Identification

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Name
Warfarin
Accession Number
DB00682  (APRD00341)
Type
Small Molecule
Groups
Approved
Description

Warfarin is an anticoagulant drug normally used to prevent blood clot formation as well as migration. Although originally marketed as a pesticide (d-Con, Rodex, among others), Warfarin has since become the most frequently prescribed oral anticoagulant in North America. Warfarin has several properties that should be noted when used medicinally, including its ability to cross the placental barrier during pregnancy which can result in fetal bleeding, spontaneous abortion, preterm birth, stillbirth, and neonatal death. Additional adverse effects such as necrosis, purple toe syndrome, osteoporosis, valve and artery calcification, and drug interactions have also been documented with warfarin use. Warfarin does not actually affect blood viscosity, rather, it inhibits vitamin-k dependent synthesis of biologically active forms of various clotting factors in addition to several regulatory factors.

Structure
Thumb
Synonyms
  • 4-Hydroxy-3-(3-oxo-1-phenylbutyl)coumarin
  • Coumafene
  • Warfarin
  • Warfarina
  • Zoocoumarin
Product Ingredients
IngredientUNIICASInChI Key
Warfarin potassiumI47IU4FOCO2610-86-8WSHYKIAQCMIPTB-UHFFFAOYSA-M
Warfarin sodium6153CWM0CL129-06-6KYITYFHKDODNCQ-UHFFFAOYSA-M
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CoumadinTablet2.5 mg/1OralMed Pharma Co., Ltd.2011-05-302012-07-01Us
CoumadinTablet3 mg/1OralRemedy Repack2012-07-192013-11-30Us
CoumadinTablet2.5 mg/1OralBristol-Myers Squibb Pharma Company2009-01-01Not applicableUs00056 0176 70 nlmimage10 99134caa
CoumadinTablet4 mg/1OralAphena Pharma Solutions Tennessee, Inc.2009-01-01Not applicableUs
CoumadinTablet10 mg/1OralPhysicians Total Care, Inc.2005-06-102010-06-30Us
CoumadinTablet5 mg/1OralCardinal Health2009-01-01Not applicableUs55154 770420180913 8702 wb4sqe
CoumadinTablet3 mg/1OralPhysicians Total Care, Inc.2005-11-102010-06-30Us54868 406320180907 15195 n9qhgl
CoumadinTablet1 mg/1OralCardinal Health2009-01-01Not applicableUs55154 770120180913 8702 129qdto
CoumadinTablet7.5 mg/1OralAphena Pharma Solutions Tennessee, Inc.2009-01-01Not applicableUs
CoumadinTablet10 mg/1OralRemedy Repack2012-12-122017-01-25Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-warfarinTabletOralApotex Corporation2000-10-16Not applicableCanada
Apo-warfarinTabletOralApotex Corporation2002-04-23Not applicableCanada
Apo-warfarinTabletOralApotex Corporation2000-10-16Not applicableCanada
Apo-warfarinTabletOralApotex Corporation2000-10-16Not applicableCanada
Apo-warfarinTabletOralApotex Corporation2000-10-16Not applicableCanada
Apo-warfarinTabletOralApotex Corporation2000-10-16Not applicableCanada
Apo-warfarinTabletOralApotex Corporation2000-10-16Not applicableCanada
JantovenTablet7.5 mg/1OralUpsher-Smith Laboratories, LLC2010-02-23Not applicableUs
JantovenTablet2.5 mg/1OralUpsher-Smith Laboratories, LLC2010-02-23Not applicableUs
JantovenTablet4 mg/1OralRemedy Repack2013-05-242014-02-07Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Lawarin / Marevan / Waran / Warfant
Categories
UNII
5Q7ZVV76EI
CAS number
81-81-2
Weight
Average: 308.3279
Monoisotopic: 308.104859
Chemical Formula
C19H16O4
InChI Key
PJVWKTKQMONHTI-UHFFFAOYSA-N
InChI
InChI=1S/C19H16O4/c1-12(20)11-15(13-7-3-2-4-8-13)17-18(21)14-9-5-6-10-16(14)23-19(17)22/h2-10,15,21H,11H2,1H3
IUPAC Name
4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-chromen-2-one
SMILES
CC(=O)CC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2

Pharmacology

Indication

Indicated for:Label,17

1) Prophylaxis and treatment of venous thromboembolism and related pulmonary embolism.

2) Prophylaxis and treatment of thromboembolism associated with atrial fibrillation.

3) Prophylaxis and treatment of thromboembolism associated with cardiac valve replacement.

4) Use as adjunct therapy to reduce mortality, recurrent myocardial infarction, and thromboembolic events post myocardial infarction.

Off-label uses include:

1) Secondary prevention of stroke and transient ischemic attacks in patients with rheumatic mitral valve disease but without atrial fibrillation.10

Associated Conditions
Pharmacodynamics

Warfarin is an anticoagulant, as such it disrupts the coagulation cascade to reduce frequency and extent of thrombus formation.Label,17 In patients with deep vein thrombosis or atrial fibrillation there is an increased risk of thrombus formation due to the reduced movement of blood.15 For patients with cardiac valve disease or valve replacements this increased coagulability is due to tissue damage. Thrombi due to venous thrombosis can travel to the lungs and become pulmonary emboli, blocking circulation to a portion of lung tissue. Thrombi which form in the heart can travel to the brain and cause ischemic strokes. Prevention of these events is the primary goal of warfarin therapy.

Limitation of thrombus formation is also a source of adverse effects. In patients with atheroscelotic plaques rupture typically results in thrombus formation.11 When these patients are anticoagulated plaque rupture can allow the escape of cholesterol from the lipid core in the form of atheroemboli or cholesterol microemboli. These emboli are smaller than thrombi and block smaller vessels, usually less than 200 μm in diameter. The consequences of this are varied and depend on the location of the blockage. Effects include visual disturbances, acute kidney injury or worsening of chronic kidney disease, central nervous system ischemia, and purple or blue toe syndrome.Label,11 Blue toe syndrome can be reversed if it has not progressed to tissue necrosis but the other effects of microemboli are often permanent.

Antocoagulation appears to mediate warfarin-related nephropathy, a seemingly spontaneous kidney injury or worsening of chronic kidney disease associated with warfarin therapy.12 Nephropathy in this case appears to be due to increased passage of red blood cells through the glomerulus and subsequent blockage of renal tubules with red blood cell casts. This is worsened or possibly triggered by pre-existing kidney damage. Increased risk of warfarin-related nephropathy occurs at INRs over 3.0 but risk does not increase as a function of INR beyond this point.

Warfarin has been linked to the development of calciphylaxis.Label This is thought to be due to warfarin's inhibition of vitamin K(VKA) recycling as VKA is needed for the carboxylation of matrix Gla protein.13 This protein is an anti-calcification factor and its inhibition through preventing the carboxylation step in its production leads to a shift in calcification balance in favor of calciphylaxis.

Tissue necrosis can occur early on in warfarin therapy.Label This is attributable to half lives of the clotting factors impacted by inhibition of vitamin K recycling.Label,14 Proteins C and S are anticoagulation factors with half lives of 8 and 24 hours respectively. The coagulation factors IX, X, VII, and thrombin (factor II) have half lives of 24, 36, 6, and 50 hours respectively. This means proteins C and S are inactivated sooner than pro-coagulation proteins, with the exception of factor VII, resulting in a pro-thrombotic state for the first few days of therapy. Thrombi which form in this time period can occlude arterioles in various locations, blocking blood flow and causing tissue necrosis due to ischemia.

