used as a vaccination against Lyme Disease, a disease carried by ticks.

null

1.2 hours (mammalian reticulocytes, in vitro).

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "withdrawn" ]

[]

[ "Humans and other mammals" ]

[]

Lipoprotein OspA antigen recombinant | Lipoprotein outer surface a borrelia burgdorferi antigen | OspA lipoprotein | TIL4 | Toll/interleukin-1 receptor-like protein 4

[]

[ "LYMErix" ]

[]

[ "O60603" ]

[]

DB00046

Insulin lispro

Insulin lispro is a rapid-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Insulin is prescribed for the management of diabetes mellitus to mimic the activity of endogenously produced human insulin, a peptide hormone produced by beta cells of the pancreas that promotes glucose metabolism. Insulin is released from the pancreas following a meal to promote the uptake of glucose from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscle. Absorption of glucose into cells allows for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, enhances protein synthesis, and inhibits lipolysis and proteolysis among many other functions. Insulin is an important treatment in the management of Type 1 Diabetes (T1D) which is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting in the body not being able to produce the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin, such as insulin lispro, to lower glucose levels in the blood. Insulin is also used in the treatment of Type 2 Diabetes (T2D), another form of diabetes mellitus that is a slowly progressing metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Without treatment or improvement in non-pharmacological measures such as diet and exercise to lower blood glucose, high blood sugar eventually cause cellular resistance to endogenous insulin, and in the long term, damage to pancreatic islet cells. Insulin is typically prescribed later in the course of T2D, after several oral medications such as [DB00331], [DB01120], or [DB01261] have been tried, and when sufficient damage has been caused to pancreatic cells that the body is no longer able to produce insulin on its own. Marketed as the brand name product Humalog, insulin lispro begins to exert its effects within 15 minutes of subcutaneous administration, while peak levels occur 30 to 90 minutes after administration. Due to its duration of action of around 5 hours, Humalog is considered "bolus insulin" as it provides high levels of insulin in a short period of time to mimic the release of endogenous insulin from the pancreas after meals. Bolus insulin is often combined with once daily, long-acting "basal insulin" such as [DB01307], [DB09564], or [DB00047] to provide low concentrations of background insulin that can keep blood sugar stable between meals or overnight. Use of basal and bolus insulin together is intended to mimic the pancreas' production of endogenous insulin, with a goal of avoiding any periods of hypoglycemia. Insulin lispro is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli and was the first commercially available insulin analog. Formerly called LYSPRO from the chemical nomenclature [LYS(B28), PRO(B29)], insulin lispro differs from human insulin in that the amino acid proline at position B28 is replaced by lysine and the lysine in position B29 is replaced by proline. These biochemical changes result in a reduced tendency for self-association resulting in dissolution to a dimer and then to a monomer that is absorbed more rapidly after subcutaneous injection compared to endogenous human insulin. Without an adequate supply of insulin to promote absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high levels and can result in symptoms such as fatigue, headache, blurred vision, and increased thirst. If left untreated, the body starts to break down fat, instead of glucose, for energy which results in a build-up of ketone acids in the blood and a syndrome called ketoacidosis, which is a life-threatening medical emergency. In the long term, elevated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy.

liquid

Insulin lispro is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.[L47616]

Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin lispro is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin lispro is 10-15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 4-5 hours. Compared to regular human insulin, insulin lispro has a more rapid onset of action and a shorter duration of action. Insulin lispro is also shown to be equipotent to human insulin on a molar basis. Insulin lispro has been shown to be equipotent to human insulin on a molar basis. One unit of insulin lispro has the same glucose-lowering effect as one unit of regular human insulin. Studies in normal volunteers and patients with diabetes demonstrated that insulin lispro has a more rapid onset of action and a shorter duration of activity than regular human insulin when given subcutaneously.[L47616] The pharmacodynamics of a single 20 unit dose of insulin lispro at 200 units/mL (HUMALOG U-200) administered subcutaneously were compared to the pharmacodynamics of a single 20 unit dose of insulin lispro at 100 units/mL (HUMALOG U-100) administered subcutaneously in a euglycemic clamp study enrolling healthy subjects. In this study, the overall, maximum, and time to maximum glucose lowering effect were similar between HUMALOG U-200 and HUMALOG U-100. The mean area under the glucose infusion rate curves (measure of overall pharmacodynamic effect) were 125 g and 126 g for HUMALOG U-200 and HUMALOG U-100, respectively. The maximum glucose infusion rate was 534 mg/min and 559 mg/min and the corresponding median time (min, max) to maximum effect were 2.8 h (0.5 h – 6.3 h) and 2.4 h (0.5 h – 4.7 h) for HUMALOG U-200 and HUMALOG U-100, respectively.[L47616]

Insulin lispro binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Reversal of the proline and lysine residues at positions B28 and B29 of native insulin eliminates hydrophobic interactions and weakens some of the hydrogen bonds that contribute to the stability of the insulin dimers that comprise insulin hexamers. Hexamers of insulin lispro are produced in the presence of zinc and m-cresol. These weakly associated hexamers quickly dissociate upon subcutaneous injection and are absorbed as monomers through vascular endothelial cells. These properties give insulin lispro its fast-acting properties.

Studies in healthy volunteers and patients with diabetes demonstrated that insulin lispro is absorbed more quickly than regular human insulin, specifically at the abdominal, deltoid, or femoral subcutaneous sites. In healthy volunteers given subcutaneous doses of insulin lispro ranging from 0.1 to 0.4 unit/kg, peak serum levels were seen 30 to 90 minutes after dosing. When healthy volunteers received equivalent doses of regular human insulin, peak insulin levels occurred between 50 to 120 minutes after dosing. After insulin lispro was administered in the abdomen, serum drug levels were higher, and the duration of action was slightly shorter than after deltoid or thigh administration.[L47616] Bioavailability of insulin lispro is similar to that of regular human insulin. The absolute bioavailability after subcutaneous injection ranges from 55% to 77% with doses between 0.1 to 0.2 unit/kg, inclusive.[L47616] The mean observed area under the serum insulin concentration-time curve from time zero to infinity was 2360 pmol hr/L to 2390 pmol hr/L. The corresponding mean peak serum insulin concentration was 795 pmol/L to 909 pmol/L, and the median time to maximum concentration was 1.0 hour.[L47616]

Human metabolism studies have not been conducted. However, animal studies indicate that the metabolism of insulin lispro is identical to that of regular human insulin.[L47616]

Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. Rare cases of lipoatrophy or lipohypertrophy reactions have been observed. Excess insulin administration may cause hypoglycemia and hypokalemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with a glucagon product for emergency use or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.[L47616] Patients with renal or hepatic impairment may be at increased risk of hypoglycemia and may require more frequent insulin lispro dose adjustment and more frequent blood glucose monitoring.[L47616] Standard 2-year carcinogenicity studies in animals have not been performed. In Fischer 344 rats, a 12-month repeat-dose toxicity study was conducted with insulin lispro at subcutaneous doses of 20 and 200 units/kg/day (approximately 3 and 32 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area). Insulin lispro did not produce important target organ toxicity including mammary tumors at any dose.[L47616] Insulin lispro was not mutagenic in the following genetic toxicity assays: bacterial mutation, unscheduled DNA synthesis, mouse lymphoma, chromosomal aberration and micronucleus assays.[L47616] Male fertility was not compromised when male rats given subcutaneous insulin lispro injections of 5 and 20 units/kg/day (0.8 and 3 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area) for 6 months were mated with untreated female rats. In a combined fertility, perinatal, and postnatal study in male and female rats given 1, 5, and 20 units/kg/day subcutaneously (0.2, 0.8, and 3 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area), mating and fertility were not adversely affected in either gender at any dose.[L47616]

After subcutaneous administration of insulin lispro, the t1/2 is shorter than that of regular human insulin (1 versus 1.5 hours, respectively).[L47616] For intravenous administration, insulin lispro demonstrated a mean t1/2 of 0.85 hours (51 minutes) and 0.92 hours (55 minutes), respectively for 0.1 unit/kg and 0.2 unit/kg doses, and regular human insulin mean t1/2 was 0.79 hours (47 minutes) and 1.28 hours (77 minutes), respectively for 0.1 unit/kg and 0.2 unit/kg doses.[L47616]

null

When administered intravenously as bolus injections of 0.1 and 0.2 U/kg dose in two separate groups of healthy subjects, the mean volume of distribution of HUMALOG appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectively) in contrast to that of regular human insulin for which, the volume of distribution was comparable across the two dose groups (1.37 and 1.12 L/kg for 0.1 and 0.2 U/kg dose, respectively).[L47616]

When administered intravenously, insulin lispro and regular human insulin demonstrated similar dose-dependent clearance, with a mean clearance of 21.0 mL/min/kg and 21.4 mL/min/kg, respectively (0.1 unit/kg dose), and 9.6 mL/min/kg and 9.4 mL/min/kg, respectively (0.2 unit/kg dose).[L47616]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "A10AC", "A10A", "A10", "A", "A10AB", "A10A", "A10", "A", "A10AD", "A10A", "A10", "A" ]

[ "Humans and other mammals" ]

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[ "Admelog", "Admelog", "Admelog", "Admelog", "Admelog", "Admelog", "Admelog Solostar", "Humalog", "Humalog", "Humalog", "Humalog", "Humalog", "Humalog", "Humalog", "Humalog", "Humalog", "Humalog", "Humalog", "Humalog", "Humalog", "Humalog", "Humalog", "Humalog", "Humalog", "Humalog (cartridge)", "Humalog (kwikpen)", "Humalog 200 Units/ml Kwikpen", "Humalog Basal", "Humalog Basal", "Humalog Basal Kwikpen", "Humalog Basal Kwikpen", "Humalog Cartridge", "Humalog Junior KwikPen", "Humalog Junior Kwikpen", "Humalog Junior Kwikpen", "Humalog Junior Kwikpen", "Humalog KwikPen", "Humalog KwikPen", "Humalog KwikPen", "Humalog KwikPen", "Humalog KwikPen", "Humalog Kwikpen", "Humalog Kwikpen", "Humalog Kwikpen", "Humalog Kwikpen", "Humalog Kwikpen", "Humalog Kwikpen", "Humalog Mix 25 (cartridge)", "Humalog Mix 25 (cartridge)", "Humalog Mix 25 (kwikpen)", "Humalog Mix 25 (kwikpen)", "Humalog Mix 25 (pen)", "Humalog Mix 25 (pen)", "Humalog Mix 50 (cartridge)", "Humalog Mix 50 (cartridge)", "Humalog Mix 50 (kwikpen)", "Humalog Mix 50 (kwikpen)", "Humalog Mix25", "Humalog Mix25", "Humalog Mix25", "Humalog Mix25 Kwikpen", "Humalog Mix25 Kwikpen", "Humalog Mix50", "Humalog Mix50", "Humalog Mix50", "Humalog Mix50 Kwikpen", "Humalog Mix50 Kwikpen", "Humalog Mix50/50", "Humalog Mix50/50", "Humalog Mix50/50 KwikPen", "Humalog Mix75/25", "Humalog Mix75/25", "Humalog Mix75/25", "Humalog Mix75/25 KwikPen", "Humalog Pen", "Humalog Pen", "Humalog Tempo Pen", "Humalog Tempo Pen", "Humalog Tempo Pen", "Insulin lispro", "Insulin Lispro", "Insulin lispro", "Insulin Lispro", "Insulin Lispro", "Insulin Lispro Junior KwikPen", "Insulin Lispro KwikPen", "Insulin Lispro KwikPen", "Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen", "Insulin Lispro Sanofi", "Insulin Lispro Sanofi", "Insulin Lispro Sanofi", "Insulin Lispro Sanofi", "Insulin Lispro Sanofi", "Insulin Lispro Sanofi", "Insulin Lispro Sanofi", "Insulin Lispro Sanofi", "Liprelog", "Liprelog", "Liprelog", "Liprelog", "Liprolog", "Liprolog", "Liprolog", "Liprolog", "Liprolog", "Liprolog Basal", "Liprolog Basal", "Liprolog Basal Kwikpen", "Liprolog Basal Kwikpen", "Liprolog Junior Kwikpen", "Liprolog Junior Kwikpen", "Liprolog Kwikpen", "Liprolog Kwikpen", "Liprolog Kwikpen", "Liprolog Kwikpen", "Liprolog Mix25", "Liprolog Mix25", "Liprolog Mix25 Kwikpen", "Liprolog Mix25 Kwikpen", "Liprolog Mix50", "Liprolog Mix50", "Liprolog Mix50 Kwikpen", "Liprolog Mix50 Kwikpen", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev", "Lyumjev (kwikpen)", "Lyumjev (kwikpen)", "LYUMJEV Junior KwikPen", "LYUMJEV Junior KwikPen", "LYUMJEV KwikPen", "LYUMJEV KwikPen", "LYUMJEV KwikPen", "LYUMJEV KwikPen", "LYUMJEV Tempo Pen", "LYUMJEV Tempo Pen", "Lyumjev Tempo Pen", "Lyumjev Tempo Pen" ]

[]

[ "Humalog Mix 25 (cartridge)", "Humalog Mix 25 (cartridge)", "Humalog Mix 50 (cartridge)", "Humalog Mix 50 (cartridge)", "Humalog Mix 25 (kwikpen)", "Humalog Mix 25 (kwikpen)", "Humalog Mix 25 (pen)", "Humalog Mix 25 (pen)", "Humalog Mix 50 (kwikpen)", "Humalog Mix 50 (kwikpen)" ]

[ "P06213", "P08069" ]

[ "P05177", "P14735" ]

[]

DB00047

Insulin glargine

Insulin glargine is a long-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Insulin is typically prescribed for the management of diabetes mellitus to mimic the activity of endogenously produced human insulin, a peptide hormone produced by beta cells of the pancreas that promotes glucose metabolism. Insulin is released from the pancreas following a meal to promote the uptake of glucose from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscle. Absorption of glucose into cells allows for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, enhances protein synthesis, and inhibits lipolysis and proteolysis. Insulin is an important treatment in the management of Type 1 Diabetes (T1D), which is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting in the body not being able to produce or synthesize the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin, such as insulin glargine, to lower glucose levels in the blood. Insulin is also used in the treatment of Type 2 Diabetes (T2D), another form of diabetes mellitus that is a slowly progressing metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Without treatment or improvement in non-pharmacological measures such as diet and exercise to lower blood glucose, high blood sugar eventually causes cellular resistance to endogenous insulin, and in the long term, damage to pancreatic islet cells. Insulin is typically prescribed later in the course of T2D, after several oral medications such as [DB00331], [DB01120], or [DB01261] have been tried, when sufficient damage has been caused to pancreatic cells that the body is no longer able to produce insulin on its own. Available as the brand name product Lantus, insulin glargine has a duration of action up to 24 hours allowing for once-daily dosing, typically at bedtime. Due to its duration of action, Lantus is considered "basal insulin" as it provides low concentrations of background insulin that can keep blood sugar stable between meals or overnight. Basal insulin is often combined with short-acting "bolus insulin" such as [DB00046], [DB01309], and [DB01306] to provide higher doses of insulin that are required following meals. Use of basal and bolus insulin together is intended to mimic the pancreas' production of endogenous insulin, with a goal of avoiding any periods of hypoglycemia. Insulin glargine is also available as the biosimilar, or "follow-on" product, Basaglar in the US and as Abasaglar in the EU. As of 2015, insulin glargine was reformulated by Sanofi as the product Toujeo in an extra-concentrated form containing 300IU/mL (compared to 100IU/mL contained in Lantus). Use of the higher concentrated Toujeo as compared to Lantus results in slightly different pharmacokinetics, with a later onset (up to 6 hours) and duration of action (up to 30 hours). In 2021, another biosimilar, Semglee (insulin glargine-yfgn),[L34959] became the first interchangeable (with Lantus) biosimilar insulin to receive FDA approval.[L34964] Insulin glargine is produced by recombinant DNA technology using a non-pathogenic laboratory strain of Escherichia coli (K12) as the production organism. Insulin glargine differs from endogenous human insulin by the replacement of an asparagine residue at position A21 of the A-chain with glycine and addition of two arginines to the C-terminus (positions B31 and 32) of the B-chain. The resulting protein is soluble at pH 4 and forms microprecipitates at physiological pH 7.4 allowing for the slow release of small amounts of insulin glargine, giving the drug a long duration of action and no pronounced peak concentration. Without an adequate supply of insulin to promote absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high levels and can result in symptoms such as fatigue, headache, blurred vision, and increased thirst. If left untreated, the body starts to break down fat, instead of glucose, for energy which results in a build-up of ketone acids in the blood and a syndrome called ketoacidosis, which is a life-threatening medical emergency. In the long term, elevated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy.

liquid

Insulin glargine is indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus.[L12474,L43532,L43587]

Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, the pancreas produces a continuous supply of low levels of basal insulin along with spikes of insulin following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin glargine is a long-acting insulin analogue with a flat and predictable action profile. It is used to mimic the basal levels of insulin in diabetic individuals.

Insulin glargine binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signalling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism. Insulin glargine is completely soluble at pH 4, the pH of administered solution, and has low solubility at physiological pH 7.4. Upon subcuteous injection, the solution is neutralized resulting in the formation of microprecipitates. Small amounts of insulin glargine are released from microprecipitates giving the drug a relatively constant concentration over time profile over 24 hours with no pronounced peak. This release mechanism allows the drug to mimic basal insulin levels within the body.

Because of the modifications to the A and B chain, the isoelectric point shifts towards a neutral pH and insulin glargine is more stable in acidic conditions than regular insulin. As insulin glargine is less soluble at neutral pH, once injected, forms microprecipitates. Slow release of insulin glargine from microprecipitates provides a relatively constant concentration of insulin over 24 hours. Onset of action is approximately 1.1 hours. The pharmacokinetic profiles for single 0.4, 0.6, and 0.9 U/kg doses of Toujeo in 24 patients with type 1 diabetes mellitus was evaluated in a euglycemic clamp study. The median time to maximum serum insulin concentration was 12 (8–14), 12 (12–18), and 16 (12–20) hours, respectively. Steady-state insulin concentrations are reached by at least 5 days of once-daily subcutaneous administration of 0.4 U/kg to 0.6 U/kg doses of Toujeo over 8 days in patients with type 1 diabetes mellitus. The median time to maximum effect of Basaglar (measured by the peak rate of glucose infusion) was approximately 12.0 hours. The pharmacodynamic profile of Basaglar following subcutaneous injection demonstrated sustained glucose lowering activity over 24 hours with no pronounced peak. The mean area under the glucose infusion rate curves (measure of overall pharmacodynamic effect) and maximum glucose infusion rate were 1670 mg/kg and 2.12 mg/kg/min, respectively. On average, serum insulin concentrations declined to baseline by approximately 24 hours.

Insulin glargine is metabolized in the liver into two active metabolites with similar activity to insulin: 21a-Gly-human insulin (M1) and 21a-Gly-des-30b- threonine insulin (M2), with M1 being the predominant metabolite.

Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. Other adverse events that may occur include allergic reaction, injection site reaction, lipodystrophy, pruritis, and rash.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "A10AE", "A10A", "A10", "A", "A10AE", "A10A", "A10", "A" ]

[ "Humans and other mammals" ]

[ { "cost": "14.35", "description": "Lantus 100 unit/ml cartridge", "unit": "ml" }, { "cost": "14.35", "description": "Lantus solostar 100 unit/ml", "unit": "ml" }, { "cost": "44.78", "description": "Lantus for OptiClik 100 unit/ml Solution 3ml Cartridge", "unit": "cartridge" }, { "cost": "111.88", "description": "Lantus 100 unit/ml Solution 10ml Vial", "unit": "vial" }, { "cost": "223.89", "description": "Lantus SoloStar 100 unit/ml Solution 1 Box = Five 3ml Syringes", "unit": "box" } ]

[ { "approved": "2000-08-08", "country": "United States", "expires": "2009-11-06", "number": "6100376" }, { "approved": "1997-04-01", "country": "Canada", "expires": "2014-04-01", "number": "1339044" }, { "approved": "2015-04-21", "country": "United States", "expires": "2024-03-26", "number": "9011391" }, { "approved": "2016-01-12", "country": "United States", "expires": "2024-03-02", "number": "9233211" }, { "approved": "2013-12-10", "country": "United States", "expires": "2024-03-02", "number": "8603044" }, { "approved": "2013-08-20", "country": "United States", "expires": "2024-09-15", "number": "8512297" }, { "approved": "2014-03-25", "country": "United States", "expires": "2025-04-12", "number": "8679069" }, { "approved": "2015-03-31", "country": "United States", "expires": "2024-06-05", "number": "8992486" }, { "approved": "2013-10-15", "country": "United States", "expires": "2024-03-03", "number": "8556864" }, { "approved": "2011-04-05", "country": "United States", "expires": "2028-03-23", "number": "7918833" }, { "approved": "2010-05-11", "country": "United States", "expires": "2023-12-13", "number": "7713930" }, { "approved": "2009-01-13", "country": "United States", "expires": "2024-01-23", "number": "7476652" }, { "approved": "2017-02-07", "country": "United States", "expires": "2024-08-28", "number": "9561331" }, { "approved": "2017-04-18", "country": "United States", "expires": "2024-08-19", "number": "9623189" }, { "approved": "2017-04-04", "country": "United States", "expires": "2024-03-02", "number": "9610409" }, { "approved": "2016-12-27", "country": "United States", "expires": "2024-03-02", "number": "9526844" }, { "approved": "2017-03-28", "country": "United States", "expires": "2024-03-02", "number": "9604008" }, { "approved": "2017-01-03", "country": "United States", "expires": "2024-08-17", "number": "9533105" }, { "approved": "2016-08-09", "country": "United States", "expires": "2024-03-02", "number": "9408979" }, { "approved": "2017-03-28", "country": "United States", "expires": "2024-08-16", "number": "9604009" }, { "approved": "2014-12-30", "country": "United States", "expires": "2020-07-12", "number": "RE45313" }, { "approved": "2016-12-27", "country": "United States", "expires": "2029-10-09", "number": "9526764" }, { "approved": "2016-05-24", "country": "United States", "expires": "2031-05-18", "number": "9345750" }, { "approved": "2017-07-18", "country": "United States", "expires": "2030-11-11", "number": "9707176" }, { "approved": "2017-10-03", "country": "United States", "expires": "2024-03-02", "number": "9775954" }, { "approved": "2017-11-28", "country": "United States", "expires": "2024-03-02", "number": "9827379" }, { "approved": "2017-11-21", "country": "United States", "expires": "2032-05-09", "number": "9821032" }, { "approved": "2018-04-24", "country": "United States", "expires": "2035-12-10", "number": "9950039" }, { "approved": "2017-08-01", "country": "United States", "expires": "2033-04-08", "number": "9717852" }, { "approved": "2018-07-24", "country": "United States", "expires": "2032-08-02", "number": "10029011" }, { "approved": "2018-11-06", "country": "United States", "expires": "2029-10-09", "number": "10117909" }, { "approved": "2019-08-06", "country": "United States", "expires": "2035-09-16", "number": "10369291" } ]

[ "Abasaglar", "Abasaglar", "Abasaglar", "Abasaglar", "Abasaglar", "Abasaglar", "Abasaglar", "Abasaglar", "Abasaglar", "Abasaglar", "Abasaglar", "Abasaglar", "Abasaglar", "Abasaglar", "Abasaglar", "Basaglar", "Basaglar", "Basaglar", "Basaglar", "BASAGLAR KwikPen", "BASAGLAR Tempo Pen", "Insulin Glargine", "Insulin Glargine", "Insulin Glargine", "Insulin Glargine", "Insulin Glargine", "Insulin Glargine", "Insulin Glargine", "Insulin Glargine Solostar", "Insulin Glargine Solostar", "Insulin Glargine Solostar", "Insulin glargine U-300", "Insulin glargine U-300 Max", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus", "Lantus Solostar", "Lantus Solostar", "Lantus Solostar", "Lantus Solostar", "Lantus Solostar", "Rezvoglar KwikPen", "Rezvoglar Kwikpen", "Semglee", "Semglee", "Semglee", "Semglee", "Semglee", "Semglee", "Semglee", "Semglee", "Semglee", "Semglee", "Semglee", "Semglee", "Soliqua", "Soliqua 100/33", "Suliqua", "Suliqua", "Suliqua", "Suliqua", "Suliqua", "Suliqua Pen", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo", "Toujeo Doublestar", "TOUJEO Max", "TOUJEO Max", "Toujeo Solostar" ]

[ "Lantus R", "Lusduna Nexvue", "Optisulin", "Semglee" ]

[ "Soliqua 100/33", "Soliqua", "Suliqua", "Suliqua", "Suliqua", "Suliqua", "Suliqua", "Suliqua Pen" ]

[ "P06213", "P08069" ]

[ "P05177" ]

[]

DB00048

Collagenase clostridium histolyticum

Collagenase clostridium histolyticum is an enzyme produced by the bacterium Clostridium histolyticum. It is beneficial in the breakdown of collagen plaques for the treatment of Dupuytren's contracture and Peyronie's disease.[L14882] The topical formulation is used for the debridement of necrotic tissue due to burns or chronic ulcers.[L14912] On July 6, 2020 a combination of injectable bacterial collagenases was approved by the FDA for the treatment of cellulite in adult women.[L14872] Also known as Qwo, this injection is the first approved injectable treatment for cellulite and was developed by Endo International.[L14892]

solid

Collagenase clostridium histolyticum is indicated for the treatment of adults with Dupuytren's contracture with a palpable cord. Additionally, it is used to treat men with Peyronie's disease diagnosed with a penile curvature deformity of at least a 30-degree angle at the beginning of therapy in addition to palpable plaques.[L14882] Collagenase ointment is used for the tissue debridement of chronic dermal ulcers and severely burned tissues.[L14952] The combination collagenase product, also known as Qwo, is used for the treatment of moderate to severe cellulite in the buttocks of adult women.[L14872]

Collagenase digests collagen, treating conditions such as Peyronie's disease, cellulite, chronic ulcers, burns, and contractures.[L14872,L14882,L14912]

Peyronie's disease is a fibrous lesion of the tunica albuginea in the penile tissues.[A215067] Cellulite is a multifactorial condition resulting in the accumulation of fibrotic dermal septae and the expansion of subcutaneous fat.[A215062] Dupuytren's contracture is a fibroproliferative disease that results in the fibrous deposition of collagen in the hands, limiting mobility and functionality of the hands.[A215072] The collagen deposition in the abovementioned conditions is the target of collagenase enzyme therapy.[A215157,A215167] These enzymes are proteinases acting to hydrolyze collagen's triple-helical conformation, resulting in the lysis of collagen deposits and relief from the necrotic tissue and plaques associated with several conditions.[L14882,L14912] On a molecular level, collagenases cleave polypeptide chains that make up the collagen triple helix structure at various loci, leading to solubilization from the collagen fibril.[A215197]

There is currently limited readily available regarding the absorption of collagenase through the skin.[L14912] In a pharmacokinetic study, the serum concentrations of clostridium type I collagenase (AUX-I) and clostridium type II collagenase (AUX-II) were measured. Both were detected under the lower limit of quantitation of 5 ng/mL and 25 ng/mL, respectively, in volunteers administered one dose of the collagenase histolyticum combination product, Qwo, at a dose of up to 3.36 mg in a maximum of 4 body areas.[L14872]

No formal systemic metabolism studies have been performed with collagenase histolyticum.[A215277]

No clinical reaction has been attributed to an overdose of collagenase in clinical trials.[L14912] If required, the collagenase enzymes can be inactivated with a povidone-iodine wash.[L14912]

null

There is no readily available information regarding the protein binding of collagenase.[L14912]

null

There is no currently available information regarding the presence of collagenase in body fluids or uptake by particular organs and passage through the blood-brain barrier.[L14912] Systemic pharmacokinetic studies evaluation volume of distribution have not been performed, however, collagenase histolyticum is likely to have local degradative effects in the region of the application without effects on the vasculature and elastic tissue.[A215277]

Clearance information for collagenase is not readily available.[L14912]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "D03BA", "D03B", "D03", "D", "M09AB", "M09A", "M09", "M", "D03BA", "D03B", "D03", "D" ]

[ "Humans and other mammals" ]

[ { "cost": "4.13", "description": "Santyl ointment", "unit": "g" }, { "cost": "62.98", "description": "Santyl 250 unit/gm Ointment 15 gm Tube", "unit": "tube" }, { "cost": "2432.7", "description": "Collagenase powder", "unit": "g" }, { "cost": "3900.0", "description": "Xiaflex 0.9 mg vial", "unit": "vial" } ]

[]

[ "Collagen Film", "Collagenase Santyl", "Collagenase Santyl", "Kimchi Vitamin chewable multivitamin", "Qwo", "Santyl", "Xiaflex", "Xiaflex", "Xiapex" ]

[ "Cordase" ]

[ "Kimchi Vitamin chewable multivitamin", "Collagen Film" ]

[ "P02452", "P02458", "P02461" ]

[]

DB00049

Rasburicase

Rasburicase is a recombinant urate-oxidase enzyme produced by a genetically modified Saccharomyces cerevisiae strain. The cDNA coding for rasburicase was cloned from a strain of _Aspergillus flavus_.

liquid

For treatment of hyperuricemia, reduces elevated plasma uric acid levels (from chemotherapy)

Drugs used to treat lympohoid leukemia, non-Hodgkin's lymphoma and acute myelogenous leukemia often lead to the accumulation of toxic plasma levels of purine metabolites (i.e. uric acid). The injection of rasburicase reduces levels of uric acid and mitigates the toxic effects of chemotherapy induced tumor lysis.

Rasburicase catalyzes enzymatic oxidation of uric acid into an inactive and soluble metabolite (allantoin).

null

18 hours

null

* 110 to 127 mL/kg [pediatric patients] * 75.8 to 138 mL/kg [adult patients]

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "V03AF", "V03A", "V03", "V", "M04AX", "M04A", "M04", "M" ]

[ "Humans and other mammals" ]

[ { "cost": "627.23", "description": "Elitek 1.5 mg vial", "unit": "vial" }, { "cost": "3136.18", "description": "Elitek 7.5 mg vial", "unit": "vial" } ]

[ { "approved": "2003-12-30", "country": "Canada", "expires": "2016-05-07", "number": "2175971" }, { "approved": "2002-07-16", "country": "Canada", "expires": "2015-05-03", "number": "2148537" } ]

Rasburicasa | Rasburicase | Recombinant urate oxidase | Urate oxidase

[ "Elitek", "Elitek", "Fasturtec", "Fasturtec", "Fasturtec", "Fasturtec" ]

[]

DB00050

Cetrorelix

Cetrorelix is a man-made hormone that blocks the effects of Gonadotropin Releasing Hormone (GnRH). GnRH controls another hormone that is called luteinizing hormone (LH), which is the hormone that starts ovulation during the menstrual cycle. When undergoing hormone treatment sometimes premature ovulation can occur, leading to eggs that are not ready for fertilization to be released. Cetrorelix does not allow the premature release of these eggs to occur.

solid

For the inhibition of premature LH surges in women undergoing controlled ovarian stimulation

Cetrorelix is a synthetic decapeptide with gonadotropin-releasing hormone (GnRH) antagonistic activity. GnRH induces the production and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the gonadotrophic cells of the anterior pituitary. Due to a positive estradiol (E2) feedback at midcycle, GnRH liberation is enhanced resulting in an LH-surge. This LH-surge induces the ovulation of the dominant follicle, resumption of oocyte meiosis and subsequently luteinization as indicated by rising progesterone levels. Cetrorelix competes with natural GnRH for binding to membrane receptors on pituitary cells and thus controls the release of LH and FSH in a dose-dependent manner.

Cetrorelix binds to the gonadotropin releasing hormone receptor and acts as a potent inhibitor of gonadotropin secretion. It competes with natural GnRH for binding to membrane receptors on pituitary cells and thus controls the release of LH and FSH in a dose-dependent manner.

Rapidly absorbed following subcutaneous injection. The mean absolute bioavailability following subcutaneous administration to healthy female subjects is 85%.

In in vitro studies, cetrorelix was stable against phase I- and phase II-metabolism. Cetrorelix was transformed by peptidases, and the (1-4) peptide was the predominant metabolite.

null

~62.8 hours

86%

Following subcutaneous administration of 10 mg cetrorelix to males and females, only unchanged cetrorelix was detected in urine.

* 1.16 L/kg

* 1.28 ml/min·kg [adult healthy female with 3 mg single SC administration]

Organic compounds

Organic Polymers

Polypeptides

null

[ "approved", "investigational" ]

[ "H01CC", "H01C", "H01", "H" ]

[ "Humans and other mammals" ]

[ { "cost": "137.99", "description": "Cetrotide 0.25 mg kit", "unit": "kit" }, { "cost": "689.92", "description": "Cetrotide 3 mg kit", "unit": "kit" } ]

[ { "approved": "1993-03-30", "country": "United States", "expires": "2010-10-24", "number": "5198533" }, { "approved": "2003-08-05", "country": "Canada", "expires": "2014-02-18", "number": "2115943" }, { "approved": "2001-11-20", "country": "United States", "expires": "2019-04-23", "number": "6319192" } ]

[ "Cetrorelix", "Cetrorelix", "Cetrorelix acetate", "Cetrorelix acetate", "Cetrorelix Acetate", "Cetrorelix Acetate", "Cetrorelix Acetate", "Cetrotide", "Cetrotide", "Cetrotide", "Cetrotide", "Cetrotide", "Cetrotide" ]

[]

[ "P30968", "P22888" ]

[]

DB00051

Adalimumab

Adalimumab is a subcutaneously administered biological disease modifier for the treatment of rheumatoid arthritis and other chronic debilitating diseases mediated by tumor necrosis factor.[A39984,A39999] It was originally launched by Abbvie in the U.S. and approved in 2002 by the FDA.[A39983] This drug is frequently known as _Humira_. It is produced by recombinant DNA technology using a mammalian cell expression system. This drug is available in a prefilled syringe form and convenient pen form for subcutaneous self-administered doses.[A39983] Several biosimilars to adalimumab. Adalimumab-atto was the first adalimumab biosimilar approved by the FDA in 2016.[L44953] Adalimumab-adaz was approved by the FDA on October 31, 2018.[L4799] Other biosimilars include adalimumab-fkjp - which was approved in July 2022 -,[L42495] adalimumab-bwwd - which was approved in August 2022 -,[L42935] and adalimumab-aacf - which was approved in October 2023.[L49101] A biosimilar marketed as Hyrimoz, a high-concentration formulation of adalimumab, is also available.[L45643,L45818]

liquid

Adalimumab is indicated for the following conditions:[L49101] - Moderately to severely active Rheumatoid Arthritis (RA) in adults, as monotherapy or in combination with [methotrexate] or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs).[L42290, L42495, L42935, L44953, L45643, L45818, L49101] - Moderately to severely active polyarticular Juvenile Idiopathic Arthritis (JIA) in patients two years of age and older, as monotherapy or in combination with [methotrexate].[L42290, L42495, L42935, L44953, L45643, L45818, L49101] - Psoriatic Arthritis (PsA) in adults.[L42290, L42495, L42935, L44953, L45643, L45818, L49101] - Ankylosing Spondylitis (AS) in adults.[L42290, L42495, L42935, L44953, L45643, L45818, L49101] - Moderately to severely active Crohn’s Disease (CD) in adults and pediatric patients six years of age and older.[L42290, L42495, L42935, L44953, L45643, L45818, L49101] - Moderately to severely active Ulcerative Colitis (UC) in adults. Effectiveness has not been established in patients who have lost response to or were intolerant to TNF blockers.[L42290, L42495, L42935, L44953, L45643, L45818, L49101] - Moderate to severe chronic plaque psoriasis in adult candidates for systemic therapy or phototherapy and when other systemic therapies are medically less appropriate.[L42290, L42495, L42935, L44953, L45643, L45818, L49101] - Moderate to severe Hidradenitis Suppurativa (HS) in adults.[L44953] - Non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients two years of age and older.[L35370] Adalimumab has also been used off-label to treat Pyoderma gangrenosum.[A40001,A40002]

After treatment with adalimumab, a decrease in levels of acute phase reactant proteins of inflammation (C reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and serum cytokines (IL-6) was measured compared to baseline in patients diagnosed with rheumatoid arthritis. A decrease in CRP levels was also observed in patients diagnosed with Crohn’s disease. Serum levels of matrix metalloproteinases (MMP-1 and MMP-3) that lead to the tissue remodeling responsible for cartilage destruction were also found to be decreased after administration of adalimumab.[L35370] A reduction in signs and symptoms of disease, the induction of clinical response, inhibition of structural damage, and improvements in physical function in adult and pediatric patients with various inflammatory conditions have been demonstrated.[A39983, A39999, L35370]

Adalimumab binds with specificity to tumor necrosis factor-alpha (TNF-alpha) and inhibits its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab also lyses surface tumor necrosis factor expressing cells in vitro when in the presence of complement.[A39984,A39999] Adalimumab does not bind or inactivate lymphotoxin (Tumor necrosis factor-beta). TNF is a naturally occurring cytokine that plays a role in normal inflammatory and immune responses.[A39999] Increased levels of TNF are found in the joint synovial fluid of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis patients, and play an imperative role in pathologic inflammation and joint destruction that are major complications of these diseases. Increased levels of TNF are also measured in psoriasis plaques. In plaque psoriasis, treatment with adalimumab may decrease the epidermal thickness and inflammatory cell infiltration. The relationship between these pharmacodynamics and the mechanism(s) by which adalimumab achieves its clinical effects is not known. Additionally, adalimumab alters biological responses that are induced/regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration during inflammation (ELAM-1, VCAM-1, and ICAM-1 with an IC50 of 1-2 X 10-10M).[L35370]

The maximum serum concentration (Cmax) and the time to reach the maximum concentration (Tmax) were 4.7 ± 1.6 μg/mL and 131 ± 56 hours respectively, following a single 40 mg subcutaneous administration of adalimumab to healthy adult subjects. The average absolute bioavailability of adalimumab estimated from three clinical studies after a single 40 mg subcutaneous dose of adalimumab was 64%. The pharmacokinetics of adalimumab showed a linear pattern over the dose range of 0.5 to 10.0 mg/kg following a single intravenous dose.[L35370]

null

Doses up to 10 mg/kg have been administered to patients in clinical trials without evidence of dose-limiting toxicities. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately.[L42290]

The mean terminal half-life was approximately 2 weeks, ranging from 10 to 20 days across studies.[L35370]

null

Adalimumab is most likely removed by opsonization via the reticuloendothelial system.[A40006]

The distribution volume (Vss) ranged from 4.7 to 6.0 L following intravenous administration of doses ranging from 0.25 to 10 mg/kg in RA patients.[L35370]

The single-dose pharmacokinetics of adalimumab in RA patients were determined in several studies with intravenous doses ranging from 0.25 to 10 mg/kg. The systemic clearance of adalimumab is approximately 12 mL/hr. In long-term studies with dosing more than two years, there was no evidence of changes in clearance over time in RA patients.[L35370]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "experimental" ]

[ "L04AB", "L04A", "L04", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "959.19", "description": "Humira 20 mg/0.4 ml syringe", "unit": "syringe" }, { "cost": "959.19", "description": "Humira 40 mg/0.8 ml pen", "unit": "pen" }, { "cost": "959.19", "description": "Humira crohn's starter pack", "unit": "each" }, { "cost": "959.19", "description": "Humira psoriasis starter pack", "unit": "each" }, { "cost": "1995.1", "description": "Humira (1 Box = Two 40 mg/0.8ml Syringes) Box", "unit": "box" }, { "cost": "1995.1", "description": "Humira 2 20 mg/0.4ml Kit 1 Box = Two 20 mg/0.4ml Syringes", "unit": "box" }, { "cost": "1995.1", "description": "Humira Pen 2 40 mg/0.8ml Kit (1 Box = 1 Kit Containing Two 40 mg/0.8ml Pens)", "unit": "box" } ]

[ { "approved": "2002-09-17", "country": "Canada", "expires": "2017-02-10", "number": "2243459" } ]

[ "Abrilada", "Abrilada", "Abrilada", "Abrilada", "Abrilada", "Abrilada", "Abrilada", "Abrilada", "Abrilada", "Abrilada", "Abrilada", "Abrilada", "Abrilada", "Abrilada", "Abrilada", "Abrilada", "Adalimumab", "Adalimumab", "Adalimumab", "Adalimumab", "Adalimumab", "Adalimumab", "Adalimumab", "Adalimumab", "Adalimumab", "Adalimumab", "Adalimumab", "Adalimumab", "Adalimumab", "Adalimumab", "Adalimumab-aacf", "Adalimumab-aacf", "Adalimumab-adbm", "Adalimumab-adbm", "Adalimumab-adbm", "Adalimumab-adbm", "Adalimumab-adbm", "Adalimumab-adbm", "Adalimumab-adbm", "Adalimumab-adbm", "Adalimumab-adbm", "Adalimumab-adbm", "Adalimumab-ryvk", "Adalimumab-ryvk", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amgevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amjevita", "Amsparity", "Amsparity", "Amsparity", "Amsparity", "Amsparity", "Amsparity", "Amsparity", "Amsparity", "Amsparity", "Amsparity", "Cyltezo", "Cyltezo", "Cyltezo", "Cyltezo", "Cyltezo", "Cyltezo", "Cyltezo", "Cyltezo", "Cyltezo", "Cyltezo", "Cyltezo", "Cyltezo", "Cyltezo", "Cyltezo", "Hadlima", "Hadlima", "Hadlima", "Hadlima", "Hadlima", "Hadlima", "Hadlima", "Hadlima", "Hadlima", "Hadlima", "Hadlima", "Hadlima", "Hadlima", "Hadlima Pushtouch", "Hadlima Pushtouch", "Halimatoz", "Halimatoz", "Halimatoz", "Halimatoz", "Halimatoz", "Halimatoz", "Halimatoz", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hefiya", "Hukyndra", "Hukyndra", "Hukyndra", "Hukyndra", "Hukyndra", "Hukyndra", "Hukyndra", "Hukyndra", "Hukyndra", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Hulio", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Humira", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Hyrimoz", "Idacio", "Idacio", "Idacio", "Idacio", "Idacio", "Idacio", "Idacio", "Idacio", "Idacio", "Idacio", "Idacio", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Imraldi", "Kromeya", "Kromeya", "Kromeya", "Kromeya", "Kromeya", "Libmyris", "Libmyris", "Libmyris", "Libmyris", "Libmyris", "Libmyris", "Libmyris", "Sb5 (biib606)", "Simlandi", "Simlandi", "Simlandi", "Simlandi", "Simlandi", "Simlandi", "Simlandi", "Solymbic", "Solymbic", "Solymbic", "Solymbic", "Solymbic", "Solymbic", "Solymbic", "Solymbic", "Solymbic", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yuflyma", "Yusimry", "Yusimry", "Yusimry", "Yusimry" ]

[ "Amjevita", "Cyltezo", "Humira Pen" ]

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[ "P01375" ]

[]

DB00052

Somatotropin

Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names.

liquid

Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493]

Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398]

In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183]

When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971]

Information is unavailable.

The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971]

When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971]

While there is no information regarding the protein binding profile of recombinant human growth hormones, endogenous growth hormone is typically complexed with growth hormone-binding protein, which is a soluble form of growth hormone receptor, when it is incubated with plasma _in vitro_.[A228463]

Information is unavailable.

Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean clearance rate was approximately 2.3 (±1.8) mL/min/kg or 139 (±105) mL/min.[L10971]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "H01AC", "H01A", "H01", "H" ]

[ "Humans and other mammals" ]

[ { "cost": "15.05", "description": "Genotropin miniquick 0.2 mg", "unit": "each" }, { "cost": "30.09", "description": "Genotropin miniquick 0.4 mg", "unit": "each" }, { "cost": "45.14", "description": "Genotropin miniquick 0.6 mg", "unit": "each" }, { "cost": "60.19", "description": "Genotropin miniquick 0.8 mg", "unit": "each" }, { "cost": "75.23", "description": "Genotropin miniquick 1 mg", "unit": "each" }, { "cost": "77.36", "description": "Genotropin MiniQuick 1 mg (7 Cartridges Per Box)", "unit": "cartridge" }, { "cost": "90.28", "description": "Genotropin miniquick 1.2 mg", "unit": "each" }, { "cost": "92.83", "description": "Genotropin MiniQuick 1.2 mg (7 Cartridges Per Box)", "unit": "cartridge" }, { "cost": "105.32", "description": "Genotropin miniquick 1.4 mg", "unit": "each" }, { "cost": "108.78", "description": "Genotropin MiniQuick 1.4 mg (7 Cartridges Per Box)", "unit": "cartridge" }, { "cost": "110.52", "description": "Genotropin MiniQuick 0.2 mg (7 Cartridges Per Box)", "unit": "box" }, { "cost": "120.37", "description": "Genotropin miniquick 1.6 mg", "unit": "each" }, { "cost": "123.78", "description": "Genotropin MiniQuick 1.6 mg (7 Cartridges Per Box)", "unit": "cartridge" }, { "cost": "135.41", "description": "Genotropin miniquick 1.8 mg", "unit": "each" }, { "cost": "150.46", "description": "Genotropin miniquick 2 mg", "unit": "each" }, { "cost": "154.72", "description": "Genotropin MiniQuick 2 mg (7 Cartridges Per Box)", "unit": "cartridge" }, { "cost": "221.9", "description": "Serostim 4 mg vial", "unit": "vial" }, { "cost": "228.45", "description": "Genotropin MiniQuick 0.4 mg (7 Cartridges Per Box)", "unit": "box" }, { "cost": "239.51", "description": "Tev-tropin 5 mg vial", "unit": "vial" }, { "cost": "259.45", "description": "Tev-Tropin 5 mg Solution Vial", "unit": "vial" }, { "cost": "274.95", "description": "Protropin 5 mg Solution Vial", "unit": "vial" }, { "cost": "277.38", "description": "Serostim 5 mg vial", "unit": "vial" }, { "cost": "283.38", "description": "Omnitrope 5.8 mg Solution Vial", "unit": "vial" }, { "cost": "326.67", "description": "Genotropin MiniQuick 0.6 mg (7 Cartridges Per Box)", "unit": "box" }, { "cost": "332.86", "description": "Serostim 6 mg vial", "unit": "vial" }, { "cost": "376.26", "description": "Saizen 5 mg vial", "unit": "vial" }, { "cost": "389.44", "description": "Norditropin 5 mg/1.5ml Solution 1.5ml Cartridge", "unit": "cartridge" }, { "cost": "389.44", "description": "Norditropin NordiFlex Pen 5 mg/1.5ml Solution 1 Syringe = 1.5ml", "unit": "pen" }, { "cost": "391.21", "description": "Genotropin 5.8 mg Cartridge", "unit": "cartridge" }, { "cost": "391.31", "description": "Saizen 5 mg Solution Vial", "unit": "vial" }, { "cost": "392.35", "description": "Nutropin 5 mg vial", "unit": "vial" }, { "cost": "418.66", "description": "Serostim 8.8 mg vial", "unit": "vial" }, { "cost": "433.56", "description": "Genotropin MiniQuick 0.8 mg (7 Cartridges Per Box)", "unit": "box" }, { "cost": "455.72", "description": "Humatrope 6 mg cartridge", "unit": "cartridge" }, { "cost": "549.9", "description": "Protropin 10 mg Solution Vial", "unit": "vial" }, { "cost": "602.02", "description": "Saizen 8.8 mg vial", "unit": "vial" }, { "cost": "626.1", "description": "Saizen 8.8 mg Solution Vial", "unit": "vial" }, { "cost": "626.1", "description": "Saizen Click.Easy 8.8 mg Solution Vial", "unit": "vial" }, { "cost": "748.92", "description": "Norditropin nordiflex 30 mg/3", "unit": "ml" }, { "cost": "753.86", "description": "Norditropin NordiFlex Pen 10 mg/1.5ml Solution 1 Syringe = 1.5ml", "unit": "pen" }, { "cost": "759.55", "description": "Nutropin aq 20 mg/2ml pen cart", "unit": "ml" }, { "cost": "759.55", "description": "Nutropin aq nuspin 20 pen cart", "unit": "ml" }, { "cost": "784.7", "description": "Nutropin 10 mg vial", "unit": "vial" }, { "cost": "911.45", "description": "Humatrope 12 mg cartridge", "unit": "cartridge" }, { "cost": "928.36", "description": "Genotropin 12 mg Solution", "unit": "each" }, { "cost": "1123.38", "description": "Norditropin 15 mg/1.5 ml cartridge", "unit": "ml" }, { "cost": "1123.38", "description": "Norditropin nordiflx 15 mg/1.5", "unit": "ml" }, { "cost": "1168.32", "description": "Norditropin 15 mg/1.5ml Solution 1.5ml Cartridge", "unit": "cartridge" }, { "cost": "1168.32", "description": "Norditropin NordiFlex Pen 15 mg/1.5ml Solution 1 Syringe = 1.5ml", "unit": "pen" }, { "cost": "1179.54", "description": "Norditropin flexpro 15 mg/1.5", "unit": "ml" }, { "cost": "1822.9", "description": "Humatrope 24 mg cartridge", "unit": "cartridge" } ]

[ { "approved": "1994-02-22", "country": "United States", "expires": "2011-10-07", "number": "5288703" }, { "approved": "2009-06-23", "country": "Canada", "expires": "2017-04-24", "number": "2252535" }, { "approved": "1994-01-25", "country": "Canada", "expires": "2011-01-25", "number": "1326439" }, { "approved": "2000-11-28", "country": "United States", "expires": "2018-11-20", "number": "6152897" }, { "approved": "1999-04-27", "country": "United States", "expires": "2016-04-27", "number": "5898030" }, { "approved": "2014-03-18", "country": "United States", "expires": "2022-07-02", "number": "8672898" }, { "approved": "2014-04-01", "country": "United States", "expires": "2026-04-20", "number": "8684969" }, { "approved": "2015-09-15", "country": "United States", "expires": "2032-08-01", "number": "9132239" }, { "approved": "2014-12-30", "country": "United States", "expires": "2027-01-17", "number": "8920383" }, { "approved": "2010-03-30", "country": "United States", "expires": "2026-08-03", "number": "7686786" }, { "approved": "2005-05-31", "country": "United States", "expires": "2022-07-01", "number": "6899699" }, { "approved": "2015-08-18", "country": "United States", "expires": "2026-07-26", "number": "9108002" }, { "approved": "2010-11-23", "country": "United States", "expires": "2021-07-21", "number": "RE41956" }, { "approved": "1999-12-21", "country": "United States", "expires": "2019-07-28", "number": "6004297" }, { "approved": "2012-11-27", "country": "United States", "expires": "2019-01-28", "number": "RE43834" }, { "approved": "1998-12-15", "country": "United States", "expires": "2015-12-15", "number": "5849700" }, { "approved": "1998-12-15", "country": "United States", "expires": "2015-12-15", "number": "5849704" }, { "approved": "2014-09-23", "country": "United States", "expires": "2017-12-26", "number": "8841252" }, { "approved": "2001-05-22", "country": "United States", "expires": "2019-01-28", "number": "6235004" }, { "approved": "2016-11-08", "country": "United States", "expires": "2022-07-02", "number": "9486588" }, { "approved": "2016-10-04", "country": "United States", "expires": "2028-03-27", "number": "9457154" }, { "approved": "2017-04-11", "country": "United States", "expires": "2027-02-03", "number": "RE46363" }, { "approved": "2017-06-27", "country": "United States", "expires": "2027-08-27", "number": "9687611" }, { "approved": "2017-10-03", "country": "United States", "expires": "2027-01-17", "number": "9775953" }, { "approved": "2018-01-09", "country": "United States", "expires": "2026-07-20", "number": "9861757" }, { "approved": "2017-04-11", "country": "United States", "expires": "2026-07-20", "number": "9616180" }, { "approved": "2010-07-27", "country": "United States", "expires": "2024-11-23", "number": "7762994" }, { "approved": "2013-11-12", "country": "United States", "expires": "2023-12-30", "number": "8579869" }, { "approved": "2019-03-05", "country": "United States", "expires": "2027-01-17", "number": "10220155" }, { "approved": "2019-07-23", "country": "United States", "expires": "2026-01-20", "number": "10357616" }, { "approved": "2019-08-13", "country": "United States", "expires": "2026-01-20", "number": "10376652" } ]

[ "Bio-tropin", "Bio-tropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Genotropin", "Humatrope", "Humatrope", "Humatrope", "Humatrope", "Humatrope", "Humatrope", "Humatrope", "Humatrope", "Norditropin", "Norditropin", "Norditropin", "Norditropin", "Norditropin", "Norditropin", "Norditropin", "Norditropin", "Norditropin Flexpro", "Norditropin Flexpro", "Norditropin Flexpro", "Norditropin Nordiflex", "Norditropin Nordiflex", "Norditropin Nordiflex", "Norditropin Simplexx", "Norditropin Simplexx", "Norditropin Simplexx", "Nutropin", "Nutropin", "Nutropin - Kit Pws(10mg) & Liq(10ml) Im Sc", "Nutropin - Kit Pws(5mg) & Liq(10ml) Im Sc", "Nutropin AQ", "Nutropin AQ - Sc 5mg/ml", "Nutropin AQ NuSpin 10", "Nutropin AQ NuSpin 10", "Nutropin AQ NuSpin 20", "Nutropin AQ NuSpin 20", "Nutropin AQ NuSpin 5", "Nutropin AQ NuSpin 5", "Nutropin AQ Pen 10", "Nutropin AQ Pen 20", "Nutropin AQ Pen Cartridge", "Nutropin Depot", "Nutropin Depot", "Nutropin Depot", "Nutropinaq", "Nutropinaq", "Nutropinaq", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Omnitrope", "Saizen", "Saizen", "Saizen", "Saizen", "Saizen", "Saizen", "Saizen 10iu - Kit", "Saizen 8.8mg (5.83mg/ml)", "Saizen Clickeasy", "Saizenprep", "Serostim", "Serostim", "Serostim", "Serostim", "Serostim", "Serostim", "Somatropin Biopartners", "Somatropin Biopartners", "Somatropin Biopartners", "Somatropin Biopartners", "Somatropin Biopartners", "Somatropin Biopartners", "Somatropin Biopartners", "Tev-tropin", "Tev-tropin", "Tev-tropin", "Valtropin", "Zomacton", "Zomacton", "Zomacton", "Zorbtive" ]

[ "BioTropin" ]

[ "Saizen 10iu - Kit", "Serostim", "Nutropin - Kit Pws(5mg) & Liq(10ml) Im Sc", "Nutropin - Kit Pws(10mg) & Liq(10ml) Im Sc", "Serostim", "Bio-tropin", "Bio-tropin", "Omnitrope", "Humatrope", "Humatrope", "Humatrope" ]

[ "P10912", "P16471" ]

[ "P05177", "P33261" ]

[]

[ "P08183" ]

DB00053

Imiglucerase

Human Beta-glucocerebrosidase or Beta-D-glucosyl-N-acylsphingosine glucohydrolase E.C. 3.2.1.45. 497 residue protein with N-linked carbohydrates, MW=59.3 kD. Alglucerase is prepared by modification of the oligosaccharide chains of human Beta-glucocerebrosidase. The modification alters the sugar residues at the non-reducing ends of the oligosaccharide chains of the glycoprotein so that they are predominantly terminated with mannose residues.

liquid

For the treatment of Gaucher's disease (deficiency in glucocerebrosidase)

Gaucher disease is characterized by a functional deficiency in Beta-glucocerebrosidase enzymatic activity and the resultant accumulation of lipid glucocerebroside in tissue macrophages which become engorged and are termed Gaucher cells. Gaucher cells are typically found in liver, spleen and bone marrow. This can lead to an enlarged spleen and liver (hepatosplenomegaly). Secondary hematologic sequelae include severe anemia and thrombocytopenia. Injections of imiglucerase into Gaucher disease patients leads to elevated serum levels of the enzyme and reduction in the accumulation of glucocerebroside leading to reduced anemia and thrombocytopenia, reduced spleen and liver size, and decreased cachexia

Imiglucerase catalyzes the hydrolysis of the glycolipid, glucocerebroside, to glucose and ceramide as part of the normal degradation pathway for membrane lipids.

null

3.6-10.4 min

null

* 0.09 to 0.15 L/kg

* 14.5 +/- 4.0 mL/min/kg

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "A16AB", "A16A", "A16", "A" ]

[ "Humans and other mammals" ]

[ { "cost": "380.64", "description": "Ceredase 80 unit/ml vial", "unit": "ml" }, { "cost": "951.6", "description": "Cerezyme 200 unit vial", "unit": "vial" }, { "cost": "1903.2", "description": "Cerezyme 400 unit vial", "unit": "vial" } ]

[ { "approved": "1996-08-27", "country": "United States", "expires": "2013-08-27", "number": "5549892" } ]

Imiglucerasa | Imiglucerase

[ "Cerezyme", "Cerezyme", "Cerezyme", "Cerezyme", "Cerezyme", "Cerezyme", "Cerezyme" ]

[]

DB00054

Abciximab

Abciximab is a Fab fragment of the chimeric human-murine monoclonal antibody 7E3. Abciximab binds to the glycoprotein (GP) IIb/IIIa receptor of human platelets and inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules. It also binds to vitronectin (αvβ3) receptor found on platelets and vessel wall endothelial and smooth muscle cells.

liquid

Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting.

Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes.

Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion.

null

Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally.

null

Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "B01AC", "B01A", "B01", "B" ]

[ "Humans and other mammals" ]

[ { "cost": "155.77", "description": "Reopro 2 mg/ml vial", "unit": "ml" } ]

[ { "approved": "2002-05-07", "country": "Canada", "expires": "2019-05-07", "number": "1341357" } ]

[ "Reopro", "Reopro", "Reopro" ]

[]

[ "P05106", "P08514", "P12318", "P31994", "P04004" ]

[]

DB00055

Drotrecogin alfa

Drotrecogin alfa is activated human protein C that is synthesized by recombinant DNA technology. It is a glycoprotein of approximately 55 kilodalton molecular weight, consisting of a heavy chain and a light chain linked by a disulfide bond. Drotrecogin alfa was withdrawn from the market after a major study indicated that it was not effective in improving outcomes in patients with sepsis.

liquid

For reduction of mortality in patients with severe sepsis.

Drotrecogin alfa is activated human protein C that is synthesized by recombinant DNA technology. It is a glycoprotein of approximately 55 kilodalton molecular weight, consisting of a heavy chain and a light chain linked by a disulfide bond. Drotrecogin alfa inhibits factor Va and VIIIa, thereby reducing the coagulability of blood.

Activated protein C combines with protein S on platelet surfaces and then degrades factor Va and factor VIIIa, thereby reducing blood coagulability.

null

5.5 hours (mammalian reticulocytes, in vitro).

null

* 40 L/hr [severe sepsis adults] * 30 +/- 8 L/hr [patients without sepsis undergoing hemodialysis] * 28 +/- 9 L/hr [heathy]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational", "withdrawn" ]

[ "B01AD", "B01A", "B01", "B" ]

[ "Humans and other mammals" ]

[ { "cost": "370.42", "description": "Xigris 5 mg vial", "unit": "vial" }, { "cost": "1481.66", "description": "Xigris 20 mg vial", "unit": "vial" } ]

[ { "approved": "2007-08-21", "country": "Canada", "expires": "2015-01-03", "number": "2139468" }, { "approved": "2002-01-15", "country": "Canada", "expires": "2011-02-22", "number": "2036894" } ]

[ "Xigris", "Xigris", "Xigris", "Xigris", "Xigris (20mg/vial)", "Xigris (5mg/vial)" ]

[]

[ "P00451", "P12259", "P05121", "P07204", "P07225", "P00734", "P02776", "P05154", "P35237", "Q9UNN8" ]

[]

DB00056

Gemtuzumab ozogamicin

Gemtuzumab ozogamicin is a recombinant humanized IgG4 kappa antibody which is conjugated with calicheamicin derivative, a cytotoxic antitumor antibiotic isolated from fermentation of Micromonospora echinospora ssp. calichensis. Gemtuzumab ozogamicin has approximately 50% of the antibody loaded with 4-6 moles calicheamicin per mole of antibody [FDA Label]. The antibody is specifically directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). By binding to the CD33 antigen on tumors, the cytotoxic agent blocks the growth of cancerous cells and causes cell death. Marketing approval of gemtuzumab ozogamicin was granted on May 17, 2000 by FDA as a treatment for patients with CD33-positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy [A98]. However, it was voluntarily withdrawn from the market in 2010 due to safety concerns, increased patient deaths and insufficient evidence of clinical benefit during confirmatory trials [L941]. On September 1 2017, gemtuzumab ozogamicin was again approved for the treatment of adults with newly diagnosed CD33-positive acute myeloid leukemia but with a lower dosing regimen and a different schedule in combination with chemotherapy or on its own [L941]. It is also indicated for the treatment of patients aged 2 years and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment (refractory) [L941].

liquid

Indicated for the treatment of patients with CD33 positive acute myeloid leukemia in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy. Indicated for the treatment of patients aged 2 years and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment (refractory).

Used for the treatment of acute myeloid leukemia (AML), mylotarg binds to the CD33 antigen, which is expressed on the surface of leukemic cells in more than 80% of patients with AML. The CD33 antigen is not expressed on pluripotent hematopoietic stem cells or nonhematopoietic cells. This gives mylotarg the selectivity needed to target leukemic cells.

Mylotarg is directed against the CD33 antigen expressed by hematopoietic cells. Binding of the anti-CD33 antibody portion of Mylotarg with the CD33 antigen results in the formation of a complex that is internalized. Upon internalization, the calicheamicin derivative is released inside the lysosomes of the myeloid cell. The released calicheamicin derivative binds to DNA in the minor groove resulting in site-specific DNA double strand breaks via formation of a p-benzene diradical [A20377]. Eventually, cell death is induced.

In pediatric patients receiving a dose level of 9mg/m^2, the peak plasma concentration (Cmax) was approximately 3.47±1.04 mg/L with the AUC of 136 ±107 mg * h/L [A20377].

Metabolic studies indicate hydrolytic release of the calicheamicin derivative from gemtuzumab ozogamicin. The drug is most likely removed by opsonization via the reticuloendothelial system.

The most frequently reported toxicities are myelosuppression and hepatic veno-occlusive disorder.

In pediatric patients receiving a dose level of 9mg/m^2, the half life was approximately 64±44 h after the first dose [A20377].

null

The volume of distribution at steady state (Vss) was approximately 6.5 ± 5.5 L in pediatric patients receiving a dose level of 9mg/m^2 [A20377].

The mean clearance rate was approximately 0.12±0.15 L/h/m^2 in pediatric patients receiving a dose level of 9mg/m^2 [A20377].

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L01FX", "L01F", "L01", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "3104.82", "description": "Mylotarg 5 mg vial", "unit": "vial" } ]

[ { "approved": "1998-06-30", "country": "United States", "expires": "2015-06-30", "number": "5773001" }, { "approved": "1996-12-17", "country": "United States", "expires": "2013-12-17", "number": "5585089" } ]

[ "Mylotarg", "Mylotarg", "Mylotarg" ]

[]

[ "P20138", "O75015", "P08637", "P12314" ]

[]

DB00057

Indium In-111 satumomab pendetide

Tumor associated glycoprotein (TAG) 72 (B72.3) monoclonal antibody conjugated with Indium 111 for radioimaging colon tumors. Satumomab Pendetide (trade name: OncoScint®) is no longer commercially available.

liquid

For diagnosis of extrahepatic malignant cancers

Binds to the tumor associated glycoprotein 72 antigen, which is a cell surface protein generally over-expressed in colorectal cancers. The radioactive Indium 111, which is covalently attached to the antibody, allows radiodiagnostic detection of TAG-72 expressing cells and tumors.