Mechanism of action

Warfarin is a vitamin K antagonist which acts to inhibit the production of vitamin K by vitamin K epoxide reductase.Label,14,16 The reduced form of vitamin K, vitamin KH2 is a cofactor used in the γ-carboxylation of coagulation factors VII, IX, X, and thrombin. Carboxylation induces a conformational change allowing the factors to bind Ca2+ and to phospholipid surfaces. Uncarboxylated factors VII, IX, X, and thrombin are biologically inactive and therefore serve to interrupt the coagulation cascade. The endogenous anticoagulation proteins C and S also require γ-carboxylation to function. This is particularly true in the case of thrombin which must be activated in order to form a thrombus. vitamin KH2 is converted to vitamin K epoxide as part of the γ-carboxylation reaction catalyzed by γ-glutamyl carboxylase. Vitamin K epoxide is then converted to vitamin K1 by vitamin K epoxide reductase then back to vitamin KH2 by vitamin K reductase. Warfarin binds to vitamin K epoxide reductase complex subunit 1 and irreversibly inhibits the enzyme thereby stopping the recycling of vitamin K by preventing the conversion of vitamin K epoxide to vitamin K1. This process creates a hypercoagulable state for a short time as proteins C and S degrade first with half lives of 8 and 24 hours, with the exception of factor VII which has a half life of 6 hours.14 Factors IX, X, and finally thrombin degrade later with half lives of 24, 36, and 50 hours resulting in a dominant anticoagulation effect.14 In order to reverse this anticoagulation vitamin K must be supplied, either exogenously or by removal of the vitamin K epoxide reductase inhibition, and time allowed for new coagulation factors to be synthesized.Label,14,16 It takes approximately 2 days for new coagulation factors to be synthesized in the liver. Vitamin K2, functionally identical to vitamin K1, is synthesized by gut bacteria leading to interactions with antibiotics as elimination of these bacteria can reduce vitamin K216

TargetActionsOrganism
AVitamin K epoxide reductase complex subunit 1
inhibitor
Humans
UNuclear receptor subfamily 1 group I member 2Not AvailableHumans
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Completely absorbed from the GI tract. The mean Tmax for warfarin sodium tablets is 4 hours.Label,17,9

Volume of distribution

Vd of 0.14 L/kg.Label,17,9 Warfarin has a distrubution phase lasting 6-12 hours.17 It is known to cross the placenta and achieves fetal serum concentrations similar to maternal concentrations.

Protein binding

99% bound primarily to albumin.Label,17,9

Metabolism

Metabolism of warfarin is both stereo- and regio-selective.9 The major metabolic pathway is oxidation to various hydroxywarfarins, comprising 80-85% of the total metabolites. CYP2C9 is the major enzyme catalyzing the 6- and 7-hydroxylation of S-warfarin while 4'-hydroxylation occurs through CYP2C18 with minor contributions from CYP2C19. R-warfarin is metabolized to 4'-hydroxywarfarin by CYP2C8 with some contirbuting by CYP2C19, 6- and 8-hydroxywarfarin by CYP1A2 and CYP2C19, 7-hydroxywarfarin by CYP1A2 and CYP2C8, and lastly to 10-hydroxywarfarin by CYP3A4. The 10-hydroxywarfarin metabolite as well as a benzylic alcohol metabolite undergo an elimination step to form dehydrowarfarin. The minor pathway of metabolism is the reduction of the ketone group to warfarin alcohols, comprising 20% of the metabolites. Limited conjugation occurs with sulfate and gluronic acid groups but these metabolites have only been confirmed for R-hydroxywarfarins.

Route of elimination

The elimination of warfarin is almost entirely by metabolism with a small amount excreted unchanged.Label,17,9 80% of the total dose is excreted in the urine with the remaining 20% appearing in the feces.9

Half life

R-warfarin is cleared more slowly than S-warfarin, at about half the rate.Label T1/2 for R-warfarin is 37-89 hours. T1/2 for S-warfarin is 21-43 hours.

Clearance

Clearance of warfarin varies depending on CYP2C9 genotype.Label,17 The *2 and *3 alleles appear in the Caucasian population at frequencies of 11% and 7% and are known to reduce clearance warfarin. Additional clearance reducing genotypes include the *5, *6, *9 and *11 alleles. Genotypes for which population clearance estimates have been found are listed below.

*1/*1 = 0.065 mL/min/kg

*1/*2, *1/*3 = 0.041 mL/min/kg

*2/*2, *2/*3, *3/*3 = 0.020 mg/min/kg

Toxicity

LD50 Values

Mouse: 3 mg/kg (Oral), 165 mg/kg (IV), 750 mg/kg (IP)18

Rat: 1.6 mg/kg (Oral), 320 mg/kg (Inhaled), 1400 mg/kg (Skin)18

Rabbit: 800 mg/kg (Oral)18

Pig: 1 mg/kg (Oral)18

Dog: 3 mg/kg (Oral)18

Cat: 6 mg/kg (Oral)18

Chicken: 942 mg/kg (Oral)18

Guinea Pig: 180 mg/kg (Oral)18

Overdose

Doses of 1-2 mg/kg/day over a period of 15 days have been fatal in humans.19 Warfarin overdose is primarily associated with major bleeding particularly from the mucous membranes, gastrointestinal tract, and genitourinary system.Label,19 Epistaxis, ecchymoses, as well as renal and hepatic bleeding are also associated. These symptoms become apparent within 2-4 days of overdose although increases in prothrombin time can be observed within 24 hours. Treatment for overdosed patients includes discontinuation of warfarin and administration of vitamin K. For more urgent reversal of anticoagulation prothrombin complex concentrate, blood plasma, or coagulation factor VIIa infusion can be used.Label Patients can be safely re-anticoagulated after reversal of the overdose.

Carcinogenicity & Mutagenicity

The carcinogenicity and mutagenicity of warfarin have not been thoroughly investigated.Label

Reproductive Toxicity

Warfarin is known to be a teratogen and its use during pregnancy is contraindicated in the absence of high thrombotic risk.Label,19 Fetal warfarin syndrome, attributed to exposure during the 1st trimester, is characterized by nasal hypoplasia with or without stippled epiphyses, possible failure of nasal septum development, and low birth weight. Either dorsal midline dysplasia or ventral midline dysplasia can occur. Dorsal midline dysplasia includes agenisis of the corpus callosum, Dandy-Walker malformations, midline cerebellar hypoplasia. Ventral midline dysplasia is characterized by eye anomalies which can potentially include optic atrophy, blindness, and microphthalmia. Exposure during the 2nd and 3rd trimester is associated with hypoplasia of the extremities, developmental retardation, microcephaly, hydrocephaly, schizencephaly, seizures, scoliosis, deafness, congenital heart malformations, and fetal death. The critical exposure period is estimated to be week 6-9 based on case reports. Effects noted in the Canadian product monograph include developing a single kidney, asplenia, anencephaly, spina bifida, cranial nerve palsy, polydactyl malformations, corneal leukoma, diaphragm hernia, and cleft palate.17