Satumomab Pendetide is a monoclonal antibody which is attached to the chelator pentetic acid (DTPA) linked to the tripeptide glycine (G) – L-tyrosine (Y) – L-lysine (K), which chelates Indium 111. Satumomab pendetide binds selectively to cell-surface TAG-72 expressed on colorectal tumors.

null

Most likely removed by opsonization via the reticuloendothelial system or by human antimurine antibody production

null

0.8 hours (mammalian reticulocytes, in vitro)

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "experimental", "withdrawn" ]

[ "V09IB", "V09I", "V09", "V" ]

[ "Humans and other mammals" ]

[]

Indium (111In) satumomab pendetide | Indium In 111 satumomab pendetide | Indium-111 satumomab pendetide

[]

[ "OncoScint" ]

[]

DB00058

Alpha-1-proteinase inhibitor

Human alpha-1 proteinase inhibitor or alpha-1-antitrypsin, prepared from human plasma via Cohn alcohol fractionation followed by PEG and zinc chloride fractionation.

liquid

For chronic augmentation and maintenance therapy in individuals with alpha1-proteinase inhibitor (A1-PI) deficiency and clinical evidence of emphysema.

Prevents excessive accumulation of active neutrophil elastase and consequent proteolysis of elastin tissues in alveolar lung structures. This prevents the development of emphysema.

Alpha-1 proteinase inhibitor is a serine protease inhibitor (Serpin). Its primary mechanism is inhibiting the action of the serine protease called elastase (also plasmin and thrombin) in the lungs. The reactive center loop (RCL) of alpha-1 proteinase inhibitor extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable.

null

* 5632 ± 2006 mL [ARALAST NP] * 5618 ± 1618 mL [Aralast]

* 940 +/- 275 mL/day [Patients with congenital α1-PI deficiency with single IV infusion of 60 mg/kg]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "B02AB", "B02A", "B02", "B" ]

[ "Humans and other mammals" ]

[ { "cost": "0.46", "description": "Prolastin 1000 mg vial", "unit": "vial" }, { "cost": "0.46", "description": "Prolastin 500 mg vial", "unit": "vial" }, { "cost": "0.46", "description": "Prolastin c 1000 mg vial", "unit": "vial" }, { "cost": "0.5", "description": "Aralast 500 mg vial", "unit": "vial" }, { "cost": "0.5", "description": "Zemaira 1000 mg vial", "unit": "vial" }, { "cost": "0.52", "description": "Aralast 1000 mg vial", "unit": "vial" }, { "cost": "0.52", "description": "Aralast np 1000 mg vial", "unit": "vial" }, { "cost": "0.52", "description": "Aralast np 500 mg vial", "unit": "vial" } ]

[]

[ "Alpha1-proteinase Inhibitor (human)", "Alpha1-proteinase Inhibitor (human)", "Aralast NP", "Aralast NP", "Aralast NP", "Aralast NP", "Aralast NP", "Glassia", "Glassia", "Prolastin Inj 25.0mg/ml", "Prolastin-C", "Prolastin-C", "Prolastin-C", "Prolastin-C", "Prolastin-C", "Prolastin-C Liquid", "Prolastin-C Liquid", "Pronextica Liquid", "Respreeza", "Respreeza", "Respreeza", "Zemaira", "Zemaira", "Zemaira", "Zemaira", "Zemaira", "Zemaira" ]

[ "Aralast", "Prolastin" ]

[ "Prolastin-C" ]

[ "P08246" ]

[]

DB00059

Pegaspargase

Pegaspargase is a conjugate of monomethoxypolyethylene glycol (mPEG) and L-asparaginase (L-asparagine amidohydrolase), an asparagine-specific enzyme that converts L-asparagine into aspartic acid and ammonia.[L44667] Asparagine is an amino acid that is vital for cell survival. In humans, most normal tissues can produce asparagine through the action of asparagine synthetase. However, leukemia cells have low levels of this enzyme and depend on exogenous sources. Therefore, the use of pegaspargase results in leukemic cell death.[A103,A255912,L44667] Pegaspargase has the same mechanism of action as [L-asparaginase] derived from _Escherichia coli_, a previously developed enzyme used for the treatment of acute lymphoblastic leukemia (ALL). However, using L-asparaginase derived from _Escherichia coli_ may cause hypersensitivity in some patients and require frequent administration. The pegylation of pegaspargase allows access to the enzyme's active sites while limiting reticuloendothelial system uptake and reducing immune detection, and it also increases the half-life of L-asparaginase.[A255912,A255917] In February 1994, pegaspargase was approved by the FDA for the treatment of ALL in patients with hypersensitivity to native forms of L-asparaginase.[A255927]

liquid

Pegaspargase is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of pediatric and adult patients with 1) first-line acute lymphoblastic leukemia or 2) acute lymphoblastic leukemia and hypersensitivity to asparaginase.[L44667]

Unlike normal cells, leukemia cells are dependent on an exogenous source of asparagine for survival. Pegaspargase hydrolyses asparagine into aspartic acid and ammonia, which depletes asparagine levels and leads to leukaemic cell death.[A255917] In patients given intramuscular doses of 2,500 International Units(IU)/m2 of pegaspargase, the serum levels of asparagine fall at day 4 and remain depleted for about 3 weeks. In adult patients with acute lymphocytic leukemia given 2,000 IU/m2 of pegaspargase intravenously, the deamination of asparagine takes place 2 h after administration and is sustained for 3 weeks, while in pediatric patients given 2,500 IU/m2, levels are sustained for 5 weeks.[A255927] The use of pegaspargase may lead to thrombosis, pancreatitis, glucose intolerance, hemorrhage, hepatotoxicity, anaphylaxis and serious hypersensitivity reactions.[L44667]

Pegaspargase is a pegylated L-asparaginase that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia. Asparagine is an amino acid that is vital for DNA and RNA synthesis and cell division. It is not an essential amino acid in humans since most normal human tissues can produce asparagine via the enzyme asparagine synthetase. However, leukemia cells have low levels of this enzyme and are unable to synthesize asparagine, making them dependent on exogenous sources. It has been suggested that pegaspargase kills leukemic cells by depleting plasma asparagine.[A103,A255912,L44667] Both _Escherichia coli_-derived L-asparaginase and pegaspargase follow the same mechanism of action; however, _Escherichia coli_-derived L-asparaginase requires frequent administration, presents a high incidence of hypersensitivity reactions, and can be neutralized without any signs of hypersensitivity. By pegylating L-asparaginase, the circulation time of L-asparaginase can be extended, and immunogenicity is reduced.[A255917]

In patients with acute lymphoblastic leukemia given 2,500 International Units (IU)/m2 of pegaspargase, the mean asparaginase Cmax was reached at approximately 1 IU/mL (n=45-52) five days after a single intramuscular injection. Pegaspargase had a relative bioavailability of 82% after the first intramuscular dose and 98% following repeat dosing. In patients given pegaspargase intravenously in a single infusion (n=47) during the induction phase, the mean Cmax and AUC0-inf were 1.6 IU/mL and 16.6 IU/mL⋅day, respectively.[L44667] The Tmax for these patients was 1.25 hr.[L44672] The impact of renal and hepatic impairment on pegaspargase pharmacokinetics is unknown.[L44667]

As a pegylated form of L-asparaginase, pegaspargase is expected to be metabolized by proteolytic enzymes throughout the body. Since these enzymes are ubiquitously distributed, the exact role of the liver is unknown.[L44672]

Patients that received 10,000 International Units/m2 of pegaspargase intravenously, had a slight increase in liver enzymes and a rash that developed 10 minutes after the start of the infusion, which was controlled with the administration of an antihistamine and by slowing down the infusion rate. There is no specific antidote for pegaspargase overdosage. The product label recommends to monitor patients closely for signs and symptoms of adverse reactions, and appropriately manage with symptomatic and supportive treatment in case of overdose. The carcinogenic, mutagenic and fertility effects of pegaspargase have not been evaluated.[L44667]

The mean elimination half-life of pegaspargase was approximately 5.8 days after a single intramuscular dose, and 5.3 days after a single intravenous dose.[L44667]

null

Due to its high molecular weight, pegaspargase is not excreted renally.[L44672]

Based on a non-compartmental analysis, pegaspargase has a steady-state volume of distribution of approximately 1.86 L/m2 after a single intramuscular injection and 2 L after a single intravenous infusion.[L44667]

For a single intramuscular and intravenous dose, the clearance of pegaspargase is 0.17 L/m2/day and 0.2 L/day, respectively.[L44667]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L01XX", "L01X", "L01", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "656.0", "description": "Oncaspar 750 unit/ml vial", "unit": "ml" } ]

[]

[ "Lyophilized Pegaspargase", "Lyophilized Pegaspargase", "Oncaspar", "Oncaspar", "Oncaspar", "Oncaspar", "Oncaspar", "Oncaspar", "Oncaspar" ]

[ "Oncaspar" ]

[]

[ "P05543" ]

[]

DB00060

Interferon beta-1a

Human interferon beta (166 residues), glycosylated, MW=22.5kD. It is produced by mammalian cells (Chinese Hamster Ovary cells) into which the human interferon beta gene has been introduced. The amino acid sequence is identical to that of natural human interferon beta.

liquid

For treatment of relapsing/remitting multiple sclerosis, also for condyloma acuminatum

Interferon beta upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Type I interferons also induce the synthesis of several key antiviral mediators including 2'-5' oligoadenylate synthetase (2'-5' A synthetase), beta-2 microglobulin and neopterin.

Interferon beta binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription) which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon beta binds more stably to type I interferon receptors than interferon alpha.

null

10 hrs

null

* 33-55 L/hour [Healthy SC injection of 60 mcg]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L03AB", "L03A", "L03", "L" ]

[]

[ { "cost": "247.79", "description": "Rebif 22 mcg/0.5 ml syringe", "unit": "syringe" }, { "cost": "247.79", "description": "Rebif 44 mcg/0.5 ml syringe", "unit": "syringe" }, { "cost": "781.8", "description": "Avonex admin pack 30 mcg vial", "unit": "vial" }, { "cost": "3252.29", "description": "Avonex 4 30 mcg/vial Kit 1 Box = 4 Vials ( 0.5ml Per Vial)", "unit": "box" }, { "cost": "3252.29", "description": "Avonex Prefilled (1 Box = 1 Kit = Four 30 mcg/0.5ml Syringes) Box", "unit": "box" } ]

[ { "approved": "2010-05-04", "country": "Canada", "expires": "2027-05-04", "number": "1341604" } ]

[ "Avonex", "Avonex", "Avonex", "Avonex", "Avonex", "Avonex", "Avonex", "Avonex", "Avonex", "Avonex", "Avonex", "Avonex", "Avonex", "Avonex Pen", "Rebif", "Rebif", "Rebif", "Rebif", "Rebif", "Rebif", "Rebif", "Rebif", "Rebif", "Rebif", "Rebif", "Rebif", "Rebif", "Rebif", "Rebif", "Rebif", "Rebif", "Rebif Rebidose", "Rebif Rebidose", "Rebif Rebidose", "Rebif Rebidose" ]

[ "Betaferon", "Blastoferon", "Uribeta" ]

[ "Avonex", "Avonex", "Avonex", "Rebif", "Rebif", "Rebif Rebidose", "Rebif Rebidose", "Rebif", "Avonex", "Rebif", "Rebif" ]

[ "P17181", "P48551" ]

[ "P05177" ]

[]

DB00061

Pegademase

Bovine adenosine deaminase derived from bovine intestine that has been extensively pegylated for extended serum half life.

liquid

For treatment of adenosine deaminase deficiency

Used to replace deficient or inactive adenosine deaminase which leads to severe combined immunodeficiency disease (SCID). The enzyme is responsible for converting adenosine to inosine. In the absence of adenosine deaminase, the purine substrates adenosine, 2'-deoxyadenosine and their metabolites are actually toxic to lymphocytes thereby leading to diminished immune function.

Pegademase converts adenosine (toxic) to inosine (less toxic) by deamination. It also converts 2'-deoxyadenosine to 2'-deoxyinosine via deamination.

Time to peak for plasma adenosine deaminase is 2 to 3 days

null

plasma adenosine deaminase elimination half-life is 3 to >6 days

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "L03AX", "L03A", "L03", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "4375.0", "description": "Adagen 250 unit/ml vial", "unit": "ml" } ]

[]

[ "Adagen" ]

[]

[ "P62993" ]

[]

DB00062

Albumin human

Human serum albumin is the primary protein present in human blood plasma. The main function of albumin is to maintain the oncotic pressure of blood [A33706]. It binds to water, cations (such as Ca2+, Na+ and K+), fatty acids, hormones, bilirubin, thyroxine (T4) and pharmaceuticals (including barbiturates). Albumin represents approximately 50% of the total protein content in healthy humans [A40060]. Human albumin is a small globular protein (molecular weight: 66.5 kDa), consisting of a single chain of 585 amino acids organized in three repeated homolog domains (sites I, II, and III). Each domain comprises two separate sub-domains (A and B) [A40060]. There are various preparations of albumin that are well established and widely available in the clinical setting [L3108], [L3109], [L3101]. Also known as _Albuminex_ 5% or 25%, one brand of human serum albumin is prepared from the pooled plasma of US donors in FDA-licensed facilities in the US [F229]. This is a biosimilar drug to existing human serum albumin and was approved for a biological license at both 5% and 25% concentrations by the FDA on June 21, 2018 [L3101].

solid

Albuminex solution is indicated for adults and children for hypovolemia, ascites, hypoalbuminemia including from burns, acute nephrosis, acute respiratory distress syndrome and cardipulmonary bypass [F229].

Serum albumin is a soluble, monomeric protein essential for maintaining and regulating the colloidal osmotic pressure of blood. It is utilized to increase the circulating plasma volume, which reduces hemoconcentration and blood viscosity. Albumin is also used as a transport protein that binds naturally occurring, therapeutic and toxic materials and drugs in the circulation [F229]. Human albumin makes up over 50% the total protein in the plasma and represents about 10% of protein synthesis activity by the liver. Human Albumin 25% has a corresponding hyper-oncotic effect [F230].

The main function of albumin results from its contribution to plasma colloid oncotic pressure and transport function [F230]. Albumin stabilizes circulating blood volume and carries hormones, enzymes, medicines, and toxins. Other physiological functions include antioxidant properties, free radical scavenging, in addition to maintenance capillary membrane integrity [F230]. Exogenously administered albumin increases the oncotic pressure of the intravascular system, moving fluids from the interstitial space, thereby decreasing edema and increasing the circulating blood volume. The increase in volume reduces the concentration and viscosity of blood in patients with decreased circulating blood volume while maintaining cardiac output in shock. In dehydrated patients, negligible effects exist on circulating blood volume. In addition to the above albumin replaces protein in patients with hypoproteinemia until the cause of the deficiency can be determined [L3104]. This drug has thousands of endogenous and exogenous targets. Human albumin also binds and carries a plethora of hydrophobic molecules, such as endogenous (i.e., cholesterol, fatty acids, bilirubin, thyroxine) or exogenous substances (for example, drugs and toxins), transition metal ions, as well as gas (nitric oxide [NO]), with resulting implications for their solubilisation, transport, metabolism, and detoxification [A40060].

null

In general, human albumin solutions are well-tolerated and no specific, clinically relevant alterations in organ function or coagulopathy have been substantiated [F229]. The most common adverse reactions are rigors, hypotension, tachycardia with increased heart rate, fever, chills, nausea, vomiting, dyspnea and/or bronchospasm, skin rash/pruritus. Stop the infusion immediately if anaphylaxis, with or without shock is observed [F229]. Hypervolemia may occur if the dosage and rate of infusion are not adjusted to the volume status of the patient. When clinical signs of cardiovascular overload occur (headache, dyspnea, jugular venous distention, increased blood pressure), the infusion must be slowed or stopped immediately [F230].

null

Albumin is distributed throughout the extracellular space and more than 60% of the body albumin pool is located in the extravascular fluid space [F230]. In healthy adults, less than 10% of infused albumin leaves the intravascular compartment during the first 2 hours following infusion of albumin. There is considerable individual variation in the effect of albumin on plasma volume, however [F229], [F230]. In some patients, the plasma volume can remain elevated for several hours. In critically ill patients, however, albumin can leak out of the vascular space in substantial amounts at an unpredictable rate that is difficult to predict [F230].

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "B05AA", "B05A", "B05", "B" ]

[ "Humans and other mammals" ]

[ { "cost": "1.32", "description": "Albutein 25% vial", "unit": "ml" }, { "cost": "1.97", "description": "Albumin 25% iv solution", "unit": "ml" }, { "cost": "2.22", "description": "Buminate 25% iv solution", "unit": "ml" }, { "cost": "0.3", "description": "Albumin (human) 5% iv solution", "unit": "ml" }, { "cost": "0.43", "description": "Albutein 5% iv solution", "unit": "ml" }, { "cost": "0.44", "description": "Buminate 5% iv solution", "unit": "ml" } ]

[ { "approved": "1996-09-24", "country": "United States", "expires": "2012-02-28", "number": "5558094" }, { "approved": "2004-04-20", "country": "United States", "expires": "2021-04-20", "number": "6723303" } ]

[ "Albuked", "Albuked", "Albuked", "Albuked", "Albuked", "Albuked", "Albuked", "Albumin (Human)", "Albumin (Human)", "Albumin (Human)", "Albumin (Human)", "Albumin (Human)", "Albumin (Human)", "Albumin (human) 25% Solution", "Albumin (human) 25% Solution USP", "Albumin (human) 5% Solution", "Albumin (human) 5% Solution, USP", "Albumin Human Diluent", "Albuminar-20", "Albuminar-25", "Albuminar-25", "Albuminar-5", "Albuminex", "Albuminex", "Albunex", "Alburex - 25", "Alburex - 5", "AlbuRx", "Alburx", "Albutein", "Albutein", "Albutein", "Albutein", "Albutein", "Albutein", "Albutein 25% Soln USP", "Albutein 5% Soln USP", "Beizray", "Buminate", "Buminate", "Buminate", "Buminate 25%", "Buminate 5%", "Diluent for Allergenic Extract Sterile Albumin Saline With Phenol", "Flexbumin", "Flexbumin", "Flexbumin", "Human Albumin Grifols", "Human Albumin Grifols", "Human Albumin Grifols 20%", "Humanalbin Inj 5%", "Kedbumin", "Macrotec", "Normal Serum Albumin Human 25% USP", "Octalbin 25%", "Octalbin 5%", "Optison", "Plasbumin", "Plasbumin", "Plasbumin", "Plasbumin", "Plasbumin", "Plasbumin", "Plasbumin-25", "Plasbumin-5", "Plasbumin-5 Inj 50mg/ml", "Plasmanate", "Sterile Diluent for Allergenic Extract", "Sterile Diluent for Allergenic Extract - Albumin Saline With Phenol", "Sterile Diluent for Allergenic Extracts Normal Saline With Hsa", "Venomil Honey Bee Venom (12mcg)", "Venomil Wasp Venom Protein (12mcg)", "Venomil White-faced Hornet Venom Protein (12mcg)", "Venomil Yellow Hornet Venom Protein (12mcg)", "Venomil Yellow Jacket Venom Protein (12mcg)" ]

[]

[ "Sterile Diluent for Allergenic Extract", "Macrotec", "Venomil Honey Bee Venom (12mcg)", "Venomil Wasp Venom Protein (12mcg)", "Venomil White-faced Hornet Venom Protein (12mcg)", "Venomil Yellow Hornet Venom Protein (12mcg)", "Venomil Yellow Jacket Venom Protein (12mcg)", "Albumin Human Diluent", "Beizray" ]

[]

DB00063

Eptifibatide

Synthetic cyclic hexapeptide that binds to platelet receptor glycoprotein and inhibits platelet aggregation. Derived from venom of the Southeastern pygmy rattlesnake (Sistrurus miliarus barbouri), eptifibatide is a cyclic heptapeptide that belongs to the class of arginin-glycin-aspartat-mimetics.

liquid

For treatment of myocardial infarction and acute coronary syndrome.

Eptifibatide is an anti-coagulant that selectively and reversibly blocks the platelet glycoprotein IIb/IIIa receptor.

Eptifibatide inhibits platelet aggregation by reversibly binding to the platelet receptor glycoprotein (GP) IIb/IIIa of human platelets, thus preventing the binding of fibrinogen, von Willebrand factor, and other adhesive ligands. Inhibition of platelet aggregation occurs in a dose- and concentration-dependent manner.

null

No major metabolites have been detected in human plasma. Deamidated eptifibatide and other, more polar metabolites have been detected in urine.

Eptifibatide was not lethal to rats, rabbits, or monkeys when administered by continuous intravenous infusion for 90 minutes at a total dose of 45 mg/kg (about 2 to 5 times the recommended maximum daily human dose on a body surface area basis)

Approximately 2.5 hours

Approximately 25%

null

* 55 mL/kg/h [patients with coronary artery disease]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "B01AC", "B01A", "B01", "B" ]

[ "Humans and other mammals" ]

[ { "cost": "3.88", "description": "Integrilin 75 mg/100 ml vial", "unit": "ml" }, { "cost": "10.74", "description": "Integrilin 200 mg/100 ml vial", "unit": "ml" }, { "cost": "12.41", "description": "Integrilin 20 mg/10 ml vial", "unit": "ml" } ]

[ { "approved": "1997-11-11", "country": "United States", "expires": "2014-11-11", "number": "5686570" }, { "approved": "2007-04-17", "country": "Canada", "expires": "2013-04-27", "number": "2133205" }, { "approved": "1998-09-15", "country": "United States", "expires": "2015-09-15", "number": "5807825" } ]

[ "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide", "Eptifibatide Accord", "Eptifibatide Accord", "Eptifibatide Injection", "Eptifibatide Injection", "Eptifibatide Injection", "Eptifibatide Injection", "Eptifibatide Injection", "Eptifibatide Injection", "Eptifibatide Injection", "Eptifibatide Injection", "Eptifibatide Injection", "Eptifibatide Injection", "Eptifibatide Injection", "Eptifibatide Injection", "Integrilin", "Integrilin", "Integrilin", "Integrilin", "Integrilin", "Integrilin" ]

[]

[ "P05106", "P08514", "A0A024R8I1", "Q00975" ]

[]

DB00065

Infliximab

Infliximab is a tumor necrosis factor (TNF-alpha or TNF-α) blocker and a chimeric monoclonal IgG1 antibody composed of human constant (75%) and murine variable (25%) regions [A31469]. Infliximab is produced by a recombinant cell line cultured by continuous perfusion. Tumor necrosis factor-alpha (TNF-α) is a key proinflammatory cytokine involved in chronic inflammatory diseases [A31469]. Its hyperactivity and enhanced signalling pathways can be observed in inflammatory diseases where it activates further pro-inflammatory cascades. By binding to both the soluble subunit and the membrane-bound precursor of TNF-α [A106], infliximab disrupts the interaction of TNF-α with its receptors and may also cause lysis of cells that produce TNF-α [A106]. Infliximab was first approved by the FDA in 1998 under the market name Remicade as an intravenous injection. It is indicated for the treatment of various inflammatory disorders such as adult or pediatric Chron's disease, adult or pediatric ulcerative colitis, rheumatoid arthritis in combination with methotrexate, ankylosing spondyliti, psoriatic arthritis, and plaque psoriasis [FDA Label]. In clinical trials, multiple infusions of infliximab displayed in a reduction of signs and symptoms of inflammatory diseases and induction of remission in patients who have had an inadequate response to alternative first-line therapies for that disorder [FDA Label]. There are currently two biosilimars of infliximab available in the US market that demonstrate a high degree of similarity to the reference product, Remicade. They are approved for all eligible indications of the reference product. Inflectra, a first biosimilar drug product, was approved in 2016. In December 2017, Ixifi, a second biosimilar that was developed by Pfizer, was granted approval by the FDA.

liquid

Infliximab is indicated for the following conditions: - moderately to severely active ulcerative colitis following treatment with an infliximab product administered intravenously [L51793] - moderately to severely active Crohn’s disease following treatment with an infliximab product administered intravenously [L51793] - use in combination with methotrexate for the reduction in signs and symptoms, inhibition of the progression of structural damage and improvement in physical function in adult patients with moderately to severely active rheumatoid arthritis. • maintenance treatment of adults with moderately to severely active Crohn’s disease who have had an inadequate response or were intolerant to conventional therapy. Remsima SC should only be used as maintenance therapy after the completion of an induction period with intravenous infliximab. • maintenance treatment of adults with moderately to severely active ulcerative colitis who have had an inadequate response or were intolerant to conventional therapy. Remsima SC should only be used as maintenance therapy after the completion of an induction period with intravenous infliximab.

Infliximab disrupts the activation of pro-inflammaory cascade signalling. Infliximab has shown to reduce infiltration of inflammatory cells into sites of inflammation. It also attenautes the expression of molecules mediating cellular adhesion {including E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)}, chemoattraction {[IL-8 and monocyte chemotactic protein (MCP-1)} and tissue degradation {matrix metalloproteinase (MMP) 1 and 3} [FDA Label].

Infliximab is a IgG1κ monoclonal antibody that binds to soluble and transmembrane forms of TNF-α with high affinity to disrupt the pro-inflammatory cascade signalling. Binding of the antibody to TNF-α prevents TNF-α from interacting with its receptors. Infliximab does not neutralize TNF-β (lymphotoxin-α), a related cytokine that utilizes the same receptors as TNF-α [FDA Label]. Blocked actions of TNF-α further leads to downregulation of local and systemic pro-inflammatory cytokines (i.e. IL-1, IL-6), reduction of lymphocyte and leukocyte migration to sites of inflammation, induction of apoptosis of TNF-producing cells (i.e. activated monocytes and T lymphocytes), increased levels of nuclear factor-κB inhibitor, and reduction of reduction of endothelial adhesion molecules and acute phase proteins [A31469]. Its inhibitory actions on TNF-α was demonstrated in human fibroblasts, endothelial cells, neutrophils, B and Tlymphocytes and epithelial cells [FDA Label]. Infliximab also atteunates the production of tissue degrading enzymes synthesized by synoviocytes and/or chondrocytes. According to a transgenic mice study that developed polyarthritis due to consitutive levels of human TNF-α, infliximab decreased synovitis and joint erosions in collagen-induced arthritis and allows eroded joints to heal [FDA Label].

Following a single intravenous infusion, infliximab absorption displays a linear relationship between the dose administered and the maximum serum concentration [FDA Label]. In patients with Crohn's disease, the maximum plasma concentration (Cmax) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 75 µg/mL and 181 µg/mL, respectively. In a maintenance therapy study, multiple infusions of infliximab (at week 0, 2 and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in Cmax of 120 µg/mL and 189 µg/mL , respectively [A31469]. In patients with rheumatoid arthritis, the Cmax of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 192±51 µg/mL, 427±106 µg/mL, and 907±183 µg/mL, respectively [A31469].

null

The median terminal half-life of infliximab is 7.7 to 9.5 days. The data is based on a pharmacokinetic study in patients with Crohn's disease, plaque psoriasis and rheumatoid arthritis receiving a single dose of infliximab [FDA Label].

null

Therapeutic monoclonal antibodies including infliximab are predicted to be nonspecifically metabolized to peptides and amino acids that can be re-used in the body for de novo synthesis of proteins or arc excreted by the kidney [A19126]. The reticuloendothelial system (RES) are phagocytic cells of the immune system such as macrophages and monocytes that play a role in the elimination of endogenous IgG antibodies. Although administered infliximab accounts for a small fraction of total endogenous IgG and this route is not likely saturated by therapeutic mAbs, infliximab may be removed by opsonization via RES following binding of the Fc part of the antibody to Fcy-receptors expressed on the RES [A19126].

Based on a pharmacokinetic study of adult patients, the distribution at steady state was independent of dose and indicated that infliximab was distributed primarily within the vascular compartment [FDA Label]. In patients with Crohn's disease, the apparent volume of distribution at steady state (Vss) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 80 mL/kg and 65 mL/kg, respectively. In a maintenance therapy study, multiple infusions of infliximab (at week 0, 2 and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in Vss of 70 mL/kg and 81 mL/kg , respectively [A31469]. In patients with rheumatoid arthritis, the Vss of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 4.3±2.5 L, 3.2±0.7 L, and 3.1±0.6 L, respectively [A31469].

In patients with Crohn's disease, the total body clearance (CL) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 18.4 mL/h and 14.3 mL/h, respectively. In a maintenance therapy study, multiple infusions of infliximab (at week 0, 2 and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in CL of 15.2 mL/h and 15.2 mL/h, respectively [A31469]. In patients with rheumatoid arthritis, the CL of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 11±7.5 mL/h, 11.4±5 mL/h, and 11±8.9 mL/h, respectively [A31469]. Development of antibodies to infliximab increased infliximab clearance [FDA Label].

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "L04AB", "L04A", "L04", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "789.44", "description": "Remicade 100 mg vial", "unit": "vial" }, { "cost": "821.02", "description": "Remicade 100 mg Solution Vial", "unit": "vial" } ]

[ { "approved": "2001-02-06", "country": "Canada", "expires": "2012-03-18", "number": "2106299" } ]

[ "Avsola", "Avsola", "Flixabi", "Flixabi", "Flixabi", "Flixabi", "Flixabi", "Inflectra", "Inflectra", "Inflectra", "Inflectra", "Inflectra", "Inflectra", "Inflectra", "Infliximab", "Ixifi", "Omvyence", "Remicade", "Remicade", "Remicade", "Remicade", "Remicade", "Remicade", "Remicade", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima", "Remsima Sc", "Remsima Sc", "Renflexis", "Renflexis", "Renflexis", "Zessly", "Zessly", "Zessly", "Zessly", "Zessly", "Zymfentra", "Zymfentra" ]

[ "Avsola" ]

[]

[ "P01375" ]

[]

DB00066

Follitropin

Follitropin is a human follicle stimulating hormone (FSH) preparation of recombinant DNA origin, which consists of two non-covalently linked, non-identical glycoproteins designated as the alpha- and beta- subunits. The alpha- and beta- subunits have 92 and 111 amino acids. The alpha subunit is glycosylated at Asn 51 and Asn 78 while the beta subunit is glycosylated at Asn 7 and Asn 24. Follitropin beta is produced in genetically engineered Chinese hamster cell lines (CHO). The nomenclature “beta” differentiates it from another recombinant human FSH product that was marketed earlier as follitropin alpha. Follitropin is important in the development of follicles produced by the ovaries. Given by subcutaneous injection, it is used in combination with human chorionic gonadotropin (hCG) to assist in ovulation and fertility. Follitropin may also be used to cause the ovary to produce several follicles, which can then be harvested for use in gamete intrafallopian transfer (GIFT) or in vitro fertilization (IVF). Numerous physio-chemical tests and bioassays indicate that follitropin beta and follitropin alpha are indistinguishable. However, a more recent study showed there is may be a slight clinical difference, with the alpha form tending towards a higher pregnancy rate and the beta form tending towards a lower pregnancy rate, but with significantly higher estradiol (E2) levels. Structural analysis shows that the amino acid sequence of follitropin beta is identical to that of natural human follicle stimulating hormone (FSH). Further, the ogliosaccharide side chains are very similar, but not completely identical to that of natural FSH. However, these small differences do not affect the bioactivity compared to natural FSH.

liquid

In women having been diagnosed with primary ovarian failure, it is used in combination with human chorionic gonadotropin (hCG) to assist in ovulation and fertility. In men with hypogonadotrophic hypogonadism, it is used to induce spermatogenesis. Follitropin may also be used to cause the ovary to produce several follicles, which can then be harvested for use in gamete intrafallopian transfer (GIFT) or in vitro fertilization (IVF).

Used for the treatment of female infertility, Follitropin beta or follicle stimulating hormone (FSH) stimulates ovarian follicular growth in women who do not have primary ovarian failure. FSH, the active component of Follitropin beta is the primary hormone responsible for follicular recruitment and development.

Follitropin is a recombinant form of endogenous follicle stimulating hormone (FSH). FSH binds to the follicle stimulating hormone receptor which is a G-coupled transmembrane receptor. Binding of the FSH to its receptor seems to induce phosphorylation and activation of the PI3K (Phosphatidylinositol-3-kinase) and Akt signaling pathway, which is known to regulate many other metabolic and related survival/maturation functions in cells.

The absorption rate is the main driving force behind the pharmokinetics of Follitropin alpha as the rate of absorption was found to be slower than the elimination rate after administration subcutaneously and intramuscularly. The bioavailability is approximately 66-76%. The time to peak after subcutaneous injection in healthy volunteers was 8-16 hours in females and 11-20 hours in males.

null

Headaches, ovarian cysts, nausea and upper respiratory tract infections occurred in more than 10% of women in clinical trials. In men, the most serious adverse events reported were testicular surgery for cryptorchidism which existed prestudy, hemoptysis, an infected pilonidal cyst, and lymphadenopathy associated with an Epstein-Barr viral infection. Other concerns include overstimulation of the ovaries, pulmonary and vascular complications and multiple births. Post-marketing reports revealed hypersensitivity reactions including anaphylactoid reactions and asthma. Follitropin is contraindicated in pregnant women. No studies have been done in nursing mothers.

Circulation half life of 3-4 hours, elimination half life of 35-40 hours

null

Via liver and kidneys.

* 8 L [female subjects following intravenous administration of a 300 IU dose]

* 0.01 1*h-1kg-1 [European women with a single intramuscular dose of 300 IU] * 0.01 1*h-1kg-1 [Japanese women with a single intramuscular dose of 300 IU]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "G03GA", "G03G", "G03", "G", "G03GA", "G03G", "G03", "G", "G03GA", "G03G", "G03", "G" ]

[ "Humans and other mammals" ]

[ { "cost": "109.51", "description": "Follistim aq 75 unit vial", "unit": "vial" }, { "cost": "117.47", "description": "Gonal-f rff 75 unit vial", "unit": "vial" }, { "cost": "219.02", "description": "Follistim aq 150 unit vial", "unit": "vial" }, { "cost": "438.05", "description": "Follistim aq 300 unit cartridge", "unit": "cartridge" }, { "cost": "455.57", "description": "Follistim AQ 300unt/0.36ml Solution 0.42ml Cartridge", "unit": "cartridge" }, { "cost": "469.87", "description": "Gonal-f rff 300 unit pen", "unit": "pen" }, { "cost": "704.81", "description": "Gonal-f rff 450 unit pen", "unit": "pen" }, { "cost": "733.0", "description": "Gonal-f 450 unit Solution Vial", "unit": "vial" }, { "cost": "911.14", "description": "Follistim AQ 600unt/0.72ml Solution 0.78ml Cartridge", "unit": "cartridge" }, { "cost": "1366.71", "description": "Follistim AQ 900unt/1.08ml Solution 1 Cartridge = 1.17ml", "unit": "cartridge" }, { "cost": "1409.62", "description": "Gonal-f rff 900 unit pen", "unit": "ml" } ]

[ { "approved": "1993-12-14", "country": "United States", "expires": "2011-03-20", "number": "5270057" }, { "approved": "2003-10-21", "country": "Canada", "expires": "2011-03-08", "number": "2037884" }, { "approved": "2009-07-21", "country": "United States", "expires": "2019-08-23", "number": "7563763" }, { "approved": "1999-07-27", "country": "United States", "expires": "2018-01-14", "number": "5929028" }, { "approved": "2008-11-04", "country": "United States", "expires": "2019-08-23", "number": "7446090" }, { "approved": "2010-06-22", "country": "United States", "expires": "2024-04-02", "number": "7741268" } ]

[ "Bemfola", "Bemfola", "Bemfola", "Bemfola", "Bemfola", "Bemfola", "Bemfola", "Bemfola", "Bemfola", "Bemfola", "Bemfola", "Bemfola", "Bemfola", "Bemfola", "Bemfola Needles", "Bravelle", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Fertavid", "Follistim", "Follistim AQ", "Follistim AQ", "Follistim AQ", "Follistim AQ", "Follistim AQ", "Follistim AQ", "Follistim AQ", "Follistim AQ", "Follistim AQ", "Gonal-f", "Gonal-f", "Gonal-f", "Gonal-f", "Gonal-f", "Gonal-f", "Gonal-f", "Gonal-f", "Gonal-f", "Gonal-F", "Gonal-F", "Gonal-F", "Gonal-F", "Gonal-F", "Gonal-F", "Gonal-F", "Gonal-F", "Gonal-F", "Gonal-F", "Gonal-F", "Gonal-F Pen", "Gonal-F Pen", "Gonal-F Pen", "Gonal-F Rff", "Gonal-F Rff", "Gonal-f RFF Pen", "Gonal-f RFF Pen", "Gonal-f RFF Pen", "Gonal-f RFF Redi-ject", "Gonal-f RFF Redi-ject", "Gonal-f RFF Redi-ject", "Gonal-f RFF Redi-ject", "Humegon Inj 75 I.U.", "Menopur", "Ovaleap", "Ovaleap", "Ovaleap", "Pergonal 75 I.U.", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon", "Puregon (600 Iu)", "Puregon 100 I.U.", "Puregon 50 I.U.", "Rekovelle", "Rekovelle", "Rekovelle", "Rekovelle", "Rekovelle", "Rekovelle", "Rekovelle", "Rekovelle", "Rekovelle", "Rekovelle", "Rekovelle", "Rekovelle", "Repronex" ]

[ "Cinnal-F" ]

[ "Follistim", "Repronex", "Menopur", "Humegon Inj 75 I.U.", "Pergonal 75 I.U.", "Puregon 50 I.U.", "Puregon 100 I.U.", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris", "Pergoveris" ]

[ "P23945" ]

[]

DB00067

Vasopressin

Vasopressin (arginine-vasopressin or antidiuretic hormone) is a nonapeptide primarily produced in the hypothalamus that exhibits diverse physiological functions related to diuresis, hemodynamic modulation, and behaviour.[A110, A111, A112, A113, A228008] Vasopressin is very similar to oxytocin, differing in the third and eighth amino acids.[A228013] Despite a wide variety of functions, exogenous vasopressin is primarily used to control blood pressure during systemic shock by increasing vasoconstriction and renal fluid reuptake by acting through V1 and V2 cellular receptors.[A228008, A228013, A228018, L31413] The vasopressive effect of posterior pituitary gland extracts was noted in 1895, while vasopressin itself was not purified until 1951. It has been used for more than five decades for varying conditions, including variceal bleeding, diabetes insipidus, and, more recently, vasodilatory shock.[A228013] It is currently marketed under the trademark VASOSTRICT® by PAR Pharmaceuticals.[L31413]

solid

Vasopressin is indicated to increase blood pressure in adults in vasodilatory shock refractory to the application of fluids and catecholamines.[L31413]

Vasopressin is a nonapeptide antidiuretic hormone involved in modulating various physiological processes, including autonomic signalling, stress response, behaviour, and memory; the most well-known modulation is of blood pressure.[A110, A111, A112, A113, L31413] Vasopressin acts both within the brain and in the periphery to modulate blood pressure through sympathetic outflow, baroreflex modulation, vasoconstriction, and renal fluid retention.[A228008, A228013, A228018] These mechanisms vary by location and physiological state, leading to occasionally contradictory responses to vasopressin. Although generally safe, vasopressin may worsen cardiac output in patients with impaired cardiac function. The cessation of vasopressin therapy may result in transient reversible diabetes insipidus, which may require additional desmopressin or vasopressin to manage.[L31413]

Vasopressin, Cyclo (1-6) L-Cysteinyl-L-Tyrosyl-L-PhenylalanylL-Glutaminyl-L-Asparaginyl-L-Cysteinyl-L-Prolyl-L-Arginyl-L-Glycinamide, is a cyclic nonapeptide hormone primarily produced by the supraoptic and periventricular nuclei of the hypothalamus.[A228008, L31413] Vasopressin release is mediated by sensory pathways, in which either a 2% increase in plasma osmolarity or a 10% decrease in blood pressure causes the release of endogenous vasopressin.[A228013] Upon release, vasopressin mediates a variety of physiological effects, both centrally and systemically, primarily by binding to G-protein-coupled receptors termed V1 (V1A), V2, and V3 (V1B). V1 receptors are abundantly expressed in the brain whereby vasopressin binding can increase blood pressure through autonomic pathways.[A228008] Peripherally, V1 is localized in the blood vessels (vascular smooth muscle), platelets, adrenal glands, kidneys, and liver.[A228008, A228018] Vasopressin binding to V1 causes hydrolysis of phosphatidylinositol-4,5-bisphosphate into inositol triphosphate (IP3) and diacylglycerol (DAG) by phospholipase C, which in turn release intracellular calcium and activate protein kinase C (PKC) to open voltage-gated calcium channels (VGCCs) while closing potassium channels. Overall, intracellular calcium levels rise, which bind calmodulin and cause muscular contraction, resulting in vasoconstriction.[A228013] This is balanced by the apparent ability of vasopressin to induce vasodilation through binding oxytocin receptors and activating endothelial nitric oxide (NO) synthase; NO acts antagonistically to reduce muscle contraction.[A228013] It is also thought that vasopressin, acting through both V1 and oxytocin receptors, causes the cardiac release of atrial natriuretic peptide (ANP), which has a negative inotropic effect; indeed, vasopressin tends to decrease heart rate and cardiac output, although the opposite effect has been noted with low doses.[A228013, L31413] V2 receptors are abundantly expressed in the distal convoluted tubules and the collecting ducts of the kidneys.[A228018, A228023] Vasopressin binding to V2 causes activation of a Gs protein that subsequently activates protein kinase A (PKA) through adenylyl cyclase-mediated increase in cyclic adenosine monophosphate (cAMP), which leads to phosphorylation of the water channel aquaporin-2 (AQP2) and its trafficking to the cell surface.[A228018, A228023] Increased AQP2 levels lead to increased water reabsorption and explains vasopressin's antidiuretic effects.[A228018] V3 (formerly V1B) receptors are primarily located in the anterior pituitary and brain.[A228008, A228018] Vasopressin released during acute stress causes adrenocorticotropic hormone (ACTH) release from the pituitary through V3 and by potentiating the effects of corticotrophin-releasing factor. Within the brain itself, V3 activation modulates various effects, including recognition, memory, aggression, anxiety, and depression.[A228008] Thus, vasopressin can affect a wide variety of physiological processes, often in apparently contradictory ways depending on the patient's dose and physiological state. Vasodilatory shock causes an immediate release of vasopressin from 20 to 200 times its normal serum concentration, which falls again to normal levels in prolonged shock; in this context, normal serum levels are insufficient to control the pathologic vasodilation.[A228013, A228018] In these cases, vasopressin acts to depolarize hyperpolarized vascular smooth muscle cells, restore sensitivity to catecholamines, and inhibit excessive nitric oxide production, primarily through acting through V1 receptors. Therefore, vasopressin helps decrease the dose requirement for norepinephrine and is routinely administered together with norepinephrine to restore normal blood pressure in shock states.[A228018, L31413]

null

Animal studies suggest that vasopressin is metabolized by serine proteases, carboxypeptidases, and disulphide oxidoreductases, primarily in the liver and kidneys. These cleavage events occur at sites important for vasopressin's activity, and hence the metabolites are expected to be inactive.[L31413]

Vasopressin overdose is expected to present with consequences related to excessive vasoconstriction of peripheral, mesenteric, coronary vascular beds, hyponatremia, and possibly with ventricular tachyarrhythmias, rhabdomyolysis, and gastrointestinal symptoms. As vasopressin is rapidly metabolized and cleared, symptoms will resolve with cessation of vasopressin administration.[L31413]

Vasopressin administered at 0.01-0.1 U/min has an apparent t1/2 of ≤10 minutes,[L31413] although half-lives of up to 44 minutes have been reported in the literature.

null

Vasopressin is primarily eliminated in the urine, where only 6% of the dose is excreted unchanged.[L31413]

null

Vasopressin has a clearance of 9-25 mL/min/kg in patients with vasodilatory shock receiving 0.01-0.1 U/min of vasopressin.[L31413]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[]

[ "Humans and other mammals" ]

[ { "cost": "1.86", "description": "Vasopressin 20 unit/ml vial", "unit": "ml" }, { "cost": "2.88", "description": "Vasopressin 10 unit/0.5 ml vial", "unit": "vial" }, { "cost": "7.68", "description": "Pitressin 20 unit/ml vial", "unit": "ml" } ]

[ { "approved": "2017-06-27", "country": "United States", "expires": "2035-01-30", "number": "9687526" }, { "approved": "2016-06-28", "country": "United States", "expires": "2035-01-30", "number": "9375478" }, { "approved": "2017-08-29", "country": "United States", "expires": "2035-01-30", "number": "9744209" }, { "approved": "2017-08-29", "country": "United States", "expires": "2035-01-30", "number": "9744239" }, { "approved": "2017-09-05", "country": "United States", "expires": "2035-01-30", "number": "9750785" }, { "approved": "2018-04-10", "country": "United States", "expires": "2035-01-30", "number": "9937223" }, { "approved": "2018-07-03", "country": "United States", "expires": "2035-01-30", "number": "10010575" }, { "approved": "2018-03-27", "country": "United States", "expires": "2035-01-30", "number": "9925233" }, { "approved": "2018-05-22", "country": "United States", "expires": "2035-01-30", "number": "9974827" }, { "approved": "2018-05-15", "country": "United States", "expires": "2035-01-30", "number": "9968649" }, { "approved": "2018-05-08", "country": "United States", "expires": "2035-01-30", "number": "9962422" }, { "approved": "2018-03-27", "country": "United States", "expires": "2035-01-30", "number": "9925234" }, { "approved": "2018-05-29", "country": "United States", "expires": "2035-01-30", "number": "9981006" }, { "approved": "2018-03-20", "country": "United States", "expires": "2035-01-30", "number": "9919026" } ]

[ "Pitressin", "Pitressin", "Pitressin", "Pitressin Inj 10 Unit/0.5ml", "Pressyn Ar", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin", "Vasopressin in 0.9% Sodium Chloride", "Vasopressin in 0.9% Sodium Chloride", "Vasopressin in 0.9% Sodium Chloride", "Vasopressin in 0.9% Sodium Chloride", "Vasopressin in 0.9% Sodium Chloride", "Vasopressin Inj 20unit/ml USP", "Vasopressin Inj 20unit/ml USP", "Vasopressin Injection USP", "Vasopressin Injection, USP", "Vasostrict", "Vasostrict", "Vasostrict", "Vasostrict", "Vasostrict", "Vasostrict", "Vasostrict", "Vasostrict" ]

[]

[ "P30518", "P37288", "P47901", "P30559" ]

[]

[ "Q92887" ]

DB00068

Interferon beta-1b

Human interferon beta (165 residues), cysteine 17 is substituted with serine. Produced in E. coli, no carbohydrates, MW=18.5kD

liquid

Interferon beta-1b is a drug used for the treatment of relapsing/remitting multiple sclerosis. It has been shown to slow the advance of the disease as well as to decrease the frequency of attacks.

Interferon beta upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Type I interferons also induce the synthesis of several key antiviral mediators including 2'-5' oligoadenylate synthetase (2'-5' A synthetase), beta-2 microglobulin, neopterin and protein kinase R.

Interferon beta binds to type I interferon receptors (IFNAR1 and IFNAR2c) which activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon beta binds more stably to type I interferon receptors than interferon alpha.

null

* 0.25 to 2,88 L/kg

* 9.4 – 28.9 mL/min•kg-1 [patients with diseases other than MS receiving single intravenous doses up to 2.0 mg]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "L03AB", "L03A", "L03", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "196.76", "description": "Extavia 0.3 mg kit", "unit": "kit" }, { "cost": "227.69", "description": "Betaseron 0.3 mg kit", "unit": "kit" }, { "cost": "3315.06", "description": "Betaseron 14 0.3 mg Solution 1 Box Contains Fourteen .3 mg Vials.", "unit": "box" } ]

[ { "approved": "1999-12-28", "country": "Canada", "expires": "2016-12-28", "number": "1340861" }, { "approved": "1998-03-10", "country": "Canada", "expires": "2015-03-10", "number": "1339707" } ]

[ "Betaferon", "Betaferon", "Betaferon", "Betaferon", "Betaferon", "Betaferon", "Betaferon", "Betaferon", "Betaferon", "Betaferon", "Betaseron", "Betaseron", "Betaseron", "Extavia", "Extavia", "Extavia", "Extavia", "Extavia", "Extavia", "Extavia", "Extavia", "Extavia" ]

[]

[ "P17181", "P48551" ]

[ "P05177" ]

[]

DB00069

Interferon alfacon-1

Interferon alfacon-1 is a recombinant non-naturally occurring type-I interferon. The 166-amino acid sequence of Interferon alfacon-1 was derived by scanning the sequences of several natural interferon alpha subtypes and assigning the most frequently observed amino acid in each corresponding position. Four additional amino acid changes were made to facilitate the molecular construction, and a corresponding synthetic DNA sequence was constructed using chemical synthesis methodology. Interferon alfacon-1 differs from interferon alfa-2b at 20/166 amino acids (88% homology), and comparison with interferon-beta shows identity at over 30% of the amino acid positions. Interferon alfacon-1 is produced in Escherichia coli (E. coli) cells that have been genetically altered by insertion of a synthetically constructed sequence that codes for Interferon alfacon-1. Prior to final purification, Interferon alfacon-1 is allowed to oxidize to its native state, and its final purity is achieved by sequential passage over a series of chromatography columns. This protein has a molecular weight of 19,434 daltons.

liquid

For the treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma

Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R.

Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription) which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. The resulting actions include gene transcription, inhibition of cellular growth, alteration of the state of cellular differentiation, interference with oncogene expression, alteration of cell surface antigen expression, increasing phagocytic activity of macrophages, and augmentation of the cytotoxicity of lymphocytes for target cells.

Subcutaneous bioavailability averages 99% in golden Syrian hamsters and 83% to 104% in rhesus monkeys.

null

Reproductive toxicity studies in pregnant rhesus monkeys and golden Syrian hamsters demonstrated an increase in fetal loss in hamsters treated with Interferon alfacon-1 at doses of > 150 mcg/kg/day, and in rhesus monkeys at doses of 3 and 10 mcg/kg/day. The Interferon alfacon-1 toxicity profile described is consistent with the known toxicity profile of other alpha interferons.

The terminal half-life following subcutaneous dosing was 1.3 hours in golden Syrian hamsters and 3.4 hours in rhesus monkeys.

null

Due predominantly to catabolism and excretion by the kidneys.

null

Clearance, averaging 1.99 mL/minute/kg in golden Syrian hamsters and 0.71 to 0.92 mL/minute/kg in rhesus monkeys

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L03AB", "L03A", "L03", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "129.08", "description": "Infergen 9 mcg/0.3 ml vial", "unit": "vial" }, { "cost": "134.24", "description": "Infergen 15 mcg/0.5ml Injectable 0.5ml Vial", "unit": "vial" } ]

[]

[ "Infergen", "Infergen", "Infergen", "Infergen" ]

[ "Advaferon" ]

[]

[ "P17181", "P48551" ]

[ "P05177" ]

[]

DB00070

Hyaluronidase (ovine)

Highly purified sheep hyaluronidase for administration by injection into the vitreous of the eye.

liquid

For increase of absorption and distribution of other injected drugs and for rehydration.

Hyaluronidase hydrolyzes hyaluronic acid and increase diffusion of injected drugs, thus facilitating their absorption. Hyaluronidase is used for enhancing absorption and distribution of other injected drugs.

Hyaluronidase is a spreading or diffusing substance. It increase the permeability of connective tissue through the hydrolysis of hyaluronic acid. Hyaluronidase hydrolyzes hyaluronic acid by splitting the glucosaminidic bond between C1 of the glucosamine moiety and C4 of glucuronic acid. This temporarily decreases the viscosity of the cellular cement and increases diffusion of injected fluids or of localized transudates or exudates, thus facilitating their absorption.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[]

[ "Humans and other mammals" ]

[ { "cost": "108.0", "description": "Hylenex 150 unit/ml vial", "unit": "ml" }, { "cost": "900.0", "description": "Hyaluronidase powder", "unit": "g" }, { "cost": "967.2", "description": "Vitrase 6200 unit vial", "unit": "vial" }, { "cost": "19200.0", "description": "Vitrasert 4.5 mg implant", "unit": "implant" } ]

[]

[ "Vitrase", "Vitrase", "Vitrase" ]

[ "Diffusin", "Enzodase", "Hyazyme", "Wydase" ]

[]

[ "P01137" ]

[]

[ "P02768" ]

[]

DB00071

Insulin pork

Insulin isolated from pig pancreas. Composed of alpha and beta chains, processed from pro-insulin. Forms a hexameric structure.

liquid

For the treatment of type I and II diabetes mellitus.

Insulin is used in the treatment of type I and type II diabetes. The primary activity of insulin is the regulation of glucose metabolism. In muscle and other tissues (except the brain), insulin causes rapid transport of glucose and amino acids intracellularly. It also promotes anabolism, and inhibits protein catabolism. In the liver, insulin promotes the uptake and storage of glucose in the form of glycogen, inhibits gluconeogenesis, and promotes the conversion of excess glucose into fat.

Insulin binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism.

null

Insulin is predominantly cleared by metabolic degradation via a receptor-mediated process.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "A10AC", "A10A", "A10", "A", "A10AB", "A10A", "A10", "A", "A10AE", "A10A", "A10", "A", "A10AD", "A10A", "A10", "A" ]

[ "Humans and other mammals" ]

[]

[ "Hypurin Nph Insulin Isophane Pork", "Hypurin Regular Insulin Pork", "Regular Purified Pork Insulin Inj" ]

[]

[ "P06213", "P08069" ]

[ "P05177", "P14735" ]

[]

DB00072

Trastuzumab

Produced in CHO cell cultures, trastuzumab is a recombinant IgG1 kappa, humanized monoclonal antibody [A40276] that selectively binds with high affinity in a cell-based assay (Kd = 5 nM) to the extracellular domain of the human epidermal growth factor receptor protein (HER2).[L14015] It is used as a treatment of human epidermal growth factor receptor (HER)-2+ metastatic breast cancer, where there is a proven amplification of the HER-2 oncogene or over-expression of the HER-2 protein in tumours. It is suggested that the overexpression or gene amplification of HER2 has been found in about 20–30% of breast cancers and elevated activation of HER2 triggers multiple downstream pathways leading to abnormal proliferation of cancer cells [A121]. Trastuzumab binds to HER2 and suppresses cancer cell growth, proliferation, and survival directly and indirectly [A121]. In December 2017, FDA approved OGIVRI (trastuzumab-dkst) as a biosimilar to Herceptin (trastuzumab) for the treatment of patients with breast or metastatic stomach cancer (gastric or gastroesophageal junction adenocarcinoma) whose tumors overexpress the HER2 gene (HER2+). It displays biosimilar properties as Herceptin according to clinical data. While Ogivri is the first biosimilar approved in the U.S. for the treatment of breast cancer or stomach cancer, it is the second biosimilar approved in the U.S. for the treatment of cancer. Herzuma (trastuzumab-pkrb) is a biosimilar drug approved in December 2018 for the treatment of HER2-overexpressing breast cancer. KANJINTI (trastuzumab-anns) is another biosimilar approved by the FDA in June 2019.[L14135] ONTRUZANT, another biosimilar of Herceptin, was approved by Health Canada in February 2022.[L40303, L40308] In November 2023, trastuzumab was also approved by the EMA under the brand name Herwenda.[L49339]

solid

For the adjuvant treatment of HER2-overexpressing breast cancer, trastuzumab is indicated in several clinical settings: as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; as part of a treatment regimen with docetaxel and carboplatin; or as monotherapy following multi-modality anthracycline-based therapy.[L14015] Trastuzumab is indicated as a first-line treatment, in combination with paclitaxel, for metastatic HER2-overexpressing breast cancer, and as monotherapy in patients who have previously received one or more chemotherapy regimens in the metastatic setting.[L14015] In Europe, trastuzumab can also be used in combination with paclitaxel or docetaxel for the treatment of metastatic HER2-positive breast cancer in adult patients and with an aromatase inhibitor in postmenopausal patients.[L49324] For HER2-positive early breast cancer, the EMA approved trastuzumab as monotherapy following surgery, chemotherapy (neoadjuvant or adjuvant), and radiation or following adjuvant chemotherapy with doxorubicin and cyclophosphamide in combination with paclitaxel or docetaxel. It can also be used in combination with adjuvant chemotherapy consisting of docetaxel and carboplatin or with neoadjuvant chemotherapy followed by adjuvant trastuzumab therapy for locally advanced (including inflammatory) disease or tumors > 2 cm in diameter.[L49324] Trastuzumab is also indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease by the FDA and EMA.[L14015] Trastuzumab is indicated for subcutaneous administration - in combination with either [hyaluronidase][L14132] or both hyaluronidase and [pertuzumab][L14510] - for the treatment of adults with HER2-positive breast cancers.

Trastuzumab exerts an antitumour activity and is used in the treatment of HER2-positive breast cancer. HER2 protein overexpression is observed in 20%-30% of primary breast cancers [A40277] thus HER2 presents as a useful therapeutic target for the treatment of breast cancers. Trastuzumab has been shown, in both _in vitro_ assays and in animals, to inhibit the proliferation of human tumour cells that overexpress HER2. It works as a mediator of antibody-dependent cellular cytotoxicity, where it binds as an antibody to cells over-expressing HER2, leading to preferential cell death. Trastuzumab was also shown to inhibit angiogenesis of tumor cells _in vivo_ [A121]. Higher doses and longer dosing intervals show no significant benefit over standard dose schedules [A40276]. In patients with HER2 positive solid tumours, trastuzumab did not exert any clinically significant QTc interval duration.[L14015]

Trastuzumab is a recombinant humanized IgG1 monoclonal antibody against the HER-2 receptor, a member of the epidermal growth factor receptors which is a photo-oncogene. Over-expressed in breast tumour cells, HER-2 overamplifies the signal provided by other receptors of the HER family by forming heterodimers [A121]. The HER-2 receptor is a transmembrane tyrosine kinase receptor that consists of an extracellular ligand-binding domain, a transmembrane region, and an intracellular or cytoplasmic tyrosine kinase domain. It is activated by the formation of homodimers or heterodimers with other EGFR proteins, leading to dimerization and autophosphorylation and/or transphosphorylation of specific tyrosine residues in EGFR intracellular domains [A121]. Further downstream molecular signaling cascades are activated, such as the Ras/Raf/mitogen-activated protein kinase (MAPK), the phosphoinositide 3-kinase/Akt, and the phospholipase Cγ (PLCγ)/protein kinase C (PKC) pathways that promote cell growth and survival and cell cycle progression [A121]. Due to upregulation of HER-2 in tumour cells, hyperactivation of these signaling pathways and abnormal cell proliferation is observed. Trastuzumab binds to the extracellular ligand-binding domain and blocks the cleavage of the extracellular domain of HER-2 to induce its antibody-induced receptor downmodulation [A121], and subsequently inhibits HER-2-mediated intracellular signaling cascades. Inhibition of MAPK and PI3K/Akt pathways lead to an increase in cell cycle arrest, and the suppression of cell growth and proliferation [A121]. Trastuzumab also mediates the activation of antibody-dependent cell-mediated cytotoxicity (ADCC) [A40276] by attracting the immune cells, such as natural killer (NK) cells, to tumor sites that overexpress HER-2 [A121]. While the drug alone has a minimal potential to induce complement-dependent cytotoxicity (CDC),[A201902] one study demonstrated increased therapeutic effectiveness and a synergistic effect on uterine serous carcinoma cells _in vitro_ when used in combination with [pertuzumab], which also has minor effects on CDC alone. This study showed that only the combination of both cell-bound antibodies would be sufficient to bind and activate the complement component 1q (C1q) required to initiate the complement cascade reaction.[A201896] Intrinsic trastuzumab resistance has been noted for some patients with HER-2 positive breast cancer. Mechanisms involving trastuzumab resistance include deficiency of phosphatase and tensin homologue and activation of phosphoinositide 3-kinase, and the overexpression of other surface receptors, such as insulin-like growth factor [A40276].