Lactation

Official product monographs mention a study in 15 women.Label,17 Warfarin was not detected in the breast milk of any woman and 6 infants were documented as having normal prothrombin times. The remaining 9 infants were not tested. Another study in 13 women using doses of 2-12 mg also revealed no detectable warfarin in breast milk.20 A woman who mistakenly took 25 mg of warfarin for 7 days while breastfeeding presented to an emergency room with an INR of 10 and prothrombin time of over 100 s. Her infant had a normal INR of 1.0 and prothrombin time of 10.3. The infant in this case has an increased prothrombin time of 33.8 s three weeks previous but this was judged not to be due to warfarin exposure.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Warfarin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2C9CYP2C9*2(T;T) / (C;T)T AlleleEffect Directly StudiedPatients with this genotype have reduced metabolism of warfarin.Details
Vitamin K epoxide reductase complex subunit 1---(A;A) / (A;G)-1639G>AEffect Directly StudiedPatients with this genotype in VKORC1 are associated with reduced metabolism of warfarin and increased risk of serious bleeding thus require lower doses.Details
Phylloquinone omega-hydroxylase CYP4F2---(T;T)T Allele, homozygousEffect Directly StudiedPatients with this genotype in CP4F2 may require higer doses of warfarin to attain therapeutic anticoagulant activity.Details
Cytochrome P450 2C9CYP2C9*2(T;T) / (C;T)T AlleleEffect Directly StudiedThe presence of this polymorphism in CYP2C9 is associated with reduction in warfarin metabolism.Details
Cytochrome P450 2C9CYP2C9*3(C;C) / (A;C)C AlleleEffect Directly StudiedThe presence of this polymorphism in CYP2C9 is associated with reduction in warfarin metabolism.Details
Cytochrome P450 2C9CYP2C9*4Not Available1076T>CEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*5Not Available1080C>GEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*8Not Available449G>AEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*11Not Available1003C>TEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*12Not Available1465C>TEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*13Not Available269T>CEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*14Not Available374G>AEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*16Not Available895A>GEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*18Not Available1075A>C / 1190A>C  … show all Effect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*26Not Available389C>GEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*28Not Available641A>TEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*30Not Available1429G>AEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*33Not Available395G>AEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*6Not Available818delAEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*15Not Available485C>AEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*25Not Available353_362delAGAAATGGAAEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*35Not Available374G>T / 430C>TEffect InferredPoor drug metabolizer, lower dose recommended.Details
Cytochrome P450 2C9CYP2C9*6Not Available818delAEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*15Not Available485C>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*25Not Available353_362delAGAAATGGAAEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*35Not Available374G>T / 430C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*3Not Available1075A>CEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*4Not Available1076T>CEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*5Not Available1080C>GEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*8Not Available449G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*11Not Available1003C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*12Not Available1465C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*13Not Available269T>CEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*14Not Available374G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*16Not Available895A>GEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*18Not Available1075A>C / 1190A>C  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*26Not Available389C>GEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*28Not Available641A>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*30Not Available1429G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*33Not Available395G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(1,2,6,7-3H)Testosterone(1,2,6,7-3H)Testosterone may increase the anticoagulant activities of Warfarin.
(R)-warfarinThe metabolism of Warfarin can be increased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Warfarin can be increased when combined with (S)-Warfarin.
1-Testosterone1-Testosterone may increase the anticoagulant activities of Warfarin.
18-methyl-19-nortestosterone18-methyl-19-nortestosterone may increase the anticoagulant activities of Warfarin.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Warfarin.
25-desacetylrifapentineThe risk or severity of bleeding can be increased when 25-desacetylrifapentine is combined with Warfarin.
3,5-diiodothyropropionic acidThe metabolism of Warfarin can be decreased when combined with 3,5-diiodothyropropionic acid.
3,5-Diiodotyrosine3,5-Diiodotyrosine may increase the anticoagulant activities of Warfarin.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Warfarin.
Additional Data Available
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    Severity

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Food Interactions
  • Avoid alcohol.
  • Avoid drastic changes in dietary habit.
  • Avoid St. John's Wort.
  • Consult your doctor before ingesting large amounts of dietary Vitamin K (e.g. from green leafy vegetables).
  • Limit garlic, ginger, gingko, and horse chestnut.

References

Synthesis Reference

Nasri W. Badran, "Microcrystalline 3-(alpha-acetonylbenzyl)-4-hydroxycoumarin (warfarin) and methods of making." U.S. Patent US4113744, issued April, 1960.