Peak and trough plasma concentrations at steady state (between weeks 16 and 32) were approximately 123 and 79 mcg/mL, respectively. At the highest weekly dose studied (500 mg), mean peak serum concentration was 377 mcg/mL.[L14015]

After it binds to HER2, trastuzumab is metabolized intracellularly into smaller peptides and amino acids.[A40276]

There is no experience with overdosage of trastuzumab in clinical trials - single doses >8 mg/kg have not been tested in humans.[L14015] Trastuzumab can contribute to the development of ventricular dysfunction and congestive heart failure, particularly when used in combination (or temporally adjacent) to other cardiotoxic chemotherapies such as anthracyclines.[L14015]

The terminal half-life is approximately 28 days,[A40276] but may decrease with lower doses - at the 10mg and 500mg doses, half-lives averaged approximately 1.7 and 12 days, respectively.[L6214]

null

Following metabolism, the complex elimination of trastuzumab in humans is mediated by epithelial cells in a dose-dependent (nonlinear) fashion.[A40276] The renal excretion of trastuzumab is very low.[A40276]

null

The predicted steady-state clearance of trastuzumab is 0.173 - 0.337 L/day, dependent primarily on the dosing regimen.[L14015] The clearance rate for subcutaneously administered trastuzumab, formulated with hyaluronidase for improved subcutaneous absorption, is 0.11 L/day.[L14132]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L01FD", "L01F", "L01", "L", "L01FY", "L01F", "L01", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "3443.46", "description": "Herceptin 440 mg vial", "unit": "vial" }, { "cost": "3581.2", "description": "Herceptin 440 mg Solution Vial", "unit": "vial" } ]

[ { "approved": "2005-03-22", "country": "Canada", "expires": "2012-06-15", "number": "2103059" } ]

[ "Adheroza", "Adheroza", "Herceptin", "Herceptin", "Herceptin", "Herceptin", "Herceptin", "Herceptin", "Herceptin", "Herceptin Hylecta", "Herceptin Sc", "Herwenda", "Herzuma", "Herzuma", "Herzuma", "Herzuma", "Herzuma", "Herzuma", "Kanjinti", "Kanjinti", "Kanjinti", "Kanjinti", "Kanjinti", "Kanjinti", "Kanjinti", "Ogivri", "Ogivri", "Ogivri", "Ogivri", "Ogivri", "Ogivri", "Ogivri", "Ogivri", "Ogivri", "Ogivri", "Ontruzant", "Ontruzant", "Ontruzant", "Ontruzant", "Ontruzant", "Ontruzant", "Ontruzant Solution for Infusion", "Ontruzant Solution for Infusion", "Perjeta-herceptin", "Phesgo", "Phesgo", "Phesgo", "Phesgo", "Phesgo", "Phesgo", "Trazimera", "Trazimera", "Trazimera", "Trazimera", "Trazimera", "Trazimera", "Tuznue", "Tuznue", "Z Ercepac", "Zercepac", "Zercepac" ]

[ "Herclon" ]

[ "Herceptin Hylecta", "Perjeta-herceptin", "Ogivri", "Phesgo", "Phesgo", "Phesgo", "Phesgo", "Phesgo", "Phesgo" ]

[ "P04626" ]

[]

DB00073

Rituximab

Rituximab is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. The antibody is an IgG1 kappa immunoglobulin containing murine light and heavy-chain variable region sequences and human constant region sequences [A40017], [FDA label]. It was originally approved by the U.S. FDA in 1997 as a single agent to treat patients with B-cell Non-Hodgkin's Lymphoma (NHL) [L4811], however, has now been approved for a variety of conditions [FDA label]. On November 28, 2018, the US FDA approved _Truxima_, the first biosimilar to Rituxan (Rituximab) [L4808].

liquid

Rituximab is indicated for the treatment of adult patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin’s Lymphoma (NHL) as a single agent. Also, it is indicated for the treatment of adult patients with previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy.[L26641,L42025,L42030,L42035,L42040] Additionally, rituximab is indicated for the treatment of adult patients with non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy; and previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens.[L26641,L42025,L42030,L42035,L42040] Rituximab, in combination with fludarabine and cyclophosphamide (FC), is indicated for the treatment of adult patients with previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL).[L26641,L42025,L42030,L42035,L42040] In combination with methotrexate, rituximab is indicated for the treatment of adult patients with moderately-to severely-active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.[L26641,L42025,L42030,L42035] Additionally, rituximab, in combination with glucocorticoids, is indicated for the treatment of adult and pediatric patients 2 years of age and older with Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA).[L26641,L42025,L42030,L42035] RITUXAN (rituximab injection for intravenous use) is indicated for the treatment of pediatric patients aged 6 months and older with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or mature B-cell acute leukemia (B-AL) in combination with chemotherapy; as well as the treatment of adult patients with moderate to severe pemphigus vulgaris.[L26641] These indications for RITUXAN are not included in the labels of rituximab biosimilar products (rituximab-arrx, rituximab-abbs, rituximab-pvvr).[L42025,L42030,L42035] The combination product RITUXAN HYCELA (rituximab and hyaluronidase human injection, for subcutaneous use) is not indicated for the treatment of non-malignant conditions.[L42040]

Rituximab is a chimeric murine/human monoclonal antibody that binds to the CD20 antigen. CD20 is predominantly expressed on the surface of pre-B and mature B-lymphocytes, allowing rituximab to target and promote lysis in this specific type of cells.[A40017,A248980,L26641]. In Non-Hodgkin's Lymphoma patients, rituximab treatment depleted circulating and tissue-based B-cells. In a study that included 166 patients, CD19-positive B-cells were depleted within three weeks, and in 83% of patients, cell depletion lasted up to 6-9 months. B-cell levels started to recover at approximately 6 months and returned to normal 12 months after treatment was completed. Approximately 14% of Non-Hodgkin's Lymphoma patients had IgM or IgG serum levels below the normal range [L26641]. Most rheumatoid arthritis (RA) patients treated with rituximab showed a near-complete depletion of peripheral B lymphocytes within 2 weeks after the first dose. Peripheral B-cell depletion was sustained for at least 6 months, and in approximately 4% of RA patients, peripheral B-cell depletion was sustained for more than 3 years after a single course of rituximab treatment.[L26641] Total IgG, IgA, and, more specifically, IgM levels were lower 24 weeks after the first cycle of rituximab treatment (2.8%, 0.8% and 10% below the lower limit of normal, respectively). However, the clinical consequences of this decrease in immunoglobulin levels in RA patients are not clear at this time. Treatment with rituximab in patients with RA was also associated with a decreased level of inflammation markers.[L26641] In patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) treated with rituximab, CD19 B-cells in peripheral blood were depleted to less than 10 cells/μl after the first two infusions. By month 6, approximately 84% of patients had the same level of peripheral blood CD19 B-cells, and by month 12, 81% of patients demonstrated signs of B-cell return with counts >10 cells/μL. By Month 18, the majority of patients (87%) had counts >10 cells/μL [L26641].

Rituximab is a monoclonal antibody that targets CD20, an antigen expressed on the surface of pre-B and mature B-lymphocytes [A124,A125,A126,L26641]. About 85% of non-Hodgkin’s lymphoma (NHL) cases are B-cell lymphomas, characterized by the high expression of CD19, CD20 and CD22 cell surface antigens.[A248980] CD20 is involved in cell cycle regulation, apoptosis and calcium signaling. By targeting CD20, rituximab promotes cell lysis while sparing hematopoietic and plasma cells without this surface antigen.[A40017,A248980] It has been suggested that cell lysis mechanisms triggered by rituximab include complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) [L26641]. Rituximab is part of the immunoglobulin G1 (IgG1) subclass of antibodies, and is formed by a murine variable region (Fab region) and a human constant region (Fc region). The Fab region gives rituximab its specificity for CD20, while the Fc region interacts with cell surface receptors to activate the immune system, leading to the depletion of circulating B lymphocytes [A40017]. In regards to the mechanism of action in rheumatoid arthritis (RA), B-cells are thought to play a role in the pathogenesis of RA and the associated condition of chronic synovitis.[L26641] B-cells may act at various sites in the autoimmune/inflammatory process through the production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and the production of proinflammatory cytokines [L26641]. The administration of rituximab in this condition has resulted in significant clinical and symptomatic improvements [A125,L26641]. Rituximab is also indicated for the treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), two conditions characterized by the presence of circulating antineutrophil cytoplasmic antibodies and increased B-cell activity. It has been suggested that rituximab depletes CD20+ B-cells at a higher rate in GPA and MPA patients with high levels of Fc receptor-like 5 (FCRL5).[A248985]

Rituximab follows a linear pharmacokinetic model.[A40006] In patients with non-Hodgkin’s lymphoma (NHL) administered 4 doses of 375 mg/m2 of rituximab (IV) weekly, detectable levels were observed 3-6 months after treatment completion. The pharmacokinetic profile of rituximab administered in combination with 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy was similar to the one observed when administered alone.[L26641] In patients with rheumatoid arthritis (RA) administered 2 doses of 500 mg of rituximab, the Cmax of the first and second infusions were 157 (SD ± 46) and 183 (SD ± 55) mcg/mL. In patients administered 2 doses of 1,000 mg of rituximab, the Cmax of the first and second infusions were 318 (SD ± 86) and 381 (SD ± 98) mcg/mL.[L26641] In pediatric patients (6-17 years old) with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) given four doses of 375 mg/m2 of rituximab intravenously once a week, the AUC0-180 was 9787 µg/mL⋅day (range from 4838 to 20446 µg/mL⋅day). In adult patients given the same dose, the AUC0-180 of rituximab was 10302 µg/mL⋅day (range from 3653 to 21874 µg/mL⋅day).[L26641] The bioavailability of rituximab administered intravenously is expected to be close to 100%. Compared to rituximab administered intravenously, the bioavailability of RITUXAN HYCELA, a combination product of rituximab and hyaluronidase (human recombinant), is 64.6% in patients with follicular lymphoma and 63.4% in patients with chronic lymphocytic leukemia (CLL).[L42040]

As a monoclonal antibody, rituximab is expected to be metabolized by proteases throughout the body.

Toxicity information regarding rituximab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as fatal infusion-related reactions and severe mucocutaneous reactions. Symptomatic and supportive measures are recommended. No long-term animal studies have been performed to establish the carcinogenic or mutagenic potential of rituximab or to determine potential effects on fertility in males or females [L26641]. The maximum tolerated dose of rituximab in mice administered intraperitoneally is higher than 100 mg/kg.[L42045]

In patients with non-Hodgkin's lymphoma (NHL) treated with rituximab once a week or once every three weeks (n=298), the median terminal elimination half-life was 22 days (range of 6.1-52 days).[L26641] In patients with chronic lymphocytic leukemia (CLL) treated with rituximab (n=21), the estimated median terminal half-life was 32 days (range of 14-62 days).[L26641] Based on a pharmacokinetic analysis that included 2005 patients with rheumatoid arthritis (RA), the mean terminal elimination half-life of rituximab is 18.0 days.[L26641] In pediatric patients (6-17 years old) with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) given four doses of 375 mg/m2 of rituximab intravenously once a week, the terminal half-life was 22 days (range from 11 to 42 days). In adult patients given the same dose, the terminal half-life was 25 days (range from 11 to 52 days).[L26641] In patients with pemphigus vulgaris given an intravenous infusion of 1000 mg of rituximab, the terminal half-life was 21.1 days (range from 9.3 to 36.2 days) in the first infusion cycle (days 1 and 15), and 26.2 days (range from 16.4 to 42.8 days) in the second infusion cycle (days 168 and 182).[L26641]

Not available.

Monoclonal antibodies (mAb) such as rituximab trigger the formation of antidrug antibodies (ADAs) that form ADA-mAb immune complexes. The endogenous elimination of these immune complexes is mediated by the reticuloendothelial system, most likely via fragment crystallizable-gamma (Fcγ)-mediated endocytosis[A40006].

Based on a pharmacokinetic analysis that included 2005 patients with rheumatoid arthritis (RA), the volume of distribution of rituximab is 3.1 L.[L26641] In pediatric patients (6-17 years old) with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) given four doses of 375 mg/m2 of rituximab intravenously once a week, the volume of distribution was 2.28 L (range from 1.43 to 3.17 L). In adult patients given the same dose, the volume of distribution was 3.12 L (range from 2.42 to 3.91 L).[L26641] In patients with pemphigus vulgaris given an intravenous infusion of 1000 mg of rituximab on days 1, 15, 168, and 182, the volume of distribution was 3.49 L (range from 2.48 to 5.22 L).[L26641]

In patients with non-Hodgkin’s lymphoma (NHL), those with higher CD19-positive cell counts or larger measurable tumor lesions at pretreatment had higher rituximab clearance [L26641]. Based on a pharmacokinetic analysis that included 2005 patients with rheumatoid arthritis (RA), the clearance of rituximab is 0.335 L/day.[L26641] In pediatric patients (6-17 years old) with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) given four doses of 375 mg/m2 of rituximab intravenously once a week, clearance was 0.222 L/day (range from 0.0996 to 0.381 L/day). In adult patients given the same dose, clearance was 0.279 L/day (range from 0.113 to 0.653 L/day).[L26641] In patients with pemphigus vulgaris given an intravenous infusion of 1000 mg of rituximab, clearance was 0.30 L/day (range from 0.16 to 1.51 L/day) in the first infusion cycle (days 1 and 15), and 0.24 L/day (range from 0.13 to 0.45 L/day) in the second infusion cycle (days 168 and 182).[L26641]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "L01FA", "L01F", "L01", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "68.09", "description": "Rituxan 10 mg/ml vial", "unit": "ml" }, { "cost": "708.17", "description": "Rituxan 10 mg/ml Concentrate 10ml Vial", "unit": "vial" } ]

[ { "approved": "2008-07-15", "country": "Canada", "expires": "2013-11-12", "number": "2149329" }, { "approved": "1995-08-29", "country": "Canada", "expires": "2012-08-29", "number": "1336826" }, { "approved": "1998-04-07", "country": "United States", "expires": "2015-04-07", "number": "5736137" } ]

[ "Blitzima", "Blitzima", "Mabthera", "Mabthera", "Mabthera", "Mabthera", "Riabni", "Riabni", "Riabni", "Ritemvia", "Ritemvia", "Rituxan", "Rituxan", "Rituxan", "Rituxan Hycela", "Rituxan Hycela", "Rituxan Sc", "Rituxan Sc", "Rituzena", "Rituzena", "Rixathon", "Rixathon", "Rixathon", "Rixathon", "Riximyo", "Riximyo", "Riximyo", "Riximyo", "Riximyo", "Ruxience", "Ruxience", "Ruxience", "Ruxience", "Ruxience", "Truxima", "Truxima", "Truxima", "Truxima", "Truxima", "Truxima" ]

[ "MabThera", "Riabni" ]

[ "Rituxan Hycela", "Rituxan Hycela" ]

[ "P11836" ]

[]

DB00074

Basiliximab

A recombinant chimeric (murine/human) monoclonal antibody (IgG1k) that functions as an immunosuppressive agent, specifically binding to and blocking the interleukin-2 receptor a-chain (IL-2R alpha, also known as CD25 antigen) on the surface of activated T-lymphocytes. It is a 144 kDa glycoprotein obtained from fermentation of an established mouse myeloma cell line genetically engineered to express plasmids containing the human heavy and light chain constant region genes and mouse heavy and light chain variable region genes encoding the RFT5 antibody that binds selectively to the IL-2R alpha.

liquid

For prophylactic treatment of kidney transplant rejection

Basiliximab functions as an IL-2 receptor antagonist. Specifically it inhibits IL-2-mediated activation of lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection.

Basiliximab binds with high-affinity to the alpha-subunit (CD25) of the high-affinity IL-2 receptor. This inhibits IL-2 binding, which inhibits T-cell activation and prevents the body from mounting an immune response against the foreign kidney.

null

Most likely removed by opsonization via the reticuloendothelial system when bound to lymphocytes, or by human antimurine antibody production

null

7.2 +/- 3.2 days (adults)

null

* 7.8 ± 5.1 L [Pediatric] * 4.8 ± 2.1 L [Adult]

* 41 +/- 19 mL/h [Adult patients undergoing first kidney transplantation] * 17 +/- 6 mL/h [pediatric patients undergoing renal transplantation] * 31 +/- 19 mL/h [adolescent patients undergoing renal transplantation]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L04AC", "L04A", "L04", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "1883.11", "description": "Simulect 10 mg vial", "unit": "vial" }, { "cost": "2471.6", "description": "Simulect 20 mg vial", "unit": "vial" } ]

[ { "approved": "1999-03-09", "country": "Canada", "expires": "2011-03-11", "number": "2038279" } ]

[ "Simulect", "Simulect", "Simulect", "Simulect", "Simulect", "Simulect", "Simulect" ]

[]

[ "P01589", "P14784" ]

[]

DB00075

Muromonab

Murine monoclonal antibody specific to CD3 T-cell lymphocyte antigens. More specifically it is a purified murine (mouse) monoclonal antibody, directed against the CD3 (T3) receptor on the surface of human T-cells (T-lymphocytes) cultured using the murine ascites method. Muromonab is 93% monomeric immune globulin G type 2a (IgG2a).

liquid

For treatment of organ transplant recipients, prevention of organ rejection

Used in organ transplant prophylaxis, Muromonab or OKT-3 binds specifically to the CD-3 complex, which is involved in antigen recognition and cell stimulation, on the surface of T lymphocytes. Immediately after administration CD-3-positive T lymphocytes are abruptly removed from circulation. It has been effective in reversing corticosteroid-resistant acute rejection in renal, liver, and cardiac transplant recipients.

Muromonab binds to the T-cell surface glycoprotein CD3 epsilon chain. It appears to kill CD-3 positive cells by inducing Fc mediated apoptosis, antibody mediated cytotoxicity and complement-dependent cytotoxicity.

null

Most likely removed by opsonization via the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production

null

0.8 hours (mammalian reticulocytes, in vitro)

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L04AG", "L04A", "L04", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "261.75", "description": "Orthoclone okt-3 5 mg/5 ml", "unit": "ml" } ]

[]

[ "Okt3", "Orthoclone Okt 3 Sterile Solution IV 1mg/ml" ]

[ "Orthoclone OKT3" ]

[]

[ "P04234", "P07766", "P09693", "P20963", "O75015" ]

[]

DB00076

Digoxin Immune Fab (Ovine)

Digoxin Immune Fab is a sheep antibody (26-10) FAB fragment from sheep immunized with the digoxin derivative Digoxindicarboxymethylamine. It is used as an antidote for overdose of digoxin.

liquid

For treatment of digitoxin overdose or digitalis glycoside toxicity.

DigiFab binds molecules of digoxin, making them unavailable for binding at their site of action on cells in the body. The Fab fragment-digoxin complex accumulates in the blood, from which it is excreted by the kidney. The net effect is to shift the equilibrium away from binding of digoxin to its receptors in the body, thereby reversing its effects.

Binds excess digoxin or digitoxin molecules circulating in the blood.

null

15-20 hrs

null

Cumulative urinary excretion of digoxin was comparable for both products and exceeded 40% of the administered dose by 24 hours.

* 0.3 L/kg [DigiFab] * 0.4 L/kg [Digibind]

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "V03AB", "V03A", "V03", "V" ]

[ "Humans and other mammals" ]

[ { "cost": "615.6", "description": "Digifab 40 mg vial", "unit": "vial" }, { "cost": "727.91", "description": "Digibind 38 mg vial", "unit": "vial" } ]

[]

Digitalis antitoxin | Digoxin Immune Fab, Ovine | Digoxin-specific Antibody Fragments | Ovine digoxin immune fab

[ "Digibind", "Digibind", "DigiFab", "DigiFab", "DigiFab" ]

[]

DB00078

Ibritumomab tiuxetan

Indium or yttrium conjugated murine IgG1 kappa monoclonal antibody directed against the CD20 antigen, which is found on the surface of normal and malignant B lymphocytes. Ibritumomab is produced in Chinese hamster ovary cells and is composed of two murine gamma 1 heavy chains of 445 amino acids each and two kappa light chains of 213 amino acids each.

liquid

For treatment of non-Hodgkin's lymphoma

Ibritumomab is a murine monoclonal antibody against CD20 that has been radiolabeled with yttrium-90.

The Fab segment of the antibody targets the CD20 epitope on B-cells, allowing the radioactive yttrium to destroy the cell via production of beta particles.

null

Most likely removed by opsonization via the reticuloendothelial system when bound to B cells, or by human antimurine antibody production

null

0.8 hours (mammalian reticulocytes, in vitro)

null

Binding observed on lymphoid cells of the bone marrow, lymph node, thymus, red and white pulp of the spleen, lymphoid follicles of the tonsil, and lymphoid nodules of other organs (e.g., large and small intestines)

Approximately 7.2% of injected dose of yttrium Y 90 ibritumomab tiuxetan is excreted in urine within 7 days.

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "V10XX", "V10X", "V10", "V" ]

[ "Humans and other mammals" ]

[ { "cost": "4200.0", "description": "Zevalin in-111 kit", "unit": "kit" }, { "cost": "37800.0", "description": "Zevalin y-90 kit", "unit": "kit" } ]

[ { "approved": "2008-07-15", "country": "Canada", "expires": "2013-11-12", "number": "2149329" } ]

[ "Zevalin", "Zevalin", "Zevalin", "Zevalin" ]

[]

[ "P11836" ]

[]

DB00080

Daptomycin

Daptomycin is a cyclic lipopeptide antibacterial agent with a broad spectrum of activity against Gram-positive bacteria, including methicillin-susceptible and -resistant _Staphylococcus aureus_ (MSSA/MRSA) and vancomycin-resistant Enterococci (VRE).[A231379, A231384, L32534] Chemically, daptomycin comprises 13 amino acids, including several non-standard and D-amino acids, with the C-terminal 10 amino acids forming an ester-linked ring and the N-terminal tryptophan covalently bonded to decanoic acid.[A231374, L32534] Daptomycin was first discovered in the early 1980s by researchers at Eli Lilly in soil samples from Mount Ararat in Turkey.[A231384] Early work on developing daptomycin was abandoned due to observed myopathy but was resumed in 1997 when Cubist Pharmaceuticals Inc. licensed daptomycin; it was found that a once-daily dosing scheme reduced side effects while retaining efficacy.[A231379] Daptomycin was approved by the FDA on September 12, 2003, and is marketed under the name CUBICIN® by Cubist Pharmaceuticals LLC (Merck & Co.).[L32534]

solid

Daptomycin is indicated for the treatment of complicated skin and skin structure infections (cSSSI) in patients one year of age and older. It is also indicated for the treatment of _Staphylococcus aureus_ bloodstream infections (bacteremia) in patients one year of age and older, including in adult patients with right-sided infective endocarditis.[L32534] Daptomycin is not indicated for the treatment of pneumonia or left-sided infective endocarditis due to _S. aureus_. Use is not recommended in pediatric patients younger than one year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central).[L32534] As with all antibacterial drugs, it is strongly suggested to perform sufficient testing before treatment initiation in order to confirm an infection caused by susceptible bacteria. Failure to do so may result in suboptimal treatment, treatment failure, and the development of drug-resistant bacteria.[L32534]

Daptomycin is a cyclic lipopeptide antibacterial agent produced as a fermentation product by the soil microbe _Streptomyces roseosporus_. The daptomycin core consists of 13 amino acids, including three D-amino acids, ornithine, 3-methyl-glutamic acid, and kynurenine, with the C-terminal 10 amino acids forming an ester-linked ring and the N-terminal tryptophan covalently bonded to decanoic acid.[A231374, L32534] Daptomycin is active against aerobic Gram-positive bacteria, including clinically relevant strains such as methicillin-susceptible and -resistant _Staphylococcus aureus_ (MSSA/MRSA), vancomycin-resistant _S. aureus_, vancomycin-resistant Enterococci (VRE), _Staphylococcus_ spp., _Streptococcus_ spp., _Clostridiodes difficile_, _Clostridium perfringens_, _Finegoldia magna_, and _Propionibacterium acnes_, among others.[A231379, A231384, L32534] Although daptomycin is active against _Streptococcus pneumoniae_ _in vitro_, it is inhibited by lung surfactant, and hence is not effective for the treatment of pneumonia or other similar lung infections.[A231379, A231389, L32534] Daptomycin exhibits rapid concentration-dependent bactericidal activity _in vitro_, which correlates best with the ratio of the area under the concentration-time curve to the minimum inhibitory concentration (AUC/MIC) in animal models of infection.[L32534] Like other antibacterial agents, daptomycin carries a risk of severe hypersensitivity reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). There have been reports of myopathy, rhabdomyolysis, and increased creatine phosphokinase (CPK) levels in patients taking daptomycin, which increased when daptomycin was given more than once per day. Patients should be monitored for CPK levels and, in those with renal impairment, renal function, at least once per week and should consider temporarily suspending the use of HMG-CoA reductase inhibitors. Daptomycin should not be administered more than once per day. Severe adverse reactions such as tubulointerstitial nephritis and peripheral neuropathy have been reported, which may require treatment discontinuation. Based on animal studies, patients less than one year of age may experience serious muscular, neuromuscular, and nervous system effects; daptomycin is not recommended for use in patients under one year of age. Patients undergoing daptomycin treatment may experience eosinophilic pneumonia and _Clostridioides difficile_-associated diarrhea, both of which may require the cessation of antibacterial treatment and initiation of symptomatic/supportive measures. Persisting or relapsing _S. aureus_ bacteremia and endocarditis should be investigated for sequestered foci of infection and the possibility of daptomycin resistance; the dose or treatment regimen may require adjusting. Patients with moderate to severe renal impairment (creatine clearance < 50 mL/min) experienced reduced clinical benefit from daptomycin treatment based on limited data. Clinically relevant daptomycin plasma concentrations have significantly affected prothrombin time and International Normalized Ratio (INR) measurements. As with all antibiotics, daptomycin use may promote the overgrowth of non-susceptible organisms and the development of resistant organisms; daptomycin use should be limited to cases where it is proven or strongly suspected that an infection is caused by susceptible bacteria.[L32534]

The mechanism of action of daptomycin remains poorly understood. Studies have suggested a direct inhibition of cell membrane/cell wall constituent biosynthesis, including peptidoglycan, uridine diphosphate-N-acid, acetyl-L-alanine, and lipoteichoic acid (LTA). However, no convincing evidence has been presented for any of these models, and an effect on LTA biosynthesis has been ruled out by other studies in _S. aureus_ and _E. faecalis_.[A231384, A231394, A14171] It is well understood that free daptomycin (apo-daptomycin) is a trianion at physiological pH, which binds Ca2+ in a 1:1 stoichiometric ratio to become a monoanion, which is thought to rely primarily on the Asp(7), Asp(9), and L-3MeGlu12 residues that form a DXDG motif.[A231374, A231379, A231384] Calcium-binding facilitates daptomycin's insertion into bacterial membranes preferentially due to their high content of the acidic phospholipids phosphatidylglycerol (PG) and cardiolipin (CL), wherein it is proposed that daptomycin can bind two calcium equivalents and form oligomers.[A231379] PG is recognized as the main membrane requirement for daptomycin activity; daptomycin preferentially localizes in PG-rich membrane domains, and mutations affecting PG prevalence are linked to daptomycin resistance.[A231379] Calcium-dependent membrane binding is the generally accepted mechanism of action for daptomycin, but the precise downstream effects are unclear, and numerous models have been proposed. One mechanism proposes that the daptomycin membrane binding alters membrane fluidity, causing dissociation of cell wall biosynthetic enzymes such as the lipid II synthase MurG and the phospholipid synthase PlsX.[A231384] This is consistent with the observed effects of daptomycin on cell shape in various bacteria at concentrations at or above the minimum inhibitory concentration (MIC).[A14171] Aberrant cell morphology is also consistent with the observed localization of daptomycin at the division septa and a hypothesized role in inhibiting cell division.[A231379] A recent study suggested the formation of tripartite complexes containing calcium-bound daptomycin, PG, and various undecaprenyl-coupled cell envelope precursors, which subsequently include lipid II. This complex is proposed to inhibit cell division, lead to the dispersion of cell wall biosynthetic machinery, and eventually cause lysis of the membrane bilayer at the septum causing cell death.[A231384, A231409] Another popular model is based on early observations that daptomycin, in a calcium-dependent manner, caused potassium ion leakage and loss of membrane potential in treated bacterial cells.[A231394, A231419, A231424] Although this lead some to suggest that daptomycin could bind PG to form oligomeric pores in the bacterial membrane,[A231384] no cell lysis was observed in _S. aureus_ or _E. faecalis_,[A231379] and the daptomycin-induced ion conduction is inconsistent with pore formation.[A231429] Rather, it has been proposed that daptomycin forms calcium-dependent dimeric complexes in fixed ratios of Dap2Ca3PG2, which can act as transient ionophores.[A231429] The observed loss of membrane potential is suggested to result in a non-specific loss of gradient-dependent nutrient transport, ATP production, and biosynthesis, leading to cell death.[A231379, A231424] Notably, these models are not strictly mutually exclusive and are supported to varying extents by observed resistance mutations. The strict requirement for PG for daptomycin bactericidal action is supported by mutations in _mprF_, _cls2_, _pgsA_, and the _dlt_ operon in _S. aureus_, _cls_ in various enterococci, and _pgsA_, PG synthase, and the _dlt_ operon in _E. faecium_, all of which alter the bacterial membrane composition and specifically the PG content of bacterial membranes. Other noted mutations in various regulatory systems that control membrane homeostasis also support the cell membrane as the site of daptomycin action. Curiously, in _E. faecalis_, the most commonly observed form of daptomycin resistance is characterized by abnormal division septa, which supports the cell division-based mechanism of daptomycin action.[A231379, A231384]

Daptomycin administered as a 30 minute IV infusion to healthy volunteers in doses of 4, 6, 8, 10, and 12 mg/kg once daily resulted in a Cmax between 57.8 ± 3.0 and 183.7 ± 25.0 μg/mL and an AUC0-24 of between 494 ± 75 and 1277 ± 253 μg\*h/mL.[A231449, L32534] Daptomycin pharmacokinetics are generally linear, with some variation observed above 6 mg/kg, and the Cmax and AUC values are approximately 20% higher at steady-state, suggesting some accumulation.[A231449] Steady-state trough concentrations between 5.9 ± 1.6 and 13.7 ± 5.2 μg/mL are reached following the third once-daily dose.[L32534] The data for a single daptomycin dose of 6 mg/kg administered IV over 30 minutes was used to estimate steady-state Cmax values for both 4 and 6 mg/kg doses administered over two minutes, which were estimated at 77.7 ± 8.1 and 116.6 ± 12.2 μg/mL, respectively. Administration of IV daptomycin (4 or 6 mg/kg) over two minutes did not allow for measurement of the Cmax but resulted in steady-state AUC values of 475 ± 71 and 701 ± 82 μg\*h/mL.[L32534] Patients with severe renal impairment and those on dialysis had mean steady-state AUC values approximately 2-3 times higher than those with normal renal function. No clinically significant differences in daptomycin pharmacokinetics were observed in patients with mild to moderate hepatic impairment. The mean AUC0-∞ obtained in healthy elderly individuals (75 years of age and older) was approximately 58% higher than in healthy young adult controls, with no difference in Cmax. The AUC0-∞ is also increased in obese patients by approximately 30%. No significant differences in body weight- and age-adjusted Cmax or AUC was observed in pediatric patients.[L32534]

Radiolabeled daptomycin administered to five healthy adults revealed the presence of inactive metabolites in the urine. A separate study using 6 mg/kg daptomycin in healthy adults revealed small amounts of three oxidative and one unidentified metabolite(s) in urine but not in plasma.[L32534] The site of metabolism is unclear, as studies using human hepatocytes suggest that daptomycin effectively does not interact at all with the various CYP450 enzymes present in the liver.[A231474, L32534]

Toxicity information regarding daptomycin is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as myopathy, rhabdomyolysis, muscular/neurological system symptoms, eosinophilic pneumonia, tubulointerstitial nephritis, vomiting/diarrhea, abdominal pain, headache, dizziness, pyrexia, sweating, and pruritus. Symptomatic and supportive measures are recommended, including maintenance of glomerular filtration. Due to its high serum protein binding, daptomycin is not easily removed by hemodialysis (~15% of a dose over four hours) or peritoneal dialysis (~11% of a dose over 48 hours). High-flux membranes in hemodialysis may improve the quantity of daptomycin removed using this approach.[L32534]

Daptomycin has a relatively long half-life, with ranges of 7.5-9 hours depending on dosing schemes and dose strength.[A231449, L32534] The half-life lengthens in patients with increasing renal impairment, being 27.83 ± 14.85 hours in patients with creatinine clearance <30 mL/min, 30.51 ± 6.51 hours in hemodialysis patients, and 27.56 ± 4.53 hours in continuous ambulatory peritoneal dialysis (CAPD) patients. Daptomycin half-life also tends to decrease with decreasing age.[L32534]

Daptomycin reversibly binds plasma proteins between 90-94% and independently of concentration.[A231449, L32534, A231574, A231579] Although daptomycin is mainly bound to serum albumin (HSA; 85-96%), it also binds appreciably to α-1-acid-glycoprotein (AGP; 25-51%).[A231574, A231579, A231584] Surface plasmon resonance (SPR) experiments revealed that daptomycin also binds a number of other plasma proteins including α-1-antitrypsin, low-density lipoprotein (LDL), hemoglobin, sex hormone-binding globulin (SHBG), hemopexin, fibrinogen, α2-macroglobulin, β2-microglobulin, high-density lipoprotein (HDL), fibronectin, haptoglobulin, transferrin, and IgG.[A231579] Of these, it was determined that the main determinants of plasma binding were HSA, AGP, α-1-antitrypsin, LDL, SHBG, and hemopexin.[A231579] Consistent with observations regarding calculated distribution volumes, daptomycin protein binding tends to decrease with decreasing renal function, being approximately 88% in patients with creatinine clearance <30 mL/min, approximately 86% in those on hemodialysis, and approximately 84% in those on continuous ambulatory peritoneal dialysis (CAPD).[L32534]

Daptomycin is excreted primarily by the kidneys, approximately 78% of an administered dose recovered in urine and only 5.7% recovered in feces.[A231449, L32534] Approximately 52% of the dose, recovered in urine, retains microbiological activity.[L32534]

Daptomycin has a very small volume of distribution, averaging ~0.1 L/kg in healthy adult subjects independent of dose.[A231449, L32534] The volume of distribution tends to increase with decreasing renal function, being estimated at ~0.2 L/kg in patients with severe renal impairment.[L32534]

Daptomycin administered as a 30 minute IV infusion to healthy volunteers in doses of 4, 6, 8, 10, and 12 mg/kg once daily resulted in total plasma clearance values between 7.2 ± 1.1 and 9.6 ± 1.3 mL/h/kg, with no clear dose association.[A231449, L32534] As daptomycin is primarily renally excreted, patients with mild, moderate, and severe renal impairment had reduced total plasma clearance 9, 22, and 46 percent lower than healthy controls, respectively. Daptomycin clearance was also lower in obese (15-23%) and geriatric (aged 75 and older, by 35%) patients, whereas it tended to be higher in pediatric patients, even when normalized for body weight.[L32534]

null

[ "approved", "investigational" ]

[ "J01XX", "J01X", "J01", "J" ]

[ "Gram-positive Bacteria" ]

[ { "cost": "272.7", "description": "Cubicin 500 mg vial", "unit": "vial" } ]

[ { "approved": "2006-07-04", "country": "Canada", "expires": "2019-09-24", "number": "2344318" }, { "approved": "2002-10-22", "country": "United States", "expires": "2019-09-24", "number": "6468967" }, { "approved": "2005-02-08", "country": "United States", "expires": "2019-09-24", "number": "6852689" }, { "approved": "2011-08-23", "country": "United States", "expires": "2028-09-04", "number": "8003673" }, { "approved": "2006-04-18", "country": "United States", "expires": "2016-06-15", "number": "RE39071" }, { "approved": "2011-11-15", "country": "United States", "expires": "2020-11-28", "number": "8058238" }, { "approved": "2012-03-06", "country": "United States", "expires": "2020-11-28", "number": "8129342" }, { "approved": "2015-09-22", "country": "United States", "expires": "2030-11-23", "number": "9138456" }, { "approved": "2019-07-23", "country": "United States", "expires": "2033-09-11", "number": "10357535" }, { "approved": "2017-05-23", "country": "United States", "expires": "2033-09-11", "number": "9655946" }, { "approved": "2021-11-16", "country": "United States", "expires": "2041-03-11", "number": "11173189" }, { "approved": "2018-08-28", "country": "United States", "expires": "2038-08-28", "number": "11759497" }, { "approved": "2018-08-28", "country": "United States", "expires": "2038-08-28", "number": "12053502" } ]

[ "Cubicin", "Cubicin", "Cubicin", "Cubicin", "Cubicin", "Cubicin", "Cubicin", "Cubicin RF", "Cubicin RF", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin", "Daptomycin for Injection", "Daptomycin for Injection", "Daptomycin for Injection", "Daptomycin for Injection", "Daptomycin for Injection", "Daptomycin for Injection", "Daptomycin for Injection", "Daptomycin for Injection", "Daptomycin for Injection RF", "Daptomycin for Injection RF", "Daptomycin for Injection RF", "Daptomycin Hospira", "Daptomycin Hospira", "Daptomycin Hospira", "Daptomycin Hospira", "Daptomycin in Sodium Chloride", "Daptomycin in Sodium Chloride", "Daptomycin in Sodium Chloride", "Daptomycin in Sodium Chloride", "Dapzura RT", "Dapzura RT" ]

[ "Cidecin", "Cubicin" ]

[]

[ "P02768", "P02763", "P01009", "P01130", "P04278", "P02790" ]

[ "P08183" ]

DB00081

Tositumomab

Murine IgG2a lambda monoclonal antibody against CD20 antigen (2 heavy chains of 451 residues, 2 lambda chains of 220 residues). It is produced in an antibiotic-free culture of mammalian cells. It can be covalently linked to Iodine 131 (a radioactive isotope of iodine).

liquid

For treatment of non-Hodgkin's lymphoma (CD20 positive, follicular)

Tositumomab binds to the CD20 antigen, which is predominantly expressed on mature B cells and on >90% of B-cell non-Hodgkin's lympohomas. The antibody leads to selective killing of B-cells.

Binds to the CD20 antigen which is found on mature B lymphocytes. The antibody binding appears to induce apoptosis, complement-dependent cytotoxicity and cell death through ionizing radiation.

null

Most likely removed by opsonization via the reticuloendothelial system when bound to B lymphocytes, or by human antimurine antibody production

null

0.8 hours (mammalian reticulocytes, in vitro)

null

Elimination of Iodine-131 occurs by decay and excretion in the urine.

null

* 68.2 mg/hr [patients with NHL]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "V10XA", "V10X", "V10", "V" ]

[ "Humans and other mammals" ]

[ { "cost": "100.43", "description": "Bexxar 14 mg/ml dosimetric", "unit": "ml" }, { "cost": "180.77", "description": "Bexxar 131 iodine dosimetric", "unit": "ml" } ]

[]

[ "Bexxar", "Bexxar", "Bexxar Dosimetric", "Bexxar Therapeutic", "Bexxar Therapy" ]

[]

[ "Bexxar", "Bexxar" ]

[ "P11836", "P31994" ]

[]

DB00082

Pegvisomant

Pegvisomant is a highly selective growth hormone (GH) receptor antagonist. It is used to treat acromegaly. Unlike dopamine or somatostatin analogs (which inhibit growth hormone secretion), this drug actually blocks the hepatic (GH-mediated) production of insulin like growth factor (IGF-1), which is the main mediator of growth hormone activity.

liquid

Pegvisomant is a growth hormone receptor antagonist used for the treatment of acromegaly.

Somavert is used for the treatment of acromegaly, which arises from excessive IGF-1 levels. Somavert selectively binds to growth hormone (GH) receptors on cell surfaces, where it blocks the binding of endogenous GH, and thus interferes with GH signal transduction. Inhibition of GH action results in decreased serum concentrations of insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3). This reduces the symptoms of acromegaly.

Somavert selectively binds to growth hormone (GH) receptors on cell surfaces, where it blocks the binding of endogenous GH. This leads to the normalization of serum IGF-1 levels.

null

~6 days

null

* 7 L

* 36 - 28 mL/h [SC doses ranging from 10 to 20 mg/day]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "H01AX", "H01A", "H01", "H" ]

[ "Humans and other mammals" ]

[ { "cost": "104.18", "description": "Somavert 10 mg vial", "unit": "vial" }, { "cost": "156.29", "description": "Somavert 15 mg vial", "unit": "vial" }, { "cost": "208.38", "description": "Somavert 20 mg vial", "unit": "vial" } ]

[ { "approved": "1994-09-27", "country": "United States", "expires": "2011-09-27", "number": "5350836" }, { "approved": "2009-05-26", "country": "Canada", "expires": "2016-09-20", "number": "2230492" }, { "approved": "2003-04-01", "country": "Canada", "expires": "2012-05-01", "number": "2102129" }, { "approved": "2000-05-02", "country": "United States", "expires": "2015-09-21", "number": "6057292" }, { "approved": "1998-12-15", "country": "United States", "expires": "2017-03-25", "number": "5849535" } ]

[ "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert", "Somavert" ]

[]

[ "P10912" ]

[ "Q02318", "P15104", "P08684", "P06276", "Q02928" ]

[]

DB00083

Botulinum toxin type A

In 2002, botulinum toxin A, also known as onabotulinumtoxinA or Botox, was the first type A botulism toxin to be introduced into the market for cosmetic use.[A231824] With a wide variety of applications and favourable safety profile, Botulinum toxin A injection is a minimally invasive and promising treatment for cosmetic imperfections, muscle spasms, and other conditions.[A231819,L32569] A popular use for Botox is the treatment of facial wrinkles and lines, however, there are many uses for the botulinum toxin A in the treatment of dystonia, incontinence, migraine, blepharospasm, and hyperhidrosis.[L32494,L32559]

solid

Botulinum toxin A is indicated for a variety of conditions, depending on the preparations. Cosmetically, it is used for the treatment of facial fine lines and wrinkles, specifically for upper facial rhytides, including forehead, lateral canthus, and glabellar lines.[L32559] In addition to the above indications, botulinum toxin A is used for the following conditions: treatment of adults with symptomatic overactive bladder with or without incontinence, treatment of incontinence in adult patients who are not candidates for anticholinergic therapy, treatment of Neurogenic Detrusor Overactivity (NDO) in patients over 5 years who cannot undergo anticholinergic therapy. Botulinum toxin A is indicated for the prevention of chronic migraines, for the treatment of muscle spasms, cervical dystonia, axillary hyperhidrosis, strabismus,[L32494] and disorders of the 7th cranial nerve.[L32569] Off-label, botulinum toxin A is used for a variety of conditions such as temporomandibular joint (TMJ) disorders and myofascial pain[A231874], neurogenic thoracic outlet syndrome, epicondylitis, post-stroke pain, post-herpetic neuralgia, diabetic neuropathy, trigeminal neuralgia, neuropathic pain, spinal cord injury, and bladder pain.[A231879]

Botulinum toxin A inhibits the release of acetylcholine, relieving muscle contraction and spasm associated with many conditions, such as incontinence and dystonia. Cosmetically, botulinum toxin A paralyses muscles in the face to temporarily treat wrinkles.[A231844,L32559] The maximum effects of muscle paralysis occur four to seven days after a dose.[A231304] When injected at therapeutic doses, botulinum toxin A causes partial chemical denervation of muscle tissue, causing local reduction of muscle activity. Muscle atrophy may result, axonal sprouting may begin, and extrajunctional acetylcholine receptors can be formed. Reinnervation of the muscle may occur, reversing muscle denervation caused by botulinum toxin A.[L32494]

Botulinum toxin is a 150-kDa molecular weight protein consisting of a light chain (50 kDa) and heavy chain (100 kDa) linked by a single disulfide bond. The crystal structure reveals 3 lobes - the light chain, the amino-terminal portion of the heavy chain, and the carboxyl-terminal portion of the heavy chain.[A231854] Botulinum toxin type A blocks neuromuscular transmission on motor or sympathetic nerve terminals, inhibiting the release of acetylcholine.[L32494] Botulinum toxins have actions on various regions: the neuromuscular junction, autonomic ganglia, and both postganglionic sympathetic and parasympathetic nerve endings. The heavy chain of the toxin binds selectively at the presynaptic surface of cholinergic neurons in an irreversible fashion. After binding, the toxin-receptor complex is transported into the cell by endocytosis. The disulfide bond between the two chains is cleaved and the botulism toxin enters the cytoplasm. The light chain specifically interacts with SNAP-25 in the nerve terminals to block binding of acetylcholine vesicles with the cell membrane. SNAP-25 is required for successful binding and release of acetylcholine from vesicles in nerve endings.[A231304]

The chemical complexity of botulinum toxin type A combined with its extreme potency limits the opportunity to study its pharmacokinetic profile in humans.[L32494] For this reason, human pharmacokinetic studies have not been performed. Animal studies using radio labeled botulinum toxin suggest it is absorbed systemically after subcutaneous and intranasal administration. Clinical relevance is unknown.[A231854]

Metabolism information for botulinum A toxin is not readily available in the literature.[A231854,L32494]

The intraperitoneal LD50 of botulinum toxin A in mice is 160 ng/kg.[L32654] An overdose of botulinum toxin A is expected to produce neuromuscular weakness, manifested by a variety of symptoms that may not appear immediately after injection. Dysphagia, dysphonia, weakness, dyspnea or respiratory distress may indicate distant spread of botulinum toxin A effects.[A231884] If an overdose is suspected or confirmed, patients should be monitored for several weeks closely for local and distant neurologic effects. Hospitalization or further medical evaluation and appropriate intervention should be provided immediately.[L32494]

There is no readily available data about the pharmacokinetics of botulinum toxin in humans.[L32494] The elimination half-life for non-metabolized botulinum toxin in blood and serum ranged from 230 to 260 min in a pharmacokinetic study of rats and mice.[A231854]

A pharmacokinetic study in mice and rats revealed significant binding to albumin after subcutaneous injection or intranasal administration.[A231854]

Elimination information for botulinum A toxin is not readily available in the literature.[A231854,L32494]

There are extremely limited data about the pharmacokinetics of botulinum toxin in humans.[L32494] An animal study demonstrated that botulinum toxin accumulates in the liver and spleen in rats and mice when injected subcutaneously or administered intranasally.[A231854]

Clearance information for botulinum A toxin is not readily available in the literature.[A231854,L32494]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "M03AX", "M03A", "M03", "M" ]

[ "Humans and other mammals" ]

[ { "cost": "3.74", "description": "Botox (100 - 200 unit/Vial)", "unit": "vial" }, { "cost": "346.8", "description": "Botox cosmetic 50 unit vial", "unit": "vial" }, { "cost": "630.0", "description": "Botox 100 unit vial", "unit": "vial" }, { "cost": "630.0", "description": "Botox cosmetic 100 unit vial", "unit": "vial" }, { "cost": "655.2", "description": "Botox 100 unit", "unit": "vial" }, { "cost": "852.0", "description": "Dysport 500 unit vial", "unit": "vial" }, { "cost": "1260.0", "description": "Botox 200 unit vial", "unit": "vial" } ]

[ { "approved": "2005-11-15", "country": "Canada", "expires": "2019-08-20", "number": "2280565" }, { "approved": "2001-05-15", "country": "Canada", "expires": "2014-06-07", "number": "2310845" } ]

[ "Botox", "Botox", "Botox", "BOTOX Cosmetic", "BOTOX Cosmetic", "Dysport", "Dysport Aesthetic", "Dysport Therapeutic", "Dysport Therapeutic", "Nuceiva", "Nuceiva", "Nuceiva", "Nuceiva", "Nuceiva", "Xeomin", "Xeomin", "Xeomin Cosmetic" ]

[]

[ "P60880", "P62745" ]

[]

[ "P02768" ]

[]

DB00085

Pancrelipase

Pancrelipase, in general, is composed of a mixture of pancreatic enzymes which include amylases, lipases, and proteases. These enzymes are extracted from porcine pancreatic glands.[L2509] The pancrelipase mixture was developed by Ortho-McNeil-Janssen Pharmaceuticals, Inc and FDA approved on April 12, 2010.[L2510] For further information on the components of this mixture please visit [DB11065], [DB11066] and [DB13147].

solid

The use of pancrelipase amylase is part of the pancreatic enzyme replacement therapy. This therapy is indicated for the treatment of pancreatic insufficiency attributed to cystic fibrosis, chronic pancreatitis or any other medically defined pancreatic disease that might require it.[A32721, A32736] Pancreatic diseases are associated with the deterioration of pancreatic parenchyma and of the dual physiological functions of the pancreas. Once established, pancreatic insufficiency results in malnutrition, weight loss, and steatorrhea.[A32723]

The major maldigestion/malabsorption problems arise from incomplete fat digestion. In clinical trials, the administration of pancrelipase as a mixture of amylase, lipase, and protease demonstrated a significant improvement in the coefficient of fat absorption and nitrogen absorption. These effects are accompanied by increased in body weight and body mass index.[A32721]

Pancrelipase is used to replace the deficiency of pancreatic enzymes. As abovementioned, pancrelipase is formed by a mixture of lipase, protease, and amylase which are able to break down fat, protein, and starches, respectively, in the small intestine.[T180] For a more specific description of each mechanism of action, please visit [DB11065], [DB11066] and [DB13147].

Pancrelipase acts locally in the GI tract and it is not absorbed in any significant amount.[L2521]

Pancrelipase acts locally in the GI tract and it is not absorbed in any significant amount thus, the metabolism is not relevant.[L2521]

The studies of the toxicology of pancrelipase are not needed as this drug has been used clinically for a long time.[L1770] Clinical overdose studies proved no effect on lungs, pancreas, liver and kidneys but it can produce symptoms such as diarrhea or stomach upset. Carcinogenicity studies have not shown any increased incidence with the use of pancrelipase. As pancrelipase is not absorbed, the effect on fetal development or reproduction is not expected.[L2528]

Pancrelipase acts locally in the GI tract and it is not absorbed in any significant amount thus, the elimination half-life is not relevant.[L2521]

Pancrelipase acts locally in the GI tract and it is not absorbed in any significant amount thus, the protein binding is not relevant.[L2521]

Pancrelipase is entirely eliminated in the feces.[L2521]

Pancrelipase acts locally in the GI tract and it is not absorbed in any significant amount thus, the volume of distribution is not relevant.[L2521]

Pancrelipase acts locally in the GI tract and it is not absorbed in any significant amount thus, the clearance rate is not relevant.[L2521]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "A09AA", "A09A", "A09", "A" ]

[ "Humans and other mammals" ]

[ { "cost": "1.03", "description": "Pancrelipase MST-16 48-16-48mu Enteric Coated Capsule", "unit": "capsule" }, { "cost": "1.38", "description": "Pancrelipase 10000 30-10-30mu Enteric Coated Capsule", "unit": "capsule" }, { "cost": "1.49", "description": "Pancrease MT 10 30-10-30mu Enteric Coated Capsule", "unit": "capsule" }, { "cost": "1.54", "description": "Creon 10 33.2-10-37.5mu Enteric Coated Capsule", "unit": "capsule" }, { "cost": "1.65", "description": "Ultrase MT 12 39-12-39mu Enteric Coated Capsule", "unit": "capsule" }, { "cost": "2.02", "description": "Pancrelipase 16000 48-16-48mu Enteric Coated Capsule", "unit": "capsule" }, { "cost": "2.4", "description": "Pancrease MT 16 48-16-48mu Enteric Coated Capsule", "unit": "capsule" }, { "cost": "2.65", "description": "Ultrase MT 18 58.5-18-58.5mu Enteric Coated Capsule", "unit": "capsule" }, { "cost": "2.83", "description": "Creon 20 66.4-20-75mu Enteric Coated Capsule", "unit": "capsule" }, { "cost": "2.99", "description": "Pancrease MT 20 56-20-44mu Enteric Coated Capsule", "unit": "capsule" }, { "cost": "3.06", "description": "Ultrase MT 20 65-20-65mu Enteric Coated Capsule", "unit": "capsule" }, { "cost": "3.32", "description": "Creon 24000 unit Enteric Coated Capsule", "unit": "capsule" }, { "cost": "0.64", "description": "Pancrelipase ec 4500 capsule", "unit": "capsule" }, { "cost": "0.76", "description": "Pancrease ec capsule", "unit": "capsule" }, { "cost": "0.8", "description": "Ultrase 4500 unit Enteric Coated Capsule", "unit": "capsule" }, { "cost": "0.86", "description": "Creon 5 16.6-5-18.75mu Enteric Coated Capsule", "unit": "capsule" }, { "cost": "0.87", "description": "Pancrease 4500 unit Enteric Coated Capsule", "unit": "capsule" } ]

[ { "approved": "2015-12-01", "country": "United States", "expires": "2030-02-07", "number": "9198871" }, { "approved": "2013-10-22", "country": "United States", "expires": "2028-02-20", "number": "8562979" }, { "approved": "2013-10-22", "country": "United States", "expires": "2028-02-20", "number": "8562980" }, { "approved": "2013-10-22", "country": "United States", "expires": "2028-02-20", "number": "8562981" }, { "approved": "2012-07-17", "country": "United States", "expires": "2028-02-20", "number": "8221747" }, { "approved": "2013-10-22", "country": "United States", "expires": "2028-02-20", "number": "8562978" }, { "approved": "2012-08-21", "country": "United States", "expires": "2028-02-20", "number": "8246950" }, { "approved": "2010-02-09", "country": "United States", "expires": "2028-02-20", "number": "7658918" } ]

[ "Alka-pan Tablets", "Bio-zyme Tab 50mg", "Duchol Ect", "Dygest", "Enzyme Tablets", "Festal Plus", "Festal Plus", "Medichol", "Neo Life Enzyme Tab", "Pancreatin and Enzyme Formula - Tablet", "Pancreatin Tab 400mg", "Pancreatine Enzymes", "Pancrelipase HP", "Pancrex Granules", "Pancrex V Capsules", "Pancrex V Forte Tablets 1gm/tab", "Pancrex V Powder", "Pancrex V Tab 0.33gm", "Phytozyme Tab 150mg", "Pro Gest Tab", "Stozyme", "Zypanax" ]

[ "Cotazym", "Ku-Zyme", "Pancrease", "Ultrase", "Ultresa (delayed-release enteric coated capsules)", "Viokace (tablets)", "Zymase" ]

[ "Festal Plus", "Stozyme", "Pro Gest Tab", "Medichol", "Duchol Ect", "Neo Life Enzyme Tab", "Pancreatin and Enzyme Formula - Tablet", "Enzyme Tablets", "Pancreatine Enzymes", "Dygest", "Zypanax", "Alka-pan Tablets", "Festal Plus" ]

[]

DB00086

Streptokinase

Streptokinase, is a sterile, purified preparation of a bacterial protein elaborated by group C (beta) -hemolytic streptococci.

liquid

For the treatment of acute evolving transmural myocardial infarction, pulmonary embolism, deep vein thrombosis, arterial thrombosis or emolism and occlusion of arteriovenous cannulae

Streptokinase creates an active complex which promotes the cleavage of the Arg/Val bond in plasminogen to form the proteolytic enzyme plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action. This helps eliminate blood clots or arterial blockages that cause myocardial infarction.

Plasminogen is an inactive molecule that becomes activated to plasmin when the Arg/Val bond is cleaved. Plasmin breaks down fibrin clots created by the blood clotting cascade. Streptokinase forms a highly specific 1:1 enzymatic complex with plasminogen which converts inactive plasminogen molecules into active plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins. This in turn leads to the degradation of blood clots.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "B01AD", "B01A", "B01", "B", "B06AA", "B06A", "B06", "B" ]

[ "Humans and other mammals" ]

[]

[ "Kabikinase - Pws 1500000units/vial", "Kabikinase - Pws 250000 Unit/vial", "Kabikinase - Pws 750000units/vial", "Streptase", "Streptase", "Streptase", "Streptase Inj 1500000 Unit/vial", "Streptase Inj 250000unit/vial", "Streptase Inj 750000unit/vial" ]

[]

[ "P00747", "P25116" ]

[ "P47712" ]

[]

DB00087

Alemtuzumab

Alemtuzumab is a humanized monoclonal antibody specific to lymphocyte antigens. It is a recombinant DNA-derived humanized monoclonal antibody (Campath-1H) that is directed against the 21-28 kD cell surface glycoprotein, CD52. The Campath-1H antibody is an IgG1 kappa with the human variable framework and constant regions, and complementarity-determining regions from a murine (rat) monoclonal antibody (Campath-1G). Alemtuzumab is produced in mammalian cell (Chinese hamster ovary) suspension culture in a medium containing neomycin.[L43397] Alemtuzumab was approved by the FDA in 2001.[L43397] It is marketed as LEMTRADA for multiple sclerosis (MS) treatment and CAMPTAH for B-cell chronic lymphocytic leukemia (B-CLL). The dose of alemtuzumab used for B-CLL is much higher than that for MS, and also at more frequent dosing.[L43397, L30335]

liquid

LEMTRADA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), including relapsing-remitting disease and active secondary progressive disease, in adults. Because of its safety profile, the use of LEMTRADA should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.[L43397] LEMTRADA contains the same active ingredient (alemtuzumab) found in CAMPATH, and CAMPATH is approved for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), although generally administered at higher and more frequent doses (e.g., 30 mg) than recommended in the treatment of MS.[L43397]

Alemtuzumab depletes circulating T and B lymphocytes after each treatment course. In clinical trials, the lowest cell counts occurred 1 month after a course of treatment at the time of the first post-treatment blood count. Lymphocyte counts then increased over time: B cell counts usually recovered within 6 months; T cell counts increased more slowly and usually remained below baseline 12 months after treatment. Approximately 60% of patients had total lymphocyte counts below the lower limit of normal 6 months after each treatment course and 20% had counts below the lower limit of normal after 12 months.[L43397] Reconstitution of the lymphocyte population varies for the different lymphocyte subtypes. At Month 1 in clinical trials, the mean CD4+ lymphocyte count was 40 cells per microliter, and, at Month 12, 270 cells per microliter. At 30 months, approximately half of patients had CD4+ lymphocyte counts that remained below the lower limit of normal.[L43397]

The precise mechanism by which alemtuzumab exerts its therapeutic effects in multiple sclerosis is unknown but is presumed to involve binding to CD52, a cell surface antigen present on T and B lymphocytes, and on natural killer cells, monocytes, and macrophages. Following cell surface binding to T and B lymphocytes, alemtuzumab results in antibody-dependent cellular cytolysis and complement-mediated lysis.[L43397] Research suggests that alemtuzumab can also exert immunomodulatory effects through the depletion and repopulation of lymphocytes, including alterations in the number, proportions, and properties of some lymphocyte subsets posttreatment, increasing representation of regulatory T cell subsets, and increasing representation of memory T- and B-lymphocytes.[L43418] The reduction in the level of circulating B and T cells by alemtuzumab and subsequent repopulation may reduce the potential for relapse, which ultimately delays disease progression.[L43418,L30335]

Serum concentrations increased with each consecutive dose within a treatment course, with the highest observed concentrations occurring following the last infusion of a treatment course. The mean maximum concentration was 3014 ng/mL on Day 5 of the first treatment course, and 2276 ng/mL on Day 3 of the second treatment course.[L43397]

null

LEMTRADA induces persistent thyroid disorders [see Warnings and Precautions (5.8)]. Untreated hypothyroidism in pregnant women increases the risk of miscarriage and may have effects on the fetus including mental retardation and dwarfism. In mothers with Graves’ disease, maternal thyroid stimulating hormone receptor antibodies can be transferred to a developing fetus and can cause neonatal Graves’ disease. In a patient who developed Graves’ disease after treatment with alemtuzumab, placental transfer of anti-thyrotropin receptor antibodies resulted in neonatal Graves’ disease with thyroid storm in her infant who was born 1 year after alemtuzumab dosing.[L43397] When LEMTRADA was administered to pregnant huCD52 transgenic mice during organogenesis (gestation days [GD] 6-10 or GD 11-15) at doses of 3 or 10 mg/kg IV, no teratogenic effects were observed. However, there was an increase in embryo lethality (increased postimplantation loss and the number of dams with all fetuses dead or resorbed) in pregnant animals dosed during GD 11-15. In a separate study in pregnant huCD52 transgenic mice, administration of LEMTRADA during organogenesis (GD 6-10 or GD 11-15) at doses of 3 or 10 mg/kg IV, decreases in B- and T-lymphocyte populations were observed in the offspring at both doses tested.[L43397] In pregnant huCD52 transgenic mice administered LEMTRADA at doses of 3 or 10 mg/kg/day IV throughout gestation and lactation, there was an increase in pup deaths during the lactation period at 10 mg/kg. Decreases in T- and B-lymphocyte populations and in antibody response were observed in offspring at both doses tested.[L43397] Before initiation of LEMTRADA treatment, women of childbearing potential should be counseled on the potential for serious risk to the fetus. To avoid in-utero exposure to LEMTRADA, women of childbearing potential should use effective contraceptive measures when receiving a course of treatment with LEMTRADA and for 4 months following that course of treatment.[L43397] In huCD52 transgenic mice, administration of LEMTRADA prior to and during the mating period resulted in adverse effects on sperm parameters in males and a reduced number of corpora lutea and implantations in females.[L43397] Two MS patients experienced serious reactions (headache, rash, and either hypotension or sinus tachycardia) after a single accidental infusion of up to 60 mg of LEMTRADA. Doses of LEMTRADA greater than those recommended may increase the intensity and/or duration of infusion reactions or their immune effects. There is no known antidote for alemtuzumab overdosage.[L43397]

The elimination half-life was approximately 2 weeks and was comparable between courses. The serum concentrations were generally undetectable (<60 ng/mL) within approximately 30 days following each treatment course.[L43397]

null

Alemtuzumab is a large-molecule monoclonal antibody and as such, it is cleared primarily through target-mediated clearance and through simple non-target specific IgG clearance mechanisms. Alemtuzumab is not excreted renally or eliminated via cytochrome P450 (CYP450) isoenzymes.[L43418] Alemtuzumab is most likely removed by opsonization via the reticuloendothelial system when bound to B or T lymphocytes.[A134]

Alemtuzumab is largely confined to the blood and interstitial space with a central volume of distribution of 14.1 L.[L43397]

Clearance of alemtuzumab ranged from 0.012 – 0.096 l/h depending on the study, dose group, and anti-alemtuzumab antibody status. The inter-subject variability for clearance was large (58 %). Higher clearance values were observed in cycle 1 compared to cycle 2, with the decrease in clearance from cycle 1 to cycle 2 being less than 20%.[L43418]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "L04AG", "L04A", "L04", "L" ]

[]

[ { "cost": "2042.18", "description": "Campath 30 mg/ml vial", "unit": "ml" }, { "cost": "6179.24", "description": "Campath 30 mg/ml Solution (1 Box Contains Three 1ml Vials)", "unit": "box" } ]

[ { "approved": "1997-08-05", "country": "Canada", "expires": "2014-08-05", "number": "1339198" } ]

[ "Campath", "Campath", "Lemtrada", "Lemtrada", "Lemtrada", "Mabcampath", "Mabcampath" ]

[]

[ "P31358", "O75015", "P08637", "P12314", "P12318", "P31994", "P31995" ]

[]

DB00088

Alglucerase

Human Beta-glucocerebrosidase or Beta-D-glucosyl-N-acylsphingosine glucohydrolase E.C. 3.2.1.45. 497 residue protein with N-linked carbohydrates, MW=59.3 kD. Alglucerase is prepared by modification of the oligosaccharide chains of human Beta-glucocerebrosidase. The modification alters the sugar residues at the non-reducing ends of the oligosaccharide chains of the glycoprotein so that they are predominantly terminated with mannose residues. Alglucerase was first approved by the FDA in 1991;[A254816] however, it was later discontinued from the market.

liquid

Alglucerase is indicated for use as a long-term enzyme replacement therapy in patients with Type I Gaucher disease who exhibit signs and symptoms that are severe enough to result in moderate-to-severe anemia, thrombocytopenia, bone disease, or significant hepato- or splenomegaly.[L44266]

Gaucher disease is characterized by a functional deficiency in Beta-glucocerebrosidase enzymatic activity and the resultant accumulation of lipid glucocerebroside in tissue macrophages which become engorged and are termed Gaucher cells. Gaucher cells are typically found in liver, spleen and bone marrow. This can lead to an enlarged spleen and liver (hepatosplenomegaly). Secondary hematologic sequelae include severe anemia and thrombocytopenia. Injections of alglucerase into Gaucher disease patients leads to elevated serum levels of the enzyme and reduction in the accumulation of glucocerebroside.

Alglucerase catalyzes the hydrolysis of the glycolipid, glucocerebroside, to glucose and ceramide as part of the normal degradation pathway for membrane lipids.

null

3.6-10.4 min

null

* 49.4 to 282.1 mL/kg

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational", "withdrawn" ]

[ "A16AB", "A16A", "A16", "A" ]

[ "Humans and other mammals" ]

[ { "cost": "380.64", "description": "Ceredase 80 unit/ml vial", "unit": "ml" } ]

[]

Alglucerase

[ "Ceredase" ]

[]

DB00089

Capromab pendetide

Capromab is a Murine IgG1 monoclonal 7E11-C5.3 antibody that recognizes prostate specific membrane antigen (PSMA – also known as glutamate carboxypeptidase 2) from prostate cancer cells and normal prostate tissue. When linked to pendetide, capromab is used as a chelating agent for the radionuclide [Indium In-111] during imaging to evaluate the extent of prostate cancer.

liquid

For diagnosis of prostate cancer and detection of intra-pelvic metastases.

Binds to the prostate-specific membrane antigen, which is a cell surface protein generally overexpressed in prostate tissues and prostate cancers. The radioactive Indium 111, which is covalently attached to the antibody, allows radiodiagnostic detection of PSMA expressing cells and tumors.

Binds selectively to cell-surface prostate-specific membrane antigen (PSMA) expressed on prostate tissues and tumors.

null

Most likely removed by opsonization via the reticuloendothelial system or by human antimurine antibody production

null

Approximately 10% of the administered radioisotope dose is excreted in the urine during the 72 hours following intravenous infusion.