US4113744
General References
  1. Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E: The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):204S-233S. [PubMed:15383473]
  2. Whitlon DS, Sadowski JA, Suttie JW: Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry. 1978 Apr 18;17(8):1371-7. [PubMed:646989]
  3. Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW: Identification of the gene for vitamin K epoxide reductase. Nature. 2004 Feb 5;427(6974):541-4. [PubMed:14765195]
  4. Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Muller CR, Strom TM, Oldenburg J: Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004 Feb 5;427(6974):537-41. [PubMed:14765194]
  5. Hirsh J, Fuster V, Ansell J, Halperin JL: American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol. 2003 May 7;41(9):1633-52. [PubMed:12742309]
  6. Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, Wells PS: Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005 May 23;165(10):1095-106. [PubMed:15911722]
  7. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G: Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):160S-198S. doi: 10.1378/chest.08-0670. [PubMed:18574265]
  8. Freedman MD: Oral anticoagulants: pharmacodynamics, clinical indications and adverse effects. J Clin Pharmacol. 1992 Mar;32(3):196-209. [PubMed:1564123]
  9. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [PubMed:16372822]
  10. Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, Fang MC, Fisher M, Furie KL, Heck DV, Johnston SC, Kasner SE, Kittner SJ, Mitchell PH, Rich MW, Richardson D, Schwamm LH, Wilson JA: Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014 Jul;45(7):2160-236. doi: 10.1161/STR.0000000000000024. Epub 2014 May 1. [PubMed:24788967]
  11. Saric M, Kronzon I: Aortic atherosclerosis and embolic events. Curr Cardiol Rep. 2012 Jun;14(3):342-9. doi: 10.1007/s11886-012-0261-2. [PubMed:22437371]
  12. Brodsky SV: Anticoagulants and acute kidney injury: clinical and pathology considerations. Kidney Res Clin Pract. 2014 Dec;33(4):174-80. doi: 10.1016/j.krcp.2014.11.001. Epub 2014 Nov 18. [PubMed:26885473]
  13. Portales-Castillo I, Kroshinsky D, Malhotra CK, Culber-Costley R, Cozzolino MG, Karparis S, Halasz CL, Goverman J, Manley HJ, Malhotra R, Nigwekar SU: Calciphylaxis-as a drug induced adverse event. Expert Opin Drug Saf. 2019 Jan;18(1):29-35. doi: 10.1080/14740338.2019.1559813. Epub 2018 Dec 24. [PubMed:30574812]
  14. Fawzy AM, Lip GYH: Pharmacokinetics and pharmacodynamics of oral anticoagulants used in atrial fibrillation. Expert Opin Drug Metab Toxicol. 2019 May;15(5):381-398. doi: 10.1080/17425255.2019.1604686. Epub 2019 Apr 19. [PubMed:30951640]
  15. Aster JC, Bunn HF (2017). Pathophysiology of Blood Disorders (2nd ed.). McGraw-Hill.
  16. Brunton LL, Hilal-Dandan R, Knollmann BC. eds (2018). Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education. [ISBN:978-1-25-958473-2]
  17. Warfarin DPD Monograph [Link]
  18. ChemIDplus: Warfarin [Link]
  19. HSDB: Warfarin [Link]
  20. LactMed: Warfarin [Link]
External Links
Human Metabolome Database
HMDB0001935
KEGG Compound
C01541
PubChem Compound
54678486
PubChem Substance
46504711
ChemSpider
10442445
BindingDB
50343352
ChEBI
87732
ChEMBL
CHEMBL1464
Therapeutic Targets Database
DAP000770
PharmGKB
PA451906
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Warfarin
ATC Codes
B01AA03 — Warfarin
AHFS Codes
  • 20:12.04.08 — Coumarin Derivatives
FDA label
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MSDS
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentMalignant Neoplasm of Pancreas1
1Active Not RecruitingBasic ScienceNeoplasms Metastasis1
1Active Not RecruitingOtherCardiovascular Disease (CVD) / Elevated Lipoprotein(a)1
1Active Not RecruitingOtherNeoplasms1
1Active Not RecruitingTreatmentKnee Osteoarthritis (Knee OA)1
1CompletedNot AvailableHealthy Volunteers4
1CompletedNot AvailableHealthy Volunteers / Pharmacodynamics of Warfarin / Pharmacokinetics of Isavuconazole / Pharmacokinetics of S- and R-warfarin1
1CompletedNot AvailableHypertension,Essential1
1CompletedNot AvailableMalignant Lymphomas / Tumors, Solid1
1CompletedNot AvailableThrombosis, Venous1
1CompletedBasic ScienceAlzheimer's Disease (AD)1
1CompletedBasic ScienceAnticoagulant Effect of Warfarin When Taken With Duloxetine1
1CompletedBasic ScienceAtopic Dermatitis (AD)1
1CompletedBasic ScienceDrug Drug Interaction (DDI) / Healthy Volunteers1
1CompletedBasic ScienceDrug Interaction Potentiation1
1CompletedBasic ScienceHealthy Volunteers5
1CompletedBasic ScienceHealthy Volunteers / Pharmacokinetics of FG-45921
1CompletedBasic ScienceHealthy Volunteers / Rheumatoid Arthritis1
1CompletedBasic ScienceHealthy Volunteers / Type 2 Diabetes Mellitus1
1CompletedBasic SciencePharmacokinetics / Urinary Bladder, Overactive1
1CompletedBasic SciencePharmakokinetic1
1CompletedBasic SciencePsoriasis1
1CompletedBasic ScienceRheumatoid Arthritis1
1CompletedOtherALK-positive Advanced Tumors1
1CompletedOtherHealthy Volunteers2
1CompletedPreventionChemotherapy-Induced Nausea and Vomiting (CINV) / Healthy Volunteers1
1CompletedScreeningHealthy Volunteers1
1CompletedTreatmentAlzheimer's Disease (AD)1
1CompletedTreatmentAlzheimer's Disease (AD) / Huntington's Disease (HD)1
1CompletedTreatmentAnticoagulation1
1CompletedTreatmentCastration Resistant Prostate Cancer (CRPC) / Pharmacokinetics of MDV31001
1CompletedTreatmentDiabetes Mellitus (DM) / Healthy Volunteers1
1CompletedTreatmentDiabetes Mellitus (DM) / Healthy Volunteers / Type 2 Diabetes Mellitus1
1CompletedTreatmentEpilepsies1
1CompletedTreatmentHaematological Malignancies / Tumors, Solid1
1CompletedTreatmentHealthy Volunteers17
1CompletedTreatmentHealthy Volunteers / Hemostasis1
1CompletedTreatmentHeathy Volunteer1
1CompletedTreatmentHypertriglyceridemias1
1CompletedTreatmentMajor Depressive Disorder (MDD)1
1CompletedTreatmentMalignancies1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentParkinson's Disease (PD)2
1CompletedTreatmentPsoriasis2
1CompletedTreatmentSystemic Embolism / Thrombophlebitis1
1CompletedTreatmentType 2 Diabetes Mellitus4
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentUrinary Bladder, Overactive1
1RecruitingOtherCrohn's Disease (CD)1
1RecruitingTreatmentAtopic Dermatitis (AD)1
1RecruitingTreatmentCytochrome P450 Interaction1
1Unknown StatusTreatmentStrokes1
1WithdrawnBasic SciencePharmacodynamics / Pharmacokinetics1
1WithdrawnTreatmentHealthy Volunteers1
1WithdrawnTreatmentStroke, Ischemic1
1, 2RecruitingTreatmentCerebral Venous Thrombosis1
1, 2RecruitingTreatmentVenous Thromboembolism (VTE)1
1, 2TerminatedTreatmentMultiple Myeloma (MM) / Plasma Cell Neoplasms1
2Active Not RecruitingTreatmentValvular Heart Disease1
2CompletedPreventionArthroplasty, Replacement, Knee1
2CompletedPreventionDeep Vein Thrombosis (DVT) / Nonvalvular Atrial Fibrillation / Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)1
2CompletedPreventionNonvalvular Atrial Fibrillation8
2CompletedPreventionNonvalvular Atrial Fibrillation / Strokes1
2CompletedPreventionNonvalvular Atrial Fibrillation / Thromboembolism1
2CompletedPreventionPersistent or Permanent Nonvalvular Atrial Fibrillation1
2CompletedTreatmentDeep Vein Thrombosis (DVT) / Thrombosis, Venous1
2CompletedTreatmentEmbolism and Thrombosis1
2CompletedTreatmentFibrosis, Liver1
2CompletedTreatmentHeart Valve Diseases / Nonvalvular Atrial Fibrillation / Thrombosis, Venous1
2CompletedTreatmentMyocardial Infarction / Nonvalvular Atrial Fibrillation / Stroke, Ischemic / Venous Thromboembolism (VTE)1
2CompletedTreatmentNonvalvular Atrial Fibrillation3
2CompletedTreatmentProstate Cancer / Thromboembolism1
2CompletedTreatmentStroke, Ischemic / Transient Ischaemic Attack (TIA)1
2Not Yet RecruitingTreatmentAnticoagulant-induced Bleeding1
2Not Yet RecruitingTreatmentEnd Stage Renal Failure on Dialysis / Nonvalvular Atrial Fibrillation1
2RecruitingPreventionMyocardial Infarction1
2RecruitingTreatmentCerebral Venous Thrombosis1
2RecruitingTreatmentResidual Pulmonary Hypertension1
2RecruitingTreatmentThrombotic events1
2TerminatedPreventionHeart Valve Diseases1
2TerminatedPreventionHeart Valve Prosthesis / Thromboembolism1
2TerminatedTreatmentBleeding / Thrombotic events1
2TerminatedTreatmentPulmonary Hypertension (PH)1
2TerminatedTreatmentCardiac surgery, heparin-induced thrombocytopenia and thrombosis syndrome1
2WithdrawnNot AvailableNonvalvular Atrial Fibrillation1
2, 3Active Not RecruitingPreventionCoronary Artery Bypass Graft Surgery Patients / Deep Venous Thrombosis / Postoperative Atrial Fibrilation / Strokes / Systemic Embolism1
2, 3CompletedPreventionNonvalvular Atrial Fibrillation / Strokes1
2, 3CompletedPreventionPulmonary Embolism (PE) / Thrombosis, Venous1
2, 3Not Yet RecruitingTreatmentAntiphospholipid Syndrome1
2, 3RecruitingTreatmentAnticoagulants and Bleeding Disorders / Prostheses and Implants / Strokes / Valve Heart Disease1
2, 3TerminatedTreatmentPrimary Disease1
2, 3Unknown StatusTreatmentAtrial Flutter / Myocardial Infarction / Nonvalvular Atrial Fibrillation / Prophylaxis of cardiomyopathy / Venous Thromboembolic Diseases1
3CompletedNot AvailableCardiovascular Disease (CVD) / Thrombosis, Venous / Venous Thromboembolism (VTE)1
3CompletedPreventionAnticoagulation in Pregnancy1
3CompletedPreventionArrythmias / Cardiovascular Disease (CVD) / Cerebral Embolism and Thrombosis / Cerebrovascular Accidents / Cerebrovascular Diseases / Heart Diseases / Nonvalvular Atrial Fibrillation / Thrombophlebitis1
3CompletedPreventionAtrial Flutter / Nonvalvular Atrial Fibrillation1
3CompletedPreventionBleeding / End Stage Renal Disease (ESRD) / Thrombotic events1
3CompletedPreventionBrain Infarction / Systemic Embolism / Transient Ischaemic Attack (TIA)1
3CompletedPreventionCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Heart Diseases / Myocardial Ischemia1
3CompletedPreventionCardiovascular Disease (CVD) / Heart Diseases / Peripheral Vascular Disease (PVD) / Thromboembolism / Vascular Diseases / Venous Thromboembolism (VTE)1
3CompletedPreventionDeep Vein Thrombosis (DVT)1
3CompletedPreventionHeart Diseases / Ischaemic Heart Diseases / Myocardial Infarction / Strokes1
3CompletedPreventionNonvalvular Atrial Fibrillation1
3CompletedPreventionNonvalvular Atrial Fibrillation / Strokes1
3CompletedPreventionNonvalvular Atrial Fibrillation / Strokes / Systemic Embolism2
3CompletedPreventionNonvalvular Atrial Fibrillation / Strokes / Transient Ischaemic Attack (TIA)1
3CompletedPreventionStrokes1
3CompletedPreventionThromboembolism1
3CompletedTreatmentArterial Occlusive Diseases / Cardiovascular Disease (CVD) / Diabetes Mellitus (DM) / Heart Diseases / Vascular Diseases1
3CompletedTreatmentBleeding / Coagulation / Thrombotic events1
3CompletedTreatmentCarotid Artery Dissection / Cervical Artery Dissection / Strokes / Vertebral Artery Dissection1
3CompletedTreatmentDeep Vein Thrombosis (DVT)1
3CompletedTreatmentDeep Vein Thrombosis (DVT) / Pulmonary Embolism (PE)1
3CompletedTreatmentDeep Vein Thrombosis (DVT) / Pulmonary Embolism (PE) / Thromboembolism / Thrombosis, Venous / Venous Thromboembolism (VTE)1
3CompletedTreatmentDeep Vein Thrombosis of Lower Limb / Deep Venous Thrombosis of the Lower Extremities / Lower Extremity Deep Venous Thrombosis Recurrent / Symptomatic, recurrent Venous Thromboembolism1
3CompletedTreatmentHeart Failure1
3CompletedTreatmentIdiopathic Deep Vein Thrombosis / Recurrent Venous Thromboembolism1
3CompletedTreatmentNonvalvular Atrial Fibrillation3
3CompletedTreatmentNonvalvular Atrial Fibrillation / Percutaneous Coronary Intervention1
3CompletedTreatmentNonvalvular Atrial Fibrillation / Strokes1
3CompletedTreatmentProstate Cancer1
3CompletedTreatmentPulmonary Embolism (PE)3
3CompletedTreatmentSystemic Embolism / Thrombotic events1
3CompletedTreatmentThromboembolism4
3CompletedTreatmentThrombosis, Venous1
3CompletedTreatmentVenous Thromboembolism (VTE)1
3Enrolling by InvitationTreatmentMV(Mitral Valve) Repair1
3Not Yet RecruitingTreatmentAcute Myocardial Infarction (AMI) / Anticoagulants and Bleeding Disorders / Left Ventricular Thrombosis1
3Not Yet RecruitingTreatmentBleeding Post-mechanical Valve Replacement / Thromboembolism Post-mechanical Valve Replacement1
3Not Yet RecruitingTreatmentIliac Vein Compression Syndrome1
3Not Yet RecruitingTreatmentNonvalvular Atrial Fibrillation1
3Not Yet RecruitingTreatmentThromboembolism / Thrombotic events1
3Not Yet RecruitingTreatmentVenous Thromboembolism (VTE)1
3RecruitingOtherNonvalvular Atrial Fibrillation1
3RecruitingPreventionAnticoagulant Drugs / Cardiac Diseases1
3RecruitingPreventionAtrial Flutter / Intracranial Hemorrhage, Hypertensive / Intracranial Hemorrhages / Intraventricular Hemorrhage / Microhaemorrhage / Nonvalvular Atrial Fibrillation / Small Vessel Cerebrovascular Disease / Subarachnoid Hemorrhage / Subdural haematoma1
3RecruitingPreventionBleeding / Nonvalvular Atrial Fibrillation / Strokes1
3RecruitingPreventionCardioembolic Stroke / Nonvalvular Atrial Fibrillation1
3RecruitingPreventionRheumatic Heart Disease1
3RecruitingTreatmentAnticoagulant Adverse Reaction / Mitral Valve Stenosis / Nonvalvular Atrial Fibrillation / Rheumatic Heart Disease1
3RecruitingTreatmentCerebral Venous Thrombosis1
3RecruitingTreatmentDeep Vein Thrombosis (DVT) / Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)1
3RecruitingTreatmentIndications for Warfarin Therapy1
3RecruitingTreatmentLeft Ventricular Thrombosis1
3RecruitingTreatmentLiver Cirrhosis / Oesophageal varices haemorrhage / Portal Vein Thrombosis / Portal Vein, Cavernous Transformation Of1
3RecruitingTreatmentCardiac surgery, heparin-induced thrombocytopenia and thrombosis syndrome1
3TerminatedPreventionAtherosclerosis / Cerebral Infarctions / Constriction, Pathologic / Strokes1
3TerminatedPreventionNonvalvular Atrial Fibrillation1
3TerminatedTreatmentCardiac Dysrhythmia / Hemorrhage / Thromboembolism1
3TerminatedTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
3TerminatedTreatmentNeoplasms / Venous Thromboembolism (VTE)1
3Unknown StatusNot AvailableDeep Venous Thrombosis1
3Unknown StatusPreventionCardiovascular Disease (CVD) / Peripheral Vascular Disease (PVD)1
4Active Not RecruitingOtherDisorders, Blood Coagulation1
4Active Not RecruitingPreventionAntiphospholipid Syndrome / Thrombotic events1
4Active Not RecruitingPreventionNonvalvular Atrial Fibrillation1
4Active Not RecruitingTreatmentAnticoagulation / Nonvalvular Atrial Fibrillation1
4Active Not RecruitingTreatmentEnd Stage Renal Disease (ESRD) / Nonvalvular Atrial Fibrillation1
4Active Not RecruitingTreatmentHeart Failure1
4CompletedNot AvailableDrug Therapy, Combination1
4CompletedNot AvailableHealthy Volunteers1
4CompletedPreventionAtherosclerosis1
4CompletedPreventionHeart Defects / Triscupid Atresia1
4CompletedPreventionNonvalvular Atrial Fibrillation1
4CompletedPreventionPatent Foramen Ovale (PFO) / Stroke, Ischemic1
4CompletedTreatmentAcute Gastrointestinal Bleeding1
4CompletedTreatmentBleeding / Nonvalvular Atrial Fibrillation / Strokes / Thrombo-embolism1
4CompletedTreatmentBleeding / Thromboembolism1
4CompletedTreatmentBlood Clotting1
4CompletedTreatmentCervical Artery Dissection1
4CompletedTreatmentDeep Vein Thrombosis (DVT)3
4CompletedTreatmentDeep Vein Thrombosis (DVT) / Deep Vein Thrombosis With Pulmonary Embolism / Pulmonary Embolism (PE)1
4CompletedTreatmentDeep Vein Thrombosis (DVT) / Deep Venous Thrombosis / Nonvalvular Atrial Fibrillation / Thromboembolism / Thrombus Due to Heart Valve Prosthesis1
4CompletedTreatmentDisorders, Blood Coagulation1
4CompletedTreatmentHemorrhage / Systemic Embolism / Thrombotic events1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Liver Cirrhosis / Status;Splenectomy / Thrombosis, Venous1
4CompletedTreatmentNonvalvular Atrial Fibrillation5
4CompletedTreatmentOligohydramnios1
4Enrolling by InvitationTreatmentNonvalvular Atrial Fibrillation1
4Not Yet RecruitingPreventionAtrial Fibrillation and Flutter / End-Stage Renal Disease (ESRD) / Major Bleeding / Strokes1
4Not Yet RecruitingPreventionMitral Valve Stenosis / Nonvalvular Atrial Fibrillation1
4Not Yet RecruitingSupportive CareNonvalvular Atrial Fibrillation1
4Not Yet RecruitingTreatmentLeft Atrial Appendage Closure / Non-valvular Atrial Fibrillation (NVAF)1
4Not Yet RecruitingTreatmentLiver Cirrhosis / Portal Vein Thrombosis1
4Not Yet RecruitingTreatmentParoxysmal Nocturnal Haemoglobinuria (PNH)1
4RecruitingOtherCerebral Ischemic Events / Cognition Disorders / Dementias1
4RecruitingPreventionAntiphospholipid Syndrome / Recurrent Miscarriages1
4RecruitingPreventionHigh Blood Pressure (Hypertension) / Liver Cirrhosis / Status;Splenectomy / Thrombosis, Venous1
4RecruitingPreventionNonvalvular Atrial Fibrillation1
4RecruitingPreventionNonvalvular Atrial Fibrillation / Strokes1
4RecruitingSupportive CarePulmonary Embolism (PE) / Thrombosis, Venous1
4RecruitingTreatmentAcute Heart Failure (AHF)1
4RecruitingTreatmentAngiographically Confirmed Acute Massive Pulmonary Embolism Treated With Endovascular Mechanical Fragmentation and Thrombolytic Therapy / Dabigatran Etexilate / Pulmonary Embolism (PE) / Recurrence of DVT / Warfarin1
4RecruitingTreatmentAnticoagulating Treatment on a Duration at Least 12-month-old Superior / Anticoagulation Treatment at Least > or = to 12-month / Permanent Atrial Fibrillation / Pulmonary Embolism (PE) / Thrombosis, Venous1
4RecruitingTreatmentAortic Valve Disorder / Aortic Valve Insufficiency / Aortic Valve Stenosis / Regurgitation, Aortic Valve1
4RecruitingTreatmentCoronary Artery Disease / Nonvalvular Atrial Fibrillation2
4RecruitingTreatmentDiabetes Mellitus (DM)1
4RecruitingTreatmentLiver Cirrhosis / Portal Vein Thrombosis1