* 4 ± 2.1 L

* 42 +/- 22 mL/hr

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "V09IB", "V09I", "V09", "V" ]

[ "Humans and other mammals" ]

[ { "cost": "1584.0", "description": "Prostascint kit", "unit": "kit" } ]

[]

[ "ProstaScint Kit for the Preparation of Indium In 111 Capromab Pendetide" ]

[ "ProstaScint" ]

[]

[ "Q04609" ]

[]

DB00090

Laronidase

Human recombinant alpha-L-iduronidase, 628 residues (mature form), produced by recombinant DNAtechnology in a Chinese hamster ovary cell line. Laronidase is a glycoprotein with a molecular weight of approximately 83 kD. The predicted amino acid sequence of the recombinant form, as well as the nucleotide sequence that encodes it, are identical to a polymorphic form of human a-L-iduronidase. It contains 6 N-linked oligosaccharide modification sites.

liquid

For the treatment of mucopolysaccharidosis

Laronidase is used to treat mucopolysaccharide storage disorders (specifically mucopolysaccharidosis 1 or Hurlers syndrome) caused by deficiencies of alpha-L-iduronidase. Reduced or absent a-L-iduronidase activity results in the accumulation of the GAG substrates, dermatan sulfate and heparan sulfate, throughout the body and leads to widespread cellular, tissue, and organ dysfunction.

Laronidase catalyses the hydrolysis of terminal alpha-L-iduronic acid residues of dermatan sulfate and heparin sulfate.

null

1.5-3.6 hrs

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "A16AB", "A16A", "A16", "A" ]

[ "Humans and other mammals" ]

[ { "cost": "168.0", "description": "Aldurazyme 2.9 mg/5 ml vial", "unit": "ml" } ]

[]

alpha-L-Idosiduronase | Human Recombinant alpha-L-iduronidase | Laronidasa | Laronidase | Laronidase (genetical recombination)

[ "Aldurazyme", "Aldurazyme", "Aldurazyme", "Aldurazyme", "Aldurazyme" ]

[]

DB00091

Cyclosporine

Cyclosporine is a calcineurin inhibitor known for its immunomodulatory properties that prevent organ transplant rejection and treat various inflammatory and autoimmune conditions. It is isolated from the fungus _Beauveria nivea_.[A174049] Initially manufactured by Sandoz and approved for use by the FDA in 1983, cyclosporine is now available in various products by Novartis (previously known as Sandoz).[L11097,L3734,L11118]

solid

Cyclosporine is approved for a variety of conditions. Firstly, it is approved for the prophylaxis of organ rejection in allogeneic kidney, liver, and heart transplants. It is also used to prevent bone marrow transplant rejection. For the above indications, cyclosporine can be used in conjunction with azathioprine and corticosteroids. Finally, cyclosporine can be used in patients who have chronic transplant rejection and have received previous immunosuppressive therapy[L3002] and to prevent or treat graft-versus-host disease (GVHD).[L11097] Secondly, cyclosporine is used for the treatment of patients with severe active rheumatoid arthritis (RA) when they no longer respond to methotrexate alone.[L3734] It can be used for the treatment of adult non-immunocompromised patients with severe, recalcitrant, plaque psoriasis that have failed to respond to at least one systemic therapy or when systemic therapies are not tolerated or contraindicated.[L3734] The ophthalmic solution of cyclosporine is indicated to increase tear production in patients suffering from keratoconjunctivitis sicca.[L11097] In addition, cyclosporine is approved for the treatment of steroid dependent and steroid-resistant nephrotic syndrome due to glomerular diseases which may include minimal change nephropathy, focal and segmental glomerulosclerosis or membranous glomerulonephritis.[L11097] A cyclosporine ophthalmic emulsion is indicated in the treatment of vernal keratoconjunctivitis in adults and children.[L34694] Off-label, cyclosporine is commonly used for the treatment of various autoimmune and inflammatory conditions such as atopic dermatitis, blistering disorders, ulcerative colitis, juvenile rheumatoid arthritis, uveitis, connective tissue diseases, as well as idiopathic thrombocytopenic purpura.[A139,A174085,A189393,A189396,A189399]

Cyclosporine exerts potent immunosuppressive actions on T cells, thereby prolonging survival following organ and bone marrow transplants.[L3734] This drug prevents and controls serious immune-mediated reactions including allograft rejection, graft versus host disease, and inflammatory autoimmune disease.[L3734] Some notable effects of cyclosporine are hypertrichosis, gingival hyperplasia, and hyperlipidemia. There is also some debate about this drug causing nephrotoxicity.[A189402]

Cyclosporine is a calcineurin inhibitor that inhibits T cell activation.[A174049,A174088,A189411] Its binding to the receptor cyclophilin-1 inside cells produces a complex known as cyclosporine-cyclophilin. This complex subsequently inhibits calcineurin, which in turn stops the dephosphorylation as well as the activation of the nuclear factor of activated T cells (NF-AT) that normally cause inflammatory reactions. NF-AT is a transcription factor that promotes the production of cytokines such as IL-2, IL-4, interferon-gamma and TNF-alpha, all of which are involved in the inflammatory process. Specifically, the inhibition of IL-2, which is necessary for T cell activation or proliferation, is believed to be responsible for cyclosporine's immunosuppressive actions.[A174049,A189408] In addition to the above, the inhibition of NF-AT leads to lower levels of other factors associated with T helper cell function and thymocyte development.[A174049]

The absorption of cyclosporine occurs mainly in the intestine.[A174049,A189405] Absorption of cyclosporine is highly variable with a peak bioavailability of 30% sometimes occurring 1-8 hours after administration with a second peak observed in certain patients.[A174088,L11097] The absorption of cyclosporine from the GI tract has been found to be incomplete, likely due to first pass effects.[A189402] Cmax in both the blood and plasma occurs at approximately 3.5 hours post-dose.[L3002] The Cmax of a 0.1% cyclosporine ophthalmic emulsion is 0.67 ng/mL after instilling one drop four times daily.[L34694] A note on erratic absorption During chronic administration, the absorption of Sandimmune Soft Gelatin Capsules and Oral Solution have been observed to be erratic, according to Novartis prescribing information. Those being administered the soft gelatin capsules or oral solution over the long term should be regularly monitored by testing cyclosporine blood concentrations and adjusting the dose accordingly.[L3002] When compared with the other oral forms of Sandimmune, Neoral capsules and solution have a higher rate of absorption that results in a higher Tmax and a 59% higher Cmax with a 29 % higher bioavailability.[L3002]

Cyclosporine is metabolized in the intestine and the liver by CYP450 enzymes, predominantly CYP3A4 with contributions from CYP3A5.[A174049,A189402] The involvement of CYP3A7 is not clearly established.[A189402] Cyclosporine undergoes several metabolic pathways and about 25 different metabolites have been identified. One of its main active metabolites, AM1, demonstrates only 10-20% activity when compared to the parent drug, according to some studies.[A174088,A189402] The 3 primary metabolites are M1, M9, and M4N, which are produced from oxidation at the 1-beta, 9-gamma, and 4-N-demethylated positions, respectively.[A189402]

The oral LD50 in rats is 1480 mg/kg and the TDLO in humans is 12 mg/kg.[L11085] **Overdose information** In cases of overdose with oral cyclosporine, forced emesis and gastric lavage are recommended 2 hours after ingestion. There are little data available in the literature regarding overdoses with cyclosporine, but hepatotoxicity and nephrotoxicity may occur.[L3734] One case report of an cyclosporine overdose due to medical error was made involving a 26 year old female and noted the occurrence of nausea, flushing, tremor, vertigo and vomiting, which resolved within about 1 day. Anorexia and a feeling of increased body girth were also experienced by this patient and resolved within about 2 weeks.[A189453] When overdose with cyclosporine is observed, it is important to consider that dialysis and charcoal, hemoperfusion are not effective techniques to remove cyclosporine from the body.[L3734]

The half-life of cyclosporine is biphasic and very variable on different conditions but it is reported in general to last 19 hours.[A174088] Prescribing information also states a terminal half-life of approximately 19 hours, but with a range between 10 to 27 hours.[L3002]

About 50% of the administered dose is taken up by erythrocytes while about 34% is bound to lipoproteins.[A174088] Prescribing information for Sandimmune states that 90% is mainly bound to lipoproteins.[L3002]

After sulfate conjugation, cyclosporine remains in the bile where it is broken down to the original compound and then re-absorbed into the circulation. Cyclosporine excretion is primarily biliary with only 3-6%[A189402,L3002] of the dose (including the parent drug and metabolites) excreted in the urine while 90% of the administered dose is eliminated in the bile. From the excreted proportion, under 1% of the dose is excreted as unchanged cyclosporine.[A174088,L3002]

The distribution of cyclosporine in the blood consists of 33%-47% in plasma, 4%-9% in the lymphocytes, 5%-12% in the granulocytes, and 41%-58% in the erythrocytes.[L3002] The reported volume of distribution of cyclosporine ranges from 4-8 L/kg. It concentrates mainly in leucocyte-rich tissues as well as tissues that contain high amounts of fat because it is highly lipophilic.[A189402] Cyclosporine, in the eye drop formulation, crosses the blood-retinal barrier.[A174088,A189450]

Cyclosporin shows a linear clearance profile that ranges from 0.38 to 3 Lxh/kg[A174088], however, there is substantial inter- patient variability.[A189402] A 250 mg dose of cyclosporine in the oral soft gelatin capsule of a lipid micro-emulsion formulation shows an approximate clearance of 22.5 L/h.[A189453]

Organic compounds

Organic acids and derivatives

Peptidomimetics

Peptoid-peptide hybrids

[ "approved", "investigational", "vet_approved" ]

[ "L04AD", "L04A", "L04", "L", "S01XA", "S01X", "S01", "S" ]

[ "Humans and other mammals" ]

[ { "cost": "1.32", "description": "Gengraf 25 mg capsule", "unit": "capsule" }, { "cost": "1.38", "description": "Cyclosporine 25 mg softgel", "unit": "softgel capsule" }, { "cost": "1.53", "description": "Neoral 25 mg gelatin capsule", "unit": "capsule" }, { "cost": "1.56", "description": "Cyclosporine 25 mg capsule", "unit": "capsule" }, { "cost": "2.48", "description": "Sandimmune 25 mg capsule", "unit": "capsule" }, { "cost": "2.74", "description": "Cyclosporine 50 mg softgel", "unit": "softgel capsule" }, { "cost": "4.49", "description": "Restasis 0.05% eye emulsion", "unit": "each" }, { "cost": "5.28", "description": "Cyclosporine 50 mg/ml vial", "unit": "ml" }, { "cost": "5.28", "description": "Gengraf 100 mg capsule", "unit": "capsule" }, { "cost": "5.45", "description": "Cyclosporine 50 mg/ml amp", "unit": "ml" }, { "cost": "5.49", "description": "Cyclosporine modif 100 mg capsule", "unit": "capsule" }, { "cost": "5.5", "description": "Cyclosporine 100 mg softgel", "unit": "softgel capsule" }, { "cost": "5.5", "description": "Cyclosporine modif 100 mg softgel", "unit": "softgel capsule" }, { "cost": "6.11", "description": "Neoral 100 mg gelatn capsule", "unit": "capsule" }, { "cost": "6.46", "description": "Cyclosporine 100 mg capsule", "unit": "capsule" }, { "cost": "7.71", "description": "Sandimmune 50 mg/ml ampul", "unit": "ml" }, { "cost": "9.89", "description": "Sandimmune 100 mg capsule", "unit": "capsule" }, { "cost": "25.2", "description": "Cyclosporine a powder", "unit": "g" }, { "cost": "42.9", "description": "CycloSPORINE Modified 30 25 mg capsule Box", "unit": "box" }, { "cost": "42.99", "description": "Gengraf 30 25 mg capsule Box", "unit": "box" }, { "cost": "46.38", "description": "SandIMMUNE 50 mg/ml Solution 5ml Ampule", "unit": "ampule" }, { "cost": "47.69", "description": "Neoral 30 25 mg capsule Box", "unit": "box" }, { "cost": "77.33", "description": "SandIMMUNE 30 25 mg capsule Box", "unit": "box" }, { "cost": "159.94", "description": "Gengraf 30 100 mg capsule Box", "unit": "box" }, { "cost": "171.48", "description": "CycloSPORINE Modified 30 100 mg capsule Box", "unit": "box" }, { "cost": "190.54", "description": "Neoral 30 100 mg capsule Box", "unit": "box" }, { "cost": "205.99", "description": "Restasis 30 0.05% Emulsion 1 Box = 30 Containers", "unit": "box" }, { "cost": "308.69", "description": "SandIMMUNE 30 100 mg capsule Box", "unit": "box" }, { "cost": "311.53", "description": "CycloSPORINE Modified 100 mg/ml Solution 50ml Bottle", "unit": "bottle" }, { "cost": "346.14", "description": "Neoral 100 mg/ml Solution 50ml Bottle", "unit": "bottle" }, { "cost": "499.62", "description": "SandIMMUNE 100 mg/ml Solution 50ml Bottle", "unit": "bottle" } ]

[ { "approved": "1999-11-16", "country": "United States", "expires": "2014-09-26", "number": "5985321" }, { "approved": "1989-06-13", "country": "United States", "expires": "2009-08-02", "number": "4839342" }, { "approved": "2003-04-15", "country": "Canada", "expires": "2012-04-16", "number": "2108018" }, { "approved": "1994-09-27", "country": "Canada", "expires": "2011-09-27", "number": "1332150" }, { "approved": "2014-01-21", "country": "United States", "expires": "2024-08-27", "number": "8633162" }, { "approved": "2014-02-11", "country": "United States", "expires": "2024-08-27", "number": "8648048" }, { "approved": "2016-02-02", "country": "United States", "expires": "2024-08-27", "number": "9248191" }, { "approved": "2014-01-14", "country": "United States", "expires": "2024-08-27", "number": "8629111" }, { "approved": "2014-02-04", "country": "United States", "expires": "2024-08-27", "number": "8642556" }, { "approved": "2014-04-01", "country": "United States", "expires": "2024-08-27", "number": "8685930" }, { "approved": "2013-10-22", "country": "United States", "expires": "2032-04-16", "number": "8561859" }, { "approved": "2017-06-13", "country": "United States", "expires": "2034-02-07", "number": "9676525" }, { "approved": "2012-10-23", "country": "United States", "expires": "2031-02-25", "number": "8292129" }, { "approved": "2017-06-06", "country": "United States", "expires": "2034-05-11", "number": "9669974" }, { "approved": "2018-04-10", "country": "United States", "expires": "2033-08-23", "number": "9937225" }, { "approved": "2015-03-17", "country": "United States", "expires": "2033-08-23", "number": "8980839" }, { "approved": "2019-10-15", "country": "United States", "expires": "2033-08-23", "number": "10441630" }, { "approved": "2021-02-16", "country": "United States", "expires": "2037-02-28", "number": "10918694" }, { "approved": "2012-10-30", "country": "United States", "expires": "2027-11-03", "number": "8298568" }, { "approved": "2015-12-29", "country": "United States", "expires": "2026-01-27", "number": "9220694" }, { "approved": "2011-07-05", "country": "United States", "expires": "2026-01-27", "number": "7973081" }, { "approved": "2013-09-03", "country": "United States", "expires": "2026-01-27", "number": "8524779" }, { "approved": "2015-09-15", "country": "United States", "expires": "2029-06-02", "number": "9132071" }, { "approved": "2018-05-01", "country": "United States", "expires": "2026-01-27", "number": "9956289" }, { "approved": "2006-01-27", "country": "United States", "expires": "2026-01-27", "number": "11612658" }, { "approved": "2013-12-24", "country": "United States", "expires": "2030-12-13", "number": "8614178" }, { "approved": "2020-10-27", "country": "United States", "expires": "2037-09-22", "number": "10813976" }, { "approved": "2021-10-26", "country": "United States", "expires": "2038-11-20", "number": "11154513" }, { "approved": "2019-10-11", "country": "United States", "expires": "2039-10-11", "number": "11413323" }, { "approved": "2017-02-28", "country": "United States", "expires": "2037-02-28", "number": "11951153" }, { "approved": "2022-04-01", "country": "United States", "expires": "2042-04-01", "number": "12059449" } ]

[ "Apo-cyclosporine Oral Solution", "Aqua-stasis", "Cequa", "Cequa", "Cequa", "Cyclo-derm", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "CycloSPORINE", "CycloSPORINE", "CycloSPORINE", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine", "Cyclosporine A", "Cyclosporine Modified", "Cyclosporine Modified", "Cyclosporine Modified", "Cyclosporine Modified", "Cyclosporine Modified", "Cyclosporine Modified", "Cyclosporine Modified", "Cyclosporine Modified", "Cyclosporine Modified", "CycloSPORINE, Modfied", "CycloSPORINE, Modfied", "CycloSPORINE, Modfied", "Cyclosporine/Chondroitin PF", "Cyclosporine/Chondroitin Sulfate PF", "Gengraf", "Gengraf", "Gengraf", "Gengraf", "Gengraf", "Gengraf", "Gengraf", "Gengraf", "Hydro-stasis", "Ikervis", "Ikervis", "Ikervis", "Ikervis", "Ikervis", "Nail Cyclosporin-A", "Neoral", "Neoral", "Neoral", "Neoral", "Neoral", "Neoral", "Neoral", "Neoral", "Neoral", "PMS-cyclosporine", "PMS-cyclosporine", "PMS-cyclosporine", "Restasis", "Restasis", "Restasis", "Restasis", "Restasis", "Restasis MultiDose", "Restasis MultiDose", "Sandimmune", "Sandimmune", "Sandimmune", "Sandimmune", "Sandimmune Cap 50mg", "Sandimmune I.V.", "Sandimmune Oral Sol 100mg/ml", "Sandimmune Soft Gelatin Cap 100mg", "Sandimmune Soft Gelatine Cap 25mg", "Sandoz Cyclosporine", "Sandoz Cyclosporine", "Sandoz Cyclosporine", "Teva-cyclosporine", "Verkazia", "Verkazia", "Verkazia", "Verkazia", "Verkazia", "Verkazia", "Verkazia", "Vevye", "Vevye" ]

[ "Sangcya", "Verkazia" ]

[]

[ "P49069", "Q08209", "Q96LZ3", "P62937", "P30405" ]

[ "P33261", "P10635", "P20815", "P08684" ]

[]

[ "P08183", "O95342", "Q12908", "Q14973", "Q4U2R8", "Q5T3U5", "Q92887", "Q9UNQ0", "Q9Y6L6", "Q9NPD5" ]

DB00092

Alefacept

Immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 (LFA-3) linked to the Fc (hinge, CH2 and CH3 domains) portion of human IgG1. Produced by CHO cells, mW is 91.4 kD.

liquid

As an immunosuppressive drug, Alefacept can be used for treatment of moderate to severe chronic plaque psoriasis

Interferes with lymphocyte activation by specifically binding to the lymphocyte antigen, CD2, and inhibiting LFA-3/CD2 interaction. Activation of T lymphocytes involving the interaction between LFA-3 on antigen-presenting cells and CD2 on T lymphocytes plays a role in the pathophysiology of chronic plaque psoriasis. Also causes a reduction in subsets of CD2+ T lymphocytes as well as CD4+ and CD8+ T lymphocytes.

Inhibits T-lymphocyte activation and production by binding to the CD2 lymphocyte antigen.

Bioavailability after IM administration is 63%.

null

While it has been found to cross the placenta in monkeys, it is not yet known if it also diffuses into breast milk.

~270 hours

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational", "withdrawn" ]

[ "L04AA", "L04A", "L04", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "1190.4", "description": "Amevive 15 mg vial", "unit": "vial" } ]

[]

[ "Amevive", "Amevive" ]

[]

[ "P06729", "P08637", "O75015" ]

[]

DB00093

Felypressin

A synthetic nonapeptide comprising cysteinyl, phenylalanyl, phenylalanyl, glutaminyl, asparaginyl, cysteinyl, prolyl, lysyl, and glycinamide residues in sequence, with a disulfide bridge joining the two cysteine residues. Its antidiuretic effects are less than those of vasopressin. It is a non-catecholamine vasoconstrictor used in local anaesthetic injections for dental use, and is an ingredient of preparations that have been used for treatment of pain and inflammation of the mouth.

solid

For use as an alternative to adrenaline as a localising agent, provided that local ischaemia is not essential.

Felypressin is a synthetic analog of lypressin or vasopressin with a greater vasoconstrictor activity than antidiuretic action. It is used primarily as a hemostatic.

Felypressin binds to the vasopressin receptor V1a. This causes contraction of the smooth muscle in the vascular bed, especially capillaries, small arterioles and venules.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "experimental" ]

[]

[ "Humans and other mammals" ]

[]

[]

[ "Colupressine", "Octapressin" ]

[]

[ "P37288" ]

[]

DB00094

Urofollitropin

Urofollitropin is a urinary-derived follicle-stimulating hormone (FSH) that is extracted and purified from human urine samples. It consists of two non-covalently linked, non-identical glycoproteins designated as the alpha- and beta- subunits. The alpha- and beta- subunits have 92 and 111 amino acids. The alpha subunit is glycosylated at Asn 51 and Asn 78 while the beta subunit is glycosylated at Asn 7 and Asn 24. Urofollitropin is typically used injected subcutaneously in combination with human chorionic gonadotropin (hCG) to induce ovulation. Urofollitropin may also be used to cause the ovary to produce several follicles, which can then be harvested for use in gamete intrafallopian transfer (GIFT) or in vitro fertilization (IVF).

liquid

For treatment of female infertility

Used for the treatment of female infertility, urofollitropin or follicle stimulating hormone (FSH) stimulates ovarian follicular growth in women who do not have primary ovarian failure. FSH, the active component of urofollitropin is the primary hormone responsible for follicular recruitment and development.

FSH binds to the follicle stimulating hormone receptor which is a G-coupled transmembrane receptor. Binding of the FSH to its receptor seems to induce phosphorylation and activation of the PI3K (Phosphatidylinositol-3-kinase) and Akt signaling pathway, which is known to regulate many other metabolic and related survival/maturation functions in cells.

74%

null

Circulation half life of 3-4 hours, elimination half life of 35-40 hours

null

Via liver and kidneys

Time to peak in plasma: IM: 17 hours (single dose), 11 hours (multiple doses) SubQ: 21 hours (single dose), 10 hours (multiple doses)

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "vet_approved" ]

[ "G03GA", "G03G", "G03", "G" ]

[ "Humans and other mammals" ]

[ { "cost": "93.85", "description": "Bravelle 75 unit vial", "unit": "vial" }, { "cost": "103.85", "description": "Fertinex 75 unit Solution", "unit": "vial" } ]

[ { "approved": "1998-06-16", "country": "United States", "expires": "2015-06-16", "number": "5767067" } ]

[ "Bravelle", "Fertinorm Hp 150 - Pws Diluent Im Sc", "Fertinorm Hp 75 - Pws Diluent Im Sc", "Metrodin 75 I.U." ]

[ "Fertinex", "Metrodin" ]

[ "Fertinorm Hp 75 - Pws Diluent Im Sc", "Fertinorm Hp 150 - Pws Diluent Im Sc" ]

[ "P23945" ]

[]

DB00095

Efalizumab

Humanized IgG1 kappa isotype monoclonal antibody that binds to human CD11a. Efalizumab has a molecular weight of approximately 150 kilodaltons and is produced in a Chinese hamster ovary mammalian cell expression system in a nutrient medium containing the antibiotic gentamicin. The FDA approved efalizumab in 2003. It was later withdrawn in 2009 due to a potential risk of progressive multifocal leukoencephalopathy (PML).[L43797]

liquid

For the treatment of adult patients with moderate to severe chronic plaque psoriasis, who are candidates for phototherapy or systemic therapy.

Lymphocyte activation and trafficking to skin play a role in the pathophysiology of chronic plaque psoriasis. In psoriatic skin, ICAM-1 cell surface expression is upregulated on endothelium and keratinocytes. Raptiva inhibits the binding of LFA-1 to the intercellular adhesion molecule-1 (ICAM-1), thereby inhibiting the adhesion of leukocytes to other cell types.

Efalizumab binds to CD11a, a subunit of leukocyte function antigen-1 (LFA-1), which is expressed on all leukocytes. As a result efalizumab decreases cell surface expression of CD11a.

Average efalizumab bioavailability following subcutaneous administration was estimated at 30 to 50%.

null

5 days

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational", "withdrawn" ]

[ "L04AG", "L04A", "L04", "L" ]

[ "Humans and other mammals" ]

[]

[ "Raptiva", "Raptiva", "Raptiva", "Raptiva" ]

[ "Xanelim" ]

[]

[ "P20702", "P20701" ]

[]

DB00097

Choriogonadotropin alfa

Recombinant human chorionic gonadotropin with 2 subunits, alpha = 92 residues, beta = 145 residues, each with N-and O-linked carbohydrate moieties linked to ASN-52 and ASN-78 (on alpha subunit) and ASN-13, ASN-30, SER-121, SER-127, SER-132 and SER-138 (on beta subunit). The primary structure of the alpha-chain of r-hCG is identical to that of the alpha-chain of hCG, FSH and LH.

solid

For the treatment of female infertility

Choriogonadotropin alfa is used to treat female infertility, Choriogonadotropin alfa stimulates late follicular maturation and resumption of oocyte meiosis, and initiates rupture of the pre-ovulatory ovarian follicle. Ovidrel is an analogue of Luteinizing Hormone (LH) and binds to the LH/hCG receptor of the granulosa and theca cells of the ovary to effect these changes in the absence of an endogenous LH surge.

Choriogonadotropin alfa binds to the Follicle stimulating hormone receptor which results in ovulation in the absence of sufficient endogenous Luteinizing hormone.

The mean absolute bioavailability following a single subcutaneous injection to healthy female volunteers is about 40%.

null

The mean terminal half-life is about 29 ± 6 hours (initial half-life is 4.5 ± 0.5 hours).

null

One-tenth of the dose is excreted in the urine.

* 5.9 ± 1.0 L

* 0.29 +/- 0.04 L/h [healthy down-regulated females]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "G03GA", "G03G", "G03", "G" ]

[ "Humans and other mammals" ]

[ { "cost": "57.23", "description": "Pregnyl 10000 unit vial", "unit": "vial" }, { "cost": "60.7", "description": "Pregnyl 10000 unit Solution", "unit": "vial" }, { "cost": "93.22", "description": "Ovidrel 250 mcg/0.5ml Injectable 0.5ml Syringe", "unit": "syringe" }, { "cost": "113.99", "description": "Novarel 10000 unit vial", "unit": "vial" }, { "cost": "118.55", "description": "Novarel 10000 unit/10ml Solution 1 Vial = 10ml", "unit": "vial" } ]

[ { "approved": "1998-06-16", "country": "United States", "expires": "2015-06-16", "number": "5767251" }, { "approved": "2004-03-16", "country": "United States", "expires": "2021-03-16", "number": "6706681" } ]

[ "Chorionic Gonadotropin", "Chorionic Gonadotropin", "Chorionic Gonadotropin", "Ovidrel", "Ovidrel", "Ovidrel", "Ovitrelle", "Ovitrelle", "Pregnyl", "Pregnyl", "Pregnyl", "Pregnyl", "Pregnyl" ]

[ "Profasi" ]

[]

[ "P23945", "P22888" ]

[]

DB00098

Antithymocyte immunoglobulin (rabbit)

Rabbit anti-thymocyte globulin. Thymoglobulin is a polyclonal antibody that suppresses certain types of immune cells responsible for acute organ rejection in transplant patients. Thymoglobulin is a mixture of antibodies intended to bind to various cell surface antigens. The most common mode of action of Thymoglobulin is via selective depletion of T-cells.

liquid

For prevention of renal transplant rejection

Antithymocyte Globulin (ATG) is a concentrated anti-human T-lymphocyte immunoglobulin preparation derived from rabbits after immunization with a T-lympoblast cell line. ATG is an immunosuppressive product for the prevention and treatment of acute rejection following organ transplantation. ATG reduces the host immune response against tissue transplants or organ allografts.

Binds to multiple, T-cell specific antigens leading to T-lymphocyte cell death via complement mediated cytotoxicity or apoptosis.

T-cell depletion usually observed within 1 day after initiating therapy. Average 21.5 and 87 mcg/mL 4–8 hours post-infusion after first and last IV doses, respectively, when given for 7–11 days.

Most likely removed by opsonization via the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production.

Not known whether ATG (rabbit) distributes into human milk; however, other immunoglobulins are distributed into human milk.

2-3 days, may increase after multiple doses administration

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "L04AA", "L04A", "L04", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "636.48", "description": "Thymoglobulin 25 mg vial", "unit": "vial" } ]

[]

[ "Thymoglobulin", "Thymoglobulin" ]

[ "ATG-Fresenius", "ATG-Fresenius S" ]

[]

[ "Q95460", "P20701", "P42081", "P31994", "P01730", "P05556", "P06756", "P05106", "P06126" ]

[]

DB00099

Filgrastim

Filgrastim is a short-acting recombinant, non-pegylated human granulocyte colony-stimulating factor (G-CSF) analog produced by recombinant DNA technology. It has an amino acid sequence identical to endogenous G-CSF, but it is non-glycosylated unlike the endogenous G-CSF and has an N-terminal methionine added in the sequence for expression in _E. Coli_.[L40714] Human G-CSF is a glycoprotein that regulates the production and release of neutrophils from the bone marrow. Filgrastim mimics the biological actions of G-CSF to increase the levels of neutrophils in the blood.[L40719] It has a number of therapeutic uses, including the management and prevention of infections and febrile neutropenia in patients receiving myelosuppressive chemotherapy or radiation therapy. It is also used to manage severe chronic neutropenia and mobilize hematopoietic progenitor cells to the peripheral blood for collection by leukapheresis in patients undergoing peripheral blood progenitor cell collection and therapy.[L40714] Filgrastim was approved in the US in 1991 and there are biosimilars available with similar therapeutic indications.[A245858] Tbo-filgrastim was approved by the FDA on August 29, 2012.[L36325] Filgrastim-sndz was approved on March 6, 2015 [L40768] and filgrastim-ayow was approved on March 2, 2022.[L40773] A long-acting, pegylated G-CSF, [pegfilgrastim], was made available to increase the duration of action of the drug.

liquid

Filgrastim is indicated to decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever.[L40714] Filgrastim is indicated for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia.[L40714] Filgrastim is indicated to reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation.[L40714] Filgrastim is indicated for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis.[L40714] Filgrastim is indicated for chronic administration to reduce the incidence and duration of sequelae of neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia.[L40714] Filgrastim is indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation.[L40714]

Filgrastim is used to reduce the incidence, severity and duration of neutropenia and febrile neutropenia in patients undergoing cytotoxic chemotherapy. In clinical trials in patients, filgrastim reduced the duration of febrile neutropenia, antibiotic use, and hospitalization after induction chemotherapy for acute myelogenous leukemia or myeloablative therapy followed by bone marrow transplantation; however, the incidence of fever and documented infections were not reduced in either setting.[L40719] Filgrastim is also used to mobilize hematopoietic progenitor cells into the peripheral blood in order to reduce the risk for bleeding complications and the need for platelet transfusions. Recipients of allogeneic PBPCs mobilized with filgrastim experienced significantly more rapid hematological recovery, leading to a significant decrease in time to unsupported platelet recovery when compared with allogeneic bone marrow transplantation.[L40719] Filgrastim causes a dose-dependent increase in circulating neutrophil counts within 24 hours of administration. Filgrastim can also cause a minor increase in monocyte and lymphocyte counts, but the clinical significance of these effects is unknown.[L40714] In some patients, filgrastim also caused a minor increase in the number of circulating eosinophils and basophils relative to baseline; however, these patients may already have had elevated eosinophils and basophils prior to filgrastim treatment. Following termination of filgrastim therapy, circulating neutrophil counts decrease by 50% within one to two days, and to normal levels within one to seven days. As with other hematopoietic growth factors, G-CSF has shown _in vitro_ stimulating properties on human endothelial cells.[L40719]

Neutrophils are critical granulocytes involved in the acute inflammatory response and host defences against bacterial infections.[A245873] They also contribute to long-term adaptive immunity by promoting immediate host immune response and attracting other cells, such as macrophages and dendritic cells. As neutrophils promote both the initiation and the maintenance of inflammation at sites of infection, suppressed neutrophil responses lead to extreme susceptibility to infection.[A35605] Low neutrophil levels, or neutropenia, caused by chronic neutropenia, myelosuppressive chemotherapy, and radiation therapy increases the risk of infection and related events.[A245868] Neutropenia caused by chemotherapy or radiation therapy can further progress into febrile neutropenia, which is associated with an elevated risk for life-threatening systemic infections and chemotherapy-associated morbidity and mortality.[A35591] The production and release of functional neutrophils from the bone marrow are normally regulated by granulocyte colony-stimulating factors (G-CSF), which are major cytokine regulators of neutrophilic granulocytes.[A35605] G-CSFs act on hematopoietic cells by binding to specific cell surface receptors to stimulate the proliferation‚ differentiation‚ and maturation of neutrophil progenitors. G-CSF also induces some end-cell functional activation of neutrophils, including enhanced phagocytic ability‚ priming of the cellular metabolism associated with respiratory burst‚ antibody-dependent killing, and the increased expression of some cell surface antigens.[L40714] Filgrastim is a short-acting recombinant G-CSF that mimics the biological actions of endogenous G-CSF. It also facilitates the release of neutrophils from the bone marrow into the blood to reduce the incidence of infection and manage neutropenia.[A245858, A245868]

Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70%.[L40714]

Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive.[A187841, A245878]

The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.[L40734] There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day.[L40714]

After intravenous administration, the elimination half-life of filgrastim was approximately 3.5 hours in both normal subjects and patients with cancer. Single parenteral doses or daily intravenous doses‚ over a 14-day period‚ resulted in comparable half-lives. The half-lives were similar for intravenous administration (231 minutes‚ following doses of 34.5 mcg/kg) and for subcutaneous administration (210 minutes‚ following filgrastim dosages of 3.45 mcg/kg).[L40714]

There is limited information available.