4RecruitingTreatmentNonvalvular Atrial Fibrillation / Valve Heart Disease1
4TerminatedOtherCoronary Artery Bypass Graft Surgery Patients / Presence of Heparin/Platelet Factor 4 Antibody1
4TerminatedTreatmentHematoma1
4TerminatedTreatmentNonvalvular Atrial Fibrillation1
4TerminatedTreatmentPulmonary Embolism (PE) / Thrombosis, Venous1
4TerminatedTreatmentVenous Thromboembolism (VTE)1
4Unknown StatusNot AvailableHeart Valve Disease / Nonvalvular Atrial Fibrillation / Pulmonary Artery Embolism1
4Unknown StatusPreventionComplications Due to Heart Valve Prosthesis1
4Unknown StatusTreatmentNonvalvular Atrial Fibrillation1
4WithdrawnPreventionChronic Kidney Disease (CKD) / Nonvalvular Atrial Fibrillation1
4WithdrawnTreatmentComplications; Arthroplasty1
4WithdrawnTreatmentDisorders, Blood Coagulation1
4WithdrawnTreatmentMitral Valve Stenosis / Nonvalvular Atrial Fibrillation1
Not AvailableActive Not RecruitingNot AvailableNon-valvular Atrial Fibrillation (NVAF)1
Not AvailableActive Not RecruitingNot AvailableNonvalvular Atrial Fibrillation3
Not AvailableActive Not RecruitingNot AvailableNonvalvular Atrial Fibrillation / Thrombus Due to Heart Valve Prosthesis1
Not AvailableActive Not RecruitingTreatmentCardiovascular Disease (CVD) / Heart Failure1
Not AvailableCompletedNot AvailableAnticoagulation1
Not AvailableCompletedNot AvailableAtrial Fibrillation and Flutter1
Not AvailableCompletedNot AvailableHeart Valve Disease1
Not AvailableCompletedNot AvailableMajor Bleeding / Myocardial Infarction / Nonvalvular Atrial Fibrillation / Stroke, Ischemic / Systemic Embolization / The Mortality Rate1
Not AvailableCompletedNot AvailableMajor Bleeding / Venous Thromboembolism (VTE)1
Not AvailableCompletedNot AvailableNonvalvular Atrial Fibrillation8
Not AvailableCompletedNot AvailableNonvalvular Atrial Fibrillation / Strokes Thrombotic1
Not AvailableCompletedNot AvailableStroke, Ischemic1
Not AvailableCompletedNot AvailableUnsuspected Pulmonary Embolism1
Not AvailableCompletedBasic ScienceDrug Drug Interaction (DDI) / Healthy Volunteers / Warfarin1
Not AvailableCompletedBasic ScienceHealthy Volunteers2
Not AvailableCompletedBasic SciencePharmacokinetics1
Not AvailableCompletedPreventionBradycardia / Nonvalvular Atrial Fibrillation / Tachycardia / Valvular Heart Disease1
Not AvailableCompletedPreventionCardiac Pacing / Complications / Thrombosis, Venous1
Not AvailableCompletedSupportive CareThromboembolism1
Not AvailableCompletedTreatmentAnticoagulation1
Not AvailableCompletedTreatmentDeep Vein Thrombosis (DVT) / Nonvalvular Atrial Fibrillation / Pulmonary Embolism (PE)2
Not AvailableCompletedTreatmentMetachromatic Leukodystrophy1
Not AvailableCompletedTreatmentMyocardial Infarction1
Not AvailableCompletedTreatmentNonvalvular Atrial Fibrillation1
Not AvailableEnrolling by InvitationNot AvailableDeep Venous Thrombosis / Pulmonary Embolism (PE)1
Not AvailableEnrolling by InvitationOtherCardiovascular Disease (CVD) / Heart Failure1
Not AvailableEnrolling by InvitationTreatmentAnticoagulant Adverse Reaction / Hemorrhage / Nonvalvular Atrial Fibrillation / Thrombotic events1
Not AvailableEnrolling by InvitationTreatmentCardiovascular Disease (CVD) / Heart Failure1
Not AvailableNot Yet RecruitingNot AvailableChronic Kidney Disease (CKD) / Nonvalvular Atrial Fibrillation1
Not AvailableNot Yet RecruitingNot AvailableNonvalvular Atrial Fibrillation1
Not AvailableNot Yet RecruitingNot AvailablePoor Drug Response1
Not AvailableNot Yet RecruitingPreventionHemorrhage, Gastrointestinal / Post Polypectomy Bleeding in Anticoagulated Patients1
Not AvailableNot Yet RecruitingTreatmentLeft Atrial Appendage Thrombosis / Nonvalvular Atrial Fibrillation / Rivaroxaban1
Not AvailableRecruitingNot AvailableAcute Bacterial Exacerbation of Chronic Bronchitis (ABECB) / Acute Bacterial Sinusitis (ABS) / Acute Decompensated Heart Failure (ADHF) / Acute Pyelonephritis / Adenovirus / Adjunct to general anesthesia therapy / Adrenal Insufficiency / Airway Swelling / Anaesthesia therapy / Anxiety / Anxiolysis / Arterial Hypotension / Autism, Early Infantile / Autistic Disorder / Bartonellosis / Benzodiazepine Withdrawal / Benzodiazepines / Bipolar Disorder (BD) / Bloodstream Infections / Bone and Joint Infections / Bradycardia / Brain Swelling / Bronchospasm / Brucellosis / Cardiac Arrest / Cardiac Dysrhythmia / Central Nervous System Infections / Cholera / Chronic Bacterial Prostatitis / Chronic Kidney Disease (CKD) / Community Acquired Pneumonia (CAP) / Complicated Urinary Tract Infections / Convulsions / Cytomegalovirus Retinitis / Drug hypersensitivity reaction / Early-onset Schizophrenia Spectrum Disorders / Endocarditis / Epilepsies / Fibrinolytic Bleeding / Flu caused by Influenza / Gastroparesis / Gram-negative Infection / Gynaecological infection / Headaches / Heart Failure / Heavy Menstrual Bleeding / Hemophilia / Herpes Simplex Virus / High Blood Pressure (Hypertension) / High Cholesterol / Hospital-acquired bacterial pneumonia / Hyperaldosteronism / Hyperlipidemias / Hypokalaemia / Infantile Hemangiomas / Infection caused by staphylococci / Infection NOS / Inflammatory Conditions / Inflammatory Reaction / Influenza Treatment or Prophylaxis / Inhalational Anthrax (Post-Exposure) / Intra-Abdominal Infections / Life-threatening Fungal Infections / Lower Respiratory Tract Infection (LRTI) / Meningitis, Bacterial / Methicillin Resistant Staphylococcus Aureus (MRSA) / Migraine / Muscle Spasms / Nausea / Neuromuscular Blockade / Neutropenias / Oedema / Opioid Addiction / Pain NOS / Plague / Pneumonia / Prophylaxis / Psittacosis / Pulmonary Arterial Hypertension (PAH) / Q Fever / Reflux / Relapsing Fever / Rocky Mountain Spotted Fever / Schizophrenic Disorders / Sedation therapy / Seizures / Sepsis / Skeletal Muscle Spasms / Skin and Subcutaneous Tissue Bacterial Infections / Skin Structures and Soft Tissue Infections / Sleeplessness / Stable Angina (SA) / Thromboprophylaxis / Thrombotic events / Toxic effect of hydrocyanic acid and cyanides / Trachoma / Treatment-resistant Schizophrenia / Tularemia / Typhus Fever / Uncomplicated Skin and Skin Structure Infections / Uncomplicated Urinary Tract Infections / Urinary Tract Infections (UTIs) / Vomiting / Withdrawal1
Not AvailableRecruitingNot AvailableAcute Coronary Syndromes (ACS) / Nonvalvular Atrial Fibrillation / Pulmonary Embolism (PE) / Thrombosis, Venous1
Not AvailableRecruitingNot AvailableAnticoagulants and Bleeding Disorders / Venous Thromboembolism (VTE)1
Not AvailableRecruitingNot AvailableCoronary Artery Disease / Haemorrhage foetal / Nonvalvular Atrial Fibrillation / Strokes1
Not AvailableRecruitingNot AvailableNonvalvular Atrial Fibrillation2
Not AvailableRecruitingNot AvailableNonvalvular Atrial Fibrillation / Strokes / Systemic Embolism1
Not AvailableRecruitingNot AvailablePulmonary Arterial Hypertension (PAH)1
Not AvailableRecruitingOtherHealthy Volunteers1
Not AvailableRecruitingPreventionAnticoagulants; Increased / Valve Heart Disease1
Not AvailableRecruitingSupportive CareHemorrhage / Nonvalvular Atrial Fibrillation / Periodontal Diseases1
Not AvailableRecruitingTreatmentAcute DVT of Lower Extremity1
Not AvailableRecruitingTreatmentAcute Exacerbation of Chronic Obstructive Pulmonary Disease / PE - Pulmonary Thromboembolism1
Not AvailableRecruitingTreatmentBlood Clots / Deep Vein Thrombosis (DVT) / Malignancies / Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)1
Not AvailableRecruitingTreatmentDeep Venous Thrombosis1
Not AvailableRecruitingTreatmentLiver Cirrhosis / Portal Vein Thrombosis1
Not AvailableRecruitingTreatmentNonvalvular Atrial Fibrillation1
Not AvailableRecruitingTreatmentNonvalvular Atrial Fibrillation / Pulmonary Embolism (PE) / Thrombosis, Venous1
Not AvailableRecruitingTreatmentProsthetic Valve Thrombosis1
Not AvailableTerminatedNot AvailablePrescribers' Drug Orders1
Not AvailableTerminatedDiagnosticAortic Valve Disorder1
Not AvailableTerminatedTreatmentVenous Thromboembolism (VTE)1
Not AvailableUnknown StatusNot AvailableCardiac Thrombus / Cardiomyopathy (Ischemic or Dilated) / Deep Vein Thrombosis (DVT) / Heart Valve Replacement (Mechanical or Biological With AF) / Nonvalvular Atrial Fibrillation / Peripheral Vascular Disease (PVD) / Pulmonary Embolism (PE)1
Not AvailableUnknown StatusNot AvailableStroke, Ischemic1
Not AvailableUnknown StatusTreatmentDeep Venous Thromboembolism1
Not AvailableUnknown StatusTreatmentCardiac valve replacement / Deep Venous Thrombosis / Nonvalvular Atrial Fibrillation / Pulmonary Embolism (PE)1
Not AvailableUnknown StatusTreatmentHeart; Complications, Valve, Prosthesis / Pregnancy1
Not AvailableUnknown StatusTreatmentIleofemoral Deep Vein Thrombosis1
Not AvailableUnknown StatusTreatmentPulmonary Embolism (PE)1
Not AvailableUnknown StatusTreatmentThrombotic events1
Not AvailableWithdrawnTreatmentAnticoagulation / Liver Cirrhosis / Portal Vein Thrombosis1

Pharmacoeconomics

Manufacturers
  • Pharmaceutical research assoc inc
  • Bristol myers squibb pharma co
  • Usl pharma inc
  • Abbott laboratories pharmaceutical products div
  • Barr laboratories inc
  • Mylan pharmaceuticals inc
  • Pliva inc
  • Sandoz inc
  • Taro pharmaceuticals inc
  • Watson laboratories inc
  • Zydus pharmaceuticals usa inc
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Apothecon
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Barr Pharmaceuticals
  • Blenheim Pharmacal
  • Bristol-Myers Squibb Co.
  • Cadila Healthcare Ltd.
  • Cardinal Health
  • Caremark LLC
  • Coastal Family Health Center Inc.
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Genpharm LP
  • Heartland Repack Services LLC
  • Ipca Laboratories Ltd.
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Mallinckrodt Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Neuman Distributors Inc.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • Spectrum Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Scripts LLC
  • Taro Pharmaceuticals USA
  • Tya Pharmaceuticals
  • Upsher Smith Laboratories
  • USL Pharma Inc.
  • Va Cmop Dallas
  • Vangard Labs Inc.
  • Zydus Pharmaceuticals
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous2 mg/1mL
Powder, for solutionIntravenous5 mg
TabletOral
TabletOral1 mg/1
TabletOral10 mg/1
TabletOral2 mg/1
TabletOral2.5 mg/1
TabletOral3 mg/1
TabletOral4 mg/1
TabletOral5 mg/1
TabletOral6 mg/1
TabletOral7.5 ug/1
TabletOral7.5 mg/1
Prices
Unit descriptionCostUnit
Warfarin sodium powder54.53USD g
Coumadin 5 mg vial34.07USD vial
Coumadin 10 mg tablet2.01USD tablet
Coumadin 7.5 mg tablet1.97USD tablet
Coumadin 6 mg tablet1.94USD tablet
Coumadin 3 mg tablet1.51USD tablet
Coumadin 5 mg tablet1.51USD tablet
Coumadin 4 mg tablet1.49USD tablet
Coumadin 2.5 mg tablet1.46USD tablet
Coumadin 2 mg tablet1.4USD tablet
Coumadin 1 mg tablet1.37USD tablet
Warfarin sodium 10 mg tablet1.0USD tablet
Warfarin sodium 7.5 mg tablet0.96USD tablet
Jantoven 10 mg tablet0.76USD tablet
Jantoven 7.5 mg tablet0.74USD tablet
Jantoven 6 mg tablet0.72USD tablet
Warfarin sodium 6 mg tablet0.68USD tablet
Warfarin sodium 3 mg tablet0.66USD tablet
Warfarin sodium 4 mg tablet0.66USD tablet
Warfarin sodium 2.5 mg tablet0.65USD tablet
Warfarin sodium 5 mg tablet0.65USD tablet
Warfarin sodium 2 mg tablet0.63USD tablet
Warfarin sodium 1 mg tablet0.61USD tablet
Jantoven 5 mg tablet0.59USD tablet
Jantoven 2 mg tablet0.56USD tablet
Jantoven 4 mg tablet0.56USD tablet
Jantoven 2.5 mg tablet0.53USD tablet
Jantoven 3 mg tablet0.53USD tablet
Coumadin 10 mg Tablet0.5USD tablet
Jantoven 1 mg tablet0.49USD tablet
Coumadin 3 mg Tablet0.43USD tablet
Coumadin 4 mg Tablet0.43USD tablet
Coumadin 2 mg Tablet0.35USD tablet
Coumadin 1 mg Tablet0.33USD tablet
Taro-Warfarin 7.5 mg Tablet0.33USD tablet
Taro-Warfarin 6 mg Tablet0.31USD tablet
Apo-Warfarin 10 mg Tablet0.28USD tablet
Coumadin 2.5 mg Tablet0.28USD tablet
Coumadin 5 mg Tablet0.28USD tablet
Mylan-Warfarin 10 mg Tablet0.28USD tablet
Taro-Warfarin 10 mg Tablet0.28USD tablet
Warfarin 10 mg Tablet0.28USD tablet
Apo-Warfarin 3 mg Tablet0.24USD tablet
Apo-Warfarin 4 mg Tablet0.24USD tablet
Mylan-Warfarin 3 mg Tablet0.24USD tablet
Mylan-Warfarin 4 mg Tablet0.24USD tablet
Novo-Warfarin 3 mg Tablet0.24USD tablet
Novo-Warfarin 4 mg Tablet0.24USD tablet
Taro-Warfarin 3 mg Tablet0.24USD tablet
Taro-Warfarin 4 mg Tablet0.24USD tablet
Warfarin 3 mg Tablet0.24USD tablet
Warfarin 4 mg Tablet0.24USD tablet
Apo-Warfarin 2 mg Tablet0.19USD tablet
Mylan-Warfarin 2 mg Tablet0.19USD tablet
Novo-Warfarin 2 mg Tablet0.19USD tablet
Taro-Warfarin 2 mg Tablet0.19USD tablet
Warfarin 2 mg Tablet0.19USD tablet
Apo-Warfarin 1 mg Tablet0.18USD tablet
Mylan-Warfarin 1 mg Tablet0.18USD tablet
Novo-Warfarin 1 mg Tablet0.18USD tablet
Taro-Warfarin 1 mg Tablet0.18USD tablet
Warfarin 1 mg Tablet0.18USD tablet
Apo-Warfarin 5 mg Tablet0.16USD tablet
Mylan-Warfarin 5 mg Tablet0.16USD tablet
Novo-Warfarin 5 mg Tablet0.16USD tablet
Taro-Warfarin 5 mg Tablet0.16USD tablet
Warfarin 5 mg Tablet0.16USD tablet
Apo-Warfarin 2.5 mg Tablet0.15USD tablet
Mylan-Warfarin 2.5 mg Tablet0.15USD tablet
Novo-Warfarin 2.5 mg Tablet0.15USD tablet
Taro-Warfarin 2.5 mg Tablet0.15USD tablet
Warfarin 2.5 mg Tablet0.15USD tablet
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Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)161 °CPhysProp
water solubility17 mg/L (at 20 °C)TOMLIN,C (1997)
logP2.70HANSCH,C ET AL. (1995)
logS-3.89ADME Research, USCD
Caco2 permeability-4.68ADME Research, USCD
pKa5.0UFER, M (2005)
Predicted Properties
PropertyValueSource
Water Solubility0.0472 mg/mLALOGPS
logP2.41ALOGPS
logP2.74ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)6.33ChemAxon
pKa (Strongest Basic)-6.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.6 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity86.86 m3·mol-1ChemAxon
Polarizability31.93 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9109
Blood Brain Barrier+0.9124
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.5502
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.8863
CYP450 2C9 substrateNon-substrate0.678
CYP450 2D6 substrateSubstrate0.5658
CYP450 3A4 substrateNon-substrate0.6007
CYP450 1A2 substrateNon-inhibitor0.714
CYP450 2C9 inhibitorInhibitor0.7657
CYP450 2D6 inhibitorNon-inhibitor0.9286
CYP450 2C19 inhibitorNon-inhibitor0.9161
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8785
Ames testNon AMES toxic0.6844
CarcinogenicityNon-carcinogens0.9352
BiodegradationNot ready biodegradable0.7474
Rat acute toxicity4.1700 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8768
hERG inhibition (predictor II)Non-inhibitor0.9615
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (8.72 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-014i-0293000000-848341bcbd6a3f0a2c6b
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0429000000-1e818b579dc7a0fade2d
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-0900000000-f568338c06cd9b4762ac
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-0900000000-acdd0ed19e403aa73c77
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0bt9-0539000000-5b1c7c6c812ba72325e3
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0009000000-e461e1aca7977a2838ad
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0w29-0960000000-9fa099190280529cd891
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00di-0910000000-d7dbaf6e7b34ee85e1f7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0920000000-4fb886a5c160afa86df9
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0920000000-ad608fe7680a2adf9d90
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0ik9-0942000000-5864f2d15892753d6a8b

Taxonomy

Description
This compound belongs to the class of organic compounds known as 4-hydroxycoumarins. These are coumarins that contain one or more hydroxyl groups attached to C4-position the coumarin skeleton.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Coumarins and derivatives
Sub Class
Hydroxycoumarins
Direct Parent
4-hydroxycoumarins
Alternative Parents
1-benzopyrans / Pyranones and derivatives / Benzene and substituted derivatives / Vinylogous acids / Heteroaromatic compounds / Lactones / Ketones / Oxacyclic compounds / Organic oxides / Hydrocarbon derivatives
Substituents
4-hydroxycoumarin / Benzopyran / 1-benzopyran / Pyranone / Monocyclic benzene moiety / Benzenoid / Pyran / Heteroaromatic compound / Vinylogous acid / Ketone
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
methyl ketone, hydroxycoumarin (CHEBI:87732) / Coumarin rodenticides (C01541)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vitamin-k-epoxide reductase (warfarin-sensitive) activity
Specific Function
Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the...
Gene Name
VKORC1
Uniprot ID
Q9BQB6
Uniprot Name
Vitamin K epoxide reductase complex subunit 1
Molecular Weight
18234.3 Da
References
  1. Gebauer M: Synthesis and structure-activity relationships of novel warfarin derivatives. Bioorg Med Chem. 2007 Mar 15;15(6):2414-20. Epub 2007 Jan 17. [PubMed:17275317]
  2. Zhu Y, Shennan M, Reynolds KK, Johnson NA, Herrnberger MR, Valdes R Jr, Linder MW: Estimation of warfarin maintenance dose based on VKORC1 (-1639 G>A) and CYP2C9 genotypes. Clin Chem. 2007 Jul;53(7):1199-205. Epub 2007 May 17. [PubMed:17510308]
  3. Yin T, Miyata T: Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1 - rationale and perspectives. Thromb Res. 2007;120(1):1-10. Epub 2006 Dec 11. [PubMed:17161452]
  4. Osman A, Enstrom C, Lindahl TL: Plasma S/R ratio of warfarin co-varies with VKORC1 haplotype. Blood Coagul Fibrinolysis. 2007 Apr;18(3):293-6. [PubMed:17413769]
  5. Limdi NA, McGwin G, Goldstein JA, Beasley TM, Arnett DK, Adler BK, Baird MF, Acton RT: Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African-American and European-American patients on warfarin. Clin Pharmacol Ther. 2008 Feb;83(2):312-21. Epub 2007 Jul 25. [PubMed:17653141]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Curator comments
Only S-enantiomer results in activation.
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Rulcova A, Prokopova I, Krausova L, Bitman M, Vrzal R, Dvorak Z, Blahos J, Pavek P: Stereoselective interactions of warfarin enantiomers with the pregnane X nuclear receptor in gene regulation of major drug-metabolizing cytochrome P450 enzymes. J Thromb Haemost. 2010 Dec;8(12):2708-17. doi: 10.1111/j.1538-7836.2010.04036.x. [PubMed:20735727]

Enzymes

Details
1. Cytochrome P450 2C9
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Daly AK, Rettie AE, Fowler DM, Miners JO: Pharmacogenomics of CYP2C9: Functional and Clinical Considerations. J Pers Med. 2017 Dec 28;8(1). pii: jpm8010001. doi: 10.3390/jpm8010001. [PubMed:29283396]
  2. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [PubMed:16372822]
  3. Rulcova A, Prokopova I, Krausova L, Bitman M, Vrzal R, Dvorak Z, Blahos J, Pavek P: Stereoselective interactions of warfarin enantiomers with the pregnane X nuclear receptor in gene regulation of major drug-metabolizing cytochrome P450 enzymes. J Thromb Haemost. 2010 Dec;8(12):2708-17. doi: 10.1111/j.1538-7836.2010.04036.x. [PubMed:20735727]
  4. Flockhart Table of Drug Interactions [Link]
  5. Warfarin FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Fulco PP, Zingone MM, Higginson RT: Possible antiretroviral therapy-warfarin drug interaction. Pharmacotherapy. 2008 Jul;28(7):945-9. doi: 10.1592/phco.28.7.945. [PubMed:18576910]
  3. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [PubMed:16372822]
  4. FDA label warfarin [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Brandon EF, Meijerman I, Klijn JS, den Arend D, Sparidans RW, Lazaro LL, Beijnen JH, Schellens JH: In-vitro cytotoxicity of ET-743 (Trabectedin, Yondelis), a marine anti-cancer drug, in the Hep G2 cell line: influence of cytochrome P450 and phase II inhibition, and cytochrome P450 induction. Anticancer Drugs. 2005 Oct;16(9):935-43. [PubMed:16162970]
  3. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [PubMed:16372822]
  4. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [PubMed:16372822]
  3. Rulcova A, Prokopova I, Krausova L, Bitman M, Vrzal R, Dvorak Z, Blahos J, Pavek P: Stereoselective interactions of warfarin enantiomers with the pregnane X nuclear receptor in gene regulation of major drug-metabolizing cytochrome P450 enzymes. J Thromb Haemost. 2010 Dec;8(12):2708-17. doi: 10.1111/j.1538-7836.2010.04036.x. [PubMed:20735727]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
  3. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [PubMed:16372822]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C18
Uniprot ID
P33260
Uniprot Name
Cytochrome P450 2C18
Molecular Weight
55710.075 Da
References
  1. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [PubMed:16372822]
  2. Lee MT, Chen CH, Chou CH, Lu LS, Chuang HP, Chen YT, Saleem AN, Wen MS, Chen JJ, Wu JY