There is limited information available; however, filgrastim is subject to renal elimination.[A245878]

After intravenous administration, the volume of distribution averaged 150 mL/kg.[L40714] There is no evidence of drug accumulation.[L40719]

Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration.[L40714]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "L03AA", "L03A", "L03", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "286.04", "description": "Neupogen 300 mcg/ml vial", "unit": "vial" }, { "cost": "437.94", "description": "Neupogen 480 mcg/1.6 ml vial", "unit": "ml" }, { "cost": "3138.1", "description": "Neupogen 300 mcg/0.5ml Solution 1 Box Contains Ten 0.5ml Syringes", "unit": "box" }, { "cost": "4554.58", "description": "Neupogen 480 mcg/1.6ml Solution 1 Box Contains Ten 1.6ml Syringes", "unit": "box" }, { "cost": "4998.24", "description": "Neupogen 480 mcg/0.8ml Solution 1 Box Contains Ten 0.8ml Syringes", "unit": "box" } ]

[ { "approved": "2007-07-31", "country": "Canada", "expires": "2024-07-31", "number": "1341537" }, { "approved": "1997-07-29", "country": "Canada", "expires": "2014-07-29", "number": "1339071" } ]

[ "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Accofil", "Biograstim", "Biograstim", "Biograstim", "Biograstim", "Biograstim", "Biograstim", "Biograstim", "Biograstim", "Biograstim", "Biograstim", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Hexal", "Filgrastim Ratiopharm", "Filgrastim Ratiopharm", "Filgrastim Ratiopharm", "Filgrastim Ratiopharm", "Filgrastim Ratiopharm", "Filgrastim Ratiopharm", "Filgrastim Ratiopharm", "Filgrastim Ratiopharm", "Granix", "Granix", "Granix", "Granix", "Grastofil", "Grastofil", "Grastofil", "Grastofil", "Grastofil", "Grastofil", "Neupogen", "Neupogen", "Neupogen", "Neupogen", "Neupogen", "Neupogen", "Neupogen", "Neupogen", "Neupogen", "Neupogen", "Nivestim", "Nivestim", "Nivestim", "Nivestim", "Nivestim", "Nivestim", "Nivestim", "Nivestim", "Nivestim", "Nivestim", "Nivestim", "Nivestim", "Nivestym", "Nivestym", "Nivestym", "Nivestym", "Nivestym", "Nivestym", "Nivestym", "Nivestym", "Nypozi", "Nypozi", "NYPOZI txid", "NYPOZI txid", "Ratiograstim", "Ratiograstim", "Ratiograstim", "Ratiograstim", "Ratiograstim", "Ratiograstim", "Ratiograstim", "Ratiograstim", "Ratiograstim", "Ratiograstim", "Ratiograstim", "Ratiograstim", "Releuko", "Releuko", "Releuko", "Releuko", "Tevagrastim", "Tevagrastim", "Tevagrastim", "Tevagrastim", "Tevagrastim", "Tevagrastim", "Tevagrastim", "Tevagrastim", "Tevagrastim", "Tevagrastim", "Tevagrastim", "Tevagrastim", "Tevagrastim", "Tevagrastim", "Zarxio", "Zarxio", "Zarxio", "Zarxio", "Zarxio", "Zarxio", "Zarzio", "Zarzio", "Zarzio", "Zarzio", "Zarzio", "Zarzio", "Zarzio", "Zarzio", "Zarzio", "Zarzio", "Zarzio", "Zarzio", "Zarzio", "Zarzio", "Zarzio", "Zarzio" ]

[ "Biocilin", "Biofigran", "Biofilgran", "Endufil", "Filatil", "Filgen", "Gran", "Granulokine", "Grimatin", "Inmunef", "Jiexin", "Leucogen", "Leucostim", "Macroleuco", "Neukine", "Neutromax", "Neutroval", "Recombicyte", "SciLocyte", "Tevagastrim", "White-C", "Zarzio" ]

[]

[ "Q99062" ]

[ "P08246" ]

[]

DB00100

Coagulation Factor IX (Recombinant)

Recombinant Coagulation Factor IX is a purified Factor IX glycoprotein produced by recombinant DNA technology. It has a primary amino acid sequence that is identical to the Ala148 allelic form of human factor IX, and has structural and functional characteristics similar to those of endogenous factor IX. It is not derived from human blood (unlike human Factor IX complex), and is instead produced by a genetically engineered Chinese hamster ovary (CHO) cell line that secretes recombinant Factor IX into cell medium that is then processed and purified for use as a pharmaceutical agent. Recombinant Factor IX is indicated for the control and prevention of bleeding episodes in adult and pediatric patients with congenital factor IX deficiency (Hemophilia B).

liquid

For treatment of hemophilia (Christmas disease).

Binds vitamin K and factor VIIIa. Cleaves the Arg-Ile bond in factor X to form active factor Xa. Plays a key role in blood coagulation and clotting. Injections of factor IX are used to treat hemophilia B, which is sometimes called Christmas disease. AlphaNine is injected to increase plasma levels of Factor IX and can temporarily correct this coagulation defect. The activated partial thromboplastin time (aPTT) is prolonged in people with hemophilia B. Treatment with factor IX concentrate may normalize the aPTT by temporarily replacing the factor IX. The administration of BeneFIX increases plasma levels of factor IX, and can temporarily correct the coagulation defect in these patients.

Coagulation Factor IX is an important protein in the process of hemostasis and normal blood clotting as it plays a key role within the coagulation cascade. It is located within the blood plasma as a zymogen, an antecedent to enzymatic function, in its inactivated state. Factor IX is dependent on the presence of Vitamin K, and is activated to a serine protease by the function of Coagulation Factor XIa. Factor XIa cleaves the peptide bond associated with protein activation in Factor IX, leaving Factor IX with two exposed chains, a light chain and a heavy chain. These two chains are held together by several disulfide bonds that reinforce the structure of Factor IX's activated form. After being activated, Factor IX forms a complex with calcium ions, membrane phospholipids and Coagulation Factor VIII to activate Coagulation Factor X. The activation of Factor X then performs a similarly integral step in the blood coagulation cascade. The ultimate result of phenotypically normal coagulation factors is the creation of platelets for normal blood clotting.

null

18.8 ± 5.4 hours

null

8.62 ± 1.7

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[]

[ "Humans and other mammals" ]

[ { "cost": "1.0", "description": "Benefix 1000 unit vial", "unit": "vial" }, { "cost": "1.0", "description": "Benefix 250 unit vial", "unit": "vial" }, { "cost": "1.0", "description": "Benefix 500 unit vial", "unit": "vial" }, { "cost": "1.12", "description": "Benefix 2000 unit vial", "unit": "vial" }, { "cost": "1.2", "description": "Mononine 1000 unit vial", "unit": "vial" }, { "cost": "1.2", "description": "Mononine 500 unit vial", "unit": "vial" }, { "cost": "1.42", "description": "Alphanine sd 250-1500 unit vial", "unit": "vial" } ]

[]

[ "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "Benefix", "Benefix", "Benefix", "Benefix", "Benefix", "Benefix", "Benefix - (250iu)", "Benefix - (500iu)", "Benefix -(1000iu)", "Idelvion", "Idelvion", "Idelvion", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Ixinity", "Rebinyn", "Rebinyn", "Rebinyn", "Rebinyn", "Rixubis", "Rixubis", "Rixubis", "Rixubis", "Rixubis", "Rixubis", "Rixubis", "Rixubis", "Rixubis", "Rixubis", "Rixubis", "Rixubis", "Rixubis", "Rixubis", "Rixubis" ]

[]

[ "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "BeneFIX", "Benefix - (250iu)", "Benefix - (500iu)", "Benefix -(1000iu)" ]

[ "P00742", "P03951", "P08709", "P00451", "P00734", "Q07954", "P38435" ]

[]

DB00102

Becaplermin

Becaplermin is produced by recombinant DNA technology by insertion of the gene for the B chain of platelet derived growth factor (PDGF) into the yeast, Saccharomyces cerevisiae. Becaplermin has a molecular weight of approximately 25 KD and is a homodimer composed of two identical polypeptide chains that are bound together by disulfide bonds.

liquid

For topical treatment of skin ulcers (from diabetes)

Used for the topical treatment of skin ulcers, Regranex has a biological activity similar to that of endogenous platelet-derived growth factor, which includes promoting the chemotactic recruitment and proliferation of cells involved in wound repair and enhancing the formation of granulation tissue.

Binds to the beta platelet-derived growth factor (PDGF) receptor, a tyrosine kinase receptor. PDGF is known to exist as a dimer, and activates its signaling pathway by a ligand induced receptor dimerization and autophosphorylation. PDGF receptors also contain many auto-phosphorylation sites, which serve to mediate binding of SH2 sites and subsequently signal corresponding pathways. There are five different isoforms of PDGF that activate through two different receptors (alpha and beta).

very little systemic absorption. 15% of patients experienced complete healing within 8 weeks, while for 25% of patients, it was at 10 weeks.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "D03AX", "D03A", "D03", "D", "A01AD", "A01A", "A01", "A" ]

[ "Humans and other mammals" ]

[ { "cost": "46.4", "description": "Regranex 0.01% gel", "unit": "g" }, { "cost": "723.82", "description": "Regranex 0.01% Gel 15 gm Tube", "unit": "tube" } ]

[ { "approved": "1999-12-07", "country": "Canada", "expires": "2015-12-15", "number": "1340846" } ]

[ "Regranex", "Regranex", "Regranex", "Regranex", "Regranex (becaplermin) 0.01%" ]

[]

[ "P09619", "P16234", "P01023" ]

[]

DB00103

Agalsidase beta

Agalsidase beta is a recombinant human α-galactosidase A similar to [agalsidase alfa]. While patients generally do not experience a clinically significant difference in outcomes between the two drugs, some patients may experience greater benefit with agalsidase beta.[A220228,A220233] Use of agalsidase beta has decreased in Europe, in favor of agalsidase alfa, after a contamination event in 2009.[A220343] Agalsidase beta was granted FDA approval on 24 April 2003.[L16383]

liquid

Agalsidase beta is indicated in the treatment of Fabry disease.[L16383]

Agalsidase beta is a recombinant human α-galactosidase A used as enzyme replacement therapy in the treatment of Fabry disease.[L16398] It has a long duration of action and a wide therapeutic index.[L16383] Patients should be counselled regarding the risk of infusion related reactions and hypersensitivity.[L16383]

α-galactosidase A is uptaken by cells via the mannose 6 phosphate receptor.[A220323] Agalsidase beta hydrolyzes globotriaosylceramide and other glycosphingolipids that would normally be hydrolyzed by endogenous α-galactosidase A.[L16383] Preventing the accumulation of glycosphingolipids prevents or reduces the severity of manifestations of Fabry disease such as renal failure, cardiomyopathy, or cerebrovascular events.[L16383]

A 1 mg/kg dose of agalsidase beta with a mean infusion length of 115 minutes reaches a Cmax 5.0 ± 1.1 µg/mL with an AUC of 496 ± 137 µg\*min/mL.[L16383]

Data regarding the metabolism of agalsidase beta is not readily available.[L16383] However, protein drugs are expected to be degraded by proteases and other catalytic enzymes to smaller peptides and amino acids.[A182009]

Data regarding overdoses of agalsidase beta are not readily available.[L16383] Patients experiencing an overdose of agalsidase beta may experience an increased incidence and severity of adverse effects.[L16383] Overdose can be managed through the use of symptomatic and supportive measures.

agalsidase beta has a half like of 67 ± 12 min for a 1 mg/kg dose with a mean infusion length of 115 minutes.[L16383]

Data regarding the protein binding of agalsidase beta is not readily available.[L16383]

After nonspecific proteolysis, the amino acids from protein drugs are reused for protein synthesis or further broken down and eliminated by the kidneys.[A182009]

A 1 mg/kg dose of agalsidase beta with a mean infusion length of 115 minutes has a VSS of 112 ± 13 mL/kg.[L16383]

A 1 mg/kg dose of agalsidase beta with a mean infusion length of 115 minutes has a clearance of 2.1 ± 0.7 mL/min/kg.[L16383]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "A16AB", "A16A", "A16", "A" ]

[ "Humans and other mammals" ]

[ { "cost": "771.6", "description": "Fabrazyme 5 mg vial", "unit": "vial" }, { "cost": "5403.6", "description": "Fabrazyme 35 mg vial", "unit": "vial" } ]

[ { "approved": "2007-06-26", "country": "Canada", "expires": "2017-09-12", "number": "2265464" } ]

[ "Fabrazyme", "Fabrazyme", "Fabrazyme", "Fabrazyme", "Fabrazyme", "Fabrazyme", "Fabrazyme", "Fabrazyme", "Fabrazyme", "Fabrazyme" ]

[]

[ "P20645" ]

DB00104

Octreotide

Acromegaly is a disorder caused by excess growth hormone (GH), increasing the growth of body tissues and causing metabolic dysfunction.[L14501] In most cases, it results from an anterior pituitary growth hormone-releasing tumor. Typically, the feet, hands, and face grow abnormally large; organomegaly and insulin resistance may also occur. Acromegaly is a life-threatening disease requiring life-long management.[L14501] Octreotide is a long-acting drug with pharmacologic activities that mimic those of the natural hormone, somatostatin, which inhibits the secretion of growth hormone.[L14513] Additionally, it is used for the treatment of acromegaly and symptoms arising from various tumors, including carcinoid tumors and vasoactive intestinal tumors (VIPomas).[L14513] In the past, octreotide has been administered solely by injection. On June 26, 2020, the first approved delayed-release oral somatostatin analog, Mycapssa, received FDA approval for the long term maintenance treatment of acromegaly. This drug was developed by Chiasma Inc.[L14495,L14507,L14528]

solid

Octreotide by injection is used for the treatment of acromegaly and the reduction of flushing and diarrhea symptoms related to carcinoid tumors and/or vasoactive intestinal peptide (VIPoma) tumors.[L14513] The delayed-release oral formulation is used for the long-term treatment of acromegaly in patients who tolerate and respond adequately to injectable octreotide and [lanreotide].[L14507,L45528]

Octreotide mimics the naturally occurring hormone known as somatostatin. Like somatostatin, it demonstrates activity against growth hormone and glucagon, treating the disordered tissue growth and insulin regulation in patients with acromegaly.[L14501,L14513] In addition, octreotide relieves the flushing and diarrhea associated with gastrointestinal tumors by reducing splanchnic blood flow[A214727] and various gastrointestinal hormones associated with diarrhea.[A214721] Product labeling warns that octreotide may reduce gallbladder contractility, bile secretion, and the release of thyroid-stimulating hormone (TSH) in healthy volunteers.[L14513] In addition, reports of decreased vitamin B12 in patients treated with octreotide have been made. Ensure to monitor vitamin B12 levels in patients taking octreotide.[L14528]

Octreotide binds to somatostatin receptors coupled to phospholipase C through G proteins and leads to smooth muscle contraction in the blood vessels.[L14519] Downstream effects that stimulate phospholipase C, the production of 1, 4,5-inositol triphosphate, and action on the L-type calcium channels lead to the inhibition of growth hormone, treating the various growth-hormone and metabolic effects of acromegaly.[L14519] Octreotide's suppression of luteinizing hormone (LH)[A214724], reduction in splanchnic blood flow[A214727], and inhibition of serotonin, gastrin, vasoactive intestinal peptide, secretin, motilin, and pancreatic polypeptide provide relief for the gastrointestinal and flushing symptoms of carcinoid and/or VIPoma tumors.[A214721]

After a subcutaneous dose, octreotide is absorbed completely upon administration.[A214721,L14513] After the administration of an oral delayed-release capsule, peak concentrations were found to be 33% lower than after subcutaneous administration.[L14528] The Cmax was attained at 1.67–2.5 hours after oral administration versus 30 minutes for the subcutaneous route. At 20 mg twice a day in patients with acromegaly, peak concentration was 2.5 mg/nL versus 5.30 ng/mL at 40 mg twice a day.[L14528] AUC increases in proportion with the dose, regardless of the route.[A214721,L14528]

Octreotide has been reported to be heavily metabolized in the liver.[A214721]

There is limited information regarding cases of octreotide overdose aside from case reports of an overdose with injectable octreotide. The dose ranged from 2.4 mg/day to 6 mg/day administered by continuous infusion or subcutaneous administration of 1.5 mg three times daily. Effects of an overdose with octreotide may include hypotension, brain hypoxia, arrhythmia, cardiac arrest, lactic acidosis, pancreatitis, hepatomegaly, diarrhea, flushing, lethargy, and weakness.[L14528]

After a subcutaneous dose, the plasma half-life is estimated to be 0.2 hours. The average elimination half-lives for subcutaneous and oral administration ranged from 2.3 - 2.7 hours and did not differ significantly.[L14528] One pharmacokinetic study revealed a plasma half-life ranging from 72-113 minutes.[A214721]

Approximately 65% of the dose is bound in the plasma to lipoproteins and albumin.[L14513,L14528]

About 32% of an oral octreotide dose is excreted into the urine [L14528] and 30-40% is excreted by the liver into the feces.[A214721]. About 11% of the unchanged parent drug is found in the urine, and 2% of the unchanged parent drug can be recovered in the feces.[A214721]

In a pharmacokinetic study, the volume of distribution was 13.6 L in healthy volunteers.[L14528] One pharmacokinetic study revealed a volume of distribution ranging from 18.1-30.4L after intravenous administration in healthy volunteers.[A214721]

The total body clearance of octreotide is 7-10 L/h.[L14528] One pharmacokinetic study revealed a total body clearance of 11.4 L/h.[A214721]

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved", "investigational" ]

[ "H01CB", "H01C", "H01", "H" ]

[ "Humans and other mammals" ]

[ { "cost": "3.6", "description": "Octreotide acet 50 mcg/ml vial", "unit": "ml" }, { "cost": "11.92", "description": "Sandostatin 0.05 mg/ml ampul", "unit": "ml" }, { "cost": "14.4", "description": "Octreotide acet 200 mcg/ml vial", "unit": "ml" }, { "cost": "15.36", "description": "Octreotide acet 100 mcg/ml vial", "unit": "ml" }, { "cost": "23.11", "description": "Sandostatin 0.1 mg/ml ampul", "unit": "ml" }, { "cost": "24.48", "description": "Octreotide acet 500 mcg/ml vial", "unit": "ml" }, { "cost": "47.66", "description": "Sandostatin 0.2 mg/ml vial", "unit": "ml" }, { "cost": "67.2", "description": "Octreotide 1000 mcg/ml vial", "unit": "ml" }, { "cost": "111.48", "description": "Sandostatin 0.5 mg/ml ampul", "unit": "ml" }, { "cost": "234.49", "description": "Sandostatin 1 mg/ml vial", "unit": "ml" }, { "cost": "1967.81", "description": "Sandostatin lar 10 mg kit", "unit": "kit" }, { "cost": "2578.19", "description": "Sandostatin lar 20 mg kit", "unit": "kit" }, { "cost": "3860.62", "description": "Sandostatin lar 30 mg kit", "unit": "kit" } ]

[ { "approved": "1996-07-23", "country": "United States", "expires": "2013-07-23", "number": "5538739" }, { "approved": "1994-04-12", "country": "Canada", "expires": "2011-04-12", "number": "1328402" }, { "approved": "1999-07-13", "country": "United States", "expires": "2017-01-13", "number": "5922338" }, { "approved": "1999-07-13", "country": "United States", "expires": "2017-01-13", "number": "5922682" }, { "approved": "1998-05-19", "country": "United States", "expires": "2015-11-19", "number": "5753618" }, { "approved": "1998-03-17", "country": "United States", "expires": "2017-01-30", "number": "5728396" }, { "approved": "2000-12-05", "country": "United States", "expires": "2017-01-30", "number": "6156331" }, { "approved": "2002-04-23", "country": "United States", "expires": "2018-12-17", "number": "6375978" }, { "approved": "2001-05-22", "country": "United States", "expires": "2017-06-13", "number": "6235712" }, { "approved": "2000-09-05", "country": "United States", "expires": "2018-07-24", "number": "6113938" }, { "approved": "2000-09-26", "country": "United States", "expires": "2017-06-13", "number": "6124261" }, { "approved": "2002-05-28", "country": "United States", "expires": "2017-01-30", "number": "6395292" }, { "approved": "2000-10-17", "country": "United States", "expires": "2017-01-30", "number": "6132420" }, { "approved": "1999-11-16", "country": "United States", "expires": "2017-01-30", "number": "5985305" }, { "approved": "1999-08-03", "country": "United States", "expires": "2017-06-13", "number": "5932547" }, { "approved": "2019-07-09", "country": "United States", "expires": "2038-05-15", "number": "10342850" }, { "approved": "2020-06-30", "country": "United States", "expires": "2036-02-03", "number": "10695397" }, { "approved": "2013-09-17", "country": "United States", "expires": "2029-09-17", "number": "8535695" }, { "approved": "2019-03-26", "country": "United States", "expires": "2036-02-03", "number": "10238709" }, { "approved": "2017-02-14", "country": "United States", "expires": "2029-09-17", "number": "9566246" }, { "approved": "2012-12-11", "country": "United States", "expires": "2029-09-17", "number": "8329198" }, { "approved": "2016-02-23", "country": "United States", "expires": "2029-09-17", "number": "9265812" }, { "approved": "2021-07-06", "country": "United States", "expires": "2036-02-03", "number": "11052126" }, { "approved": "2021-10-12", "country": "United States", "expires": "2040-12-28", "number": "11141457" }, { "approved": "2016-02-03", "country": "United States", "expires": "2036-02-03", "number": "11338011" }, { "approved": "2016-02-03", "country": "United States", "expires": "2036-02-03", "number": "11510963" }, { "approved": "2016-02-03", "country": "United States", "expires": "2036-02-03", "number": "11857595" }, { "approved": "2020-12-28", "country": "United States", "expires": "2040-12-28", "number": "11890316" }, { "approved": "2009-09-17", "country": "United States", "expires": "2029-09-17", "number": "11969471" }, { "approved": "2009-09-17", "country": "United States", "expires": "2029-09-17", "number": "11986529" }, { "approved": "2020-11-03", "country": "United States", "expires": "2040-11-03", "number": "11246991" }, { "approved": "2020-11-03", "country": "United States", "expires": "2040-11-03", "number": "11534553" }, { "approved": "2020-11-03", "country": "United States", "expires": "2040-11-03", "number": "11052196" } ]

[ "BYNFEZIA Pen", "Mycapssa", "Mycapssa", "Mycapssa", "Ocphyl", "Ocphyl", "Ocphyl", "Octreotide", "Octreotide", "Octreotide", "Octreotide", "Octreotide", "Octreotide acetate", "Octreotide acetate", "Octreotide acetate", "Octreotide acetate", "Octreotide acetate", "Octreotide acetate", "Octreotide acetate", "Octreotide acetate", "Octreotide acetate", "Octreotide acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate", "Octreotide Acetate Injection", "Octreotide Acetate Injection", "Octreotide Acetate Injection", "Octreotide Acetate Injection - 100mcg/ml", "Octreotide Acetate Injection - 200mcg/ml", "Octreotide Acetate Injection - 500mcg/ml", "Octreotide Acetate Injection - 50mcg/ml", "Octreotide Acetate Omega", "Octreotide Acetate Omega", "Octreotide Acetate Omega", "Octreotide Acetate Omega", "Octreotide for Injectable Suspension", "Octreotide for Injectable Suspension", "Octreotide for Injectable Suspension", "Octreotide Injection", "Octreotide Injection", "Octreotide Injection", "Octreotide Injection", "Octreotide Injection", "Octreotide Injection", "Octreotide Injection", "Octreotide Injection", "Sandostatin", "Sandostatin", "Sandostatin", "Sandostatin", "Sandostatin", "Sandostatin", "Sandostatin", "Sandostatin", "Sandostatin", "Sandostatin Lar", "Sandostatin Lar", "Sandostatin Lar", "Sandostatin LAR Depot", "Sandostatin LAR Depot", "Sandostatin LAR Depot", "Sandostatin LAR Depot", "Sandostatin LAR Depot", "Sandostatin LAR Depot", "Sandostatin LAR Depot", "Sandostatin LAR Depot", "Sandostatin LAR Depot", "Sandostatin LAR Depot Demonstration kit" ]

[ "Sandostatin LAR" ]

[]

[ "P30874" ]

[ "P05164", "P08684" ]

[ "P02768" ]

[ "P08183", "Q92887" ]

DB00105

Interferon alfa-2b

Interferon alpha 2b (human leukocyte clone hif-sn 206 protein moiety reduced). A type I interferon consisting of 165 amino acid residues with arginine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent.

liquid

For the treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma.

Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R.

Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which upon dimerization activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta.

Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously.

null

There is limited experience with overdosage. Postmarketing surveillance includes reports of patients receiving a single dose as great as 10 times the recommended dose. In general, the primary effects of an overdose are consistent with the effects seen with therapeutic doses of interferon alfa-2b. Hepatic enzyme abnormalities, renal failure, hemorrhage, and myocardial infarction have been reported with single administration overdoses and/or with longer durations of treatment than prescribed. Toxic effects after ingestion of interferon alfa-2b are not expected because interferons are poorly absorbed orally.

The elimination half-life following both intramuscular and subcutaneous injections was approximately 2 to 3 hours. The elimination half-life was approximately 2 hours following intravenous injection.

null

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

[ "approved" ]

[ "L03AB", "L03A", "L03", "L" ]

[ "Humans and other mammals" ]

[ { "cost": "394.21", "description": "Intron a 3 million unit/ml pen", "unit": "pen" }, { "cost": "657.06", "description": "Intron a 5 million unit/ml pen", "unit": "pen" }, { "cost": "683.34", "description": "Intron-A 5000000 unit/0.2ml Kit Box", "unit": "box" }, { "cost": "1068.12", "description": "Intron a 10 million unit pen", "unit": "pen" }, { "cost": "1110.84", "description": "Intron-A 10000000 unit/0.2ml Kit (each Box Contains One 6 Dose 1.5ml Pen)", "unit": "box" } ]

[ { "approved": "2008-02-19", "country": "Canada", "expires": "2025-02-19", "number": "1341567" }, { "approved": "1999-06-15", "country": "Canada", "expires": "2015-10-10", "number": "2201749" } ]

[ "Intron A", "Intron A", "Intron A", "Intron A", "Intron A", "Intron A", "Intron A", "Intron A", "Intron A", "Intron A", "Intron A", "Intron A", "Intron A", "Intron A", "Intron A", "Intron A", "Intron A", "Intron A", "Intron A - Kit (pws+diluent) 3000000iu/vial", "Intron A - Kit (pws+diluent) 5000000iu/vial", "Intron A - Liq 5000000iu/ml", "Intron A Inj 10000000unit/vial", "Intron A Inj 3000000unit/vial", "Intron A Inj 5000000unit/vial", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Introna", "Rebetron Ready To Use Solution (albumin(human)free) (6000000 Iu/ml and 200mg Capsules)", "Rebetron Solution (albumin (human) Free) (18 Miu Multi-dose Pen / 200mg Capsules)" ]

[ "Locteron" ]

[ "Intron A", "Intron A - Kit (pws+diluent) 3000000iu/vial", "Intron A - Kit (pws+diluent) 5000000iu/vial", "Rebetron Ready To Use Solution (albumin(human)free) (6000000 Iu/ml and 200mg Capsules)", "Rebetron Solution (albumin (human) Free) (18 Miu Multi-dose Pen / 200mg Capsules)", "Intron A" ]

[ "P48551", "P01563", "P17181" ]

[ "P05177" ]

[]

DB00106

Abarelix

Synthetic decapeptide antagonist to gonadotropin releasing hormone (GnRH). It is marketed by Praecis Pharmaceuticals as Plenaxis. Praecis announced in June 2006 that it was voluntarily withdrawing the drug from the market.

solid

For palliative treatment of advanced prostate cancer.

Used in the palliative treatment of advanced prostate cancer. Abarelix is a luteinizing hormone agonist that results in suppression of testicular or follicular steroidogenesis.

Abarelix binds to the gonadotropin releasing hormone receptor and acts as a potent inhibitor of gonadotropin secretion.

Following IM administration of 100 mg, abarelix is absorbed slowly with a mean peak concentration of 43.4 ng/mL observed approximately 3 days after the injection.

In vitro hepatocyte (rat, monkey, human) studies and in vivo studies in rats and monkeys showed that the major metabolites of abarelix were formed via hydrolysis of peptide bonds. No significant oxidative or conjugated metabolites of abarelix were found either in vitro or in vivo. There is no evidence of cytochrome P-450 involvement in the metabolism of abarelix.

The maximum tolerated dose of abarelix has not been determined. The maximum dose used in clinical studies was 150 mg. There have been no reports of accidental overdose with abarelix.

13.2 ± 3.2 days

96-99%

null

Organic compounds

Organic acids and derivatives

Carboxylic acids and derivatives

Amino acids, peptides, and analogues

[ "approved", "investigational", "withdrawn" ]

[ "L02BX", "L02B", "L02", "L" ]

[ "Humans and other mammals" ]

[]

[ { "approved": "2002-07-23", "country": "United States", "expires": "2015-06-07", "number": "6423686" }, { "approved": "2001-01-30", "country": "United States", "expires": "2016-12-11", "number": "6180608" }, { "approved": "1999-10-19", "country": "United States", "expires": "2016-12-11", "number": "5968895" }, { "approved": "1998-12-01", "country": "United States", "expires": "2015-12-01", "number": "5843901" }, { "approved": "2004-03-02", "country": "United States", "expires": "2016-12-11", "number": "6699833" } ]

Abarelix | GnRH receptor | GnRH-R | GRHR

[]

[ "Plenaxis" ]

[]

[ "P30968" ]

[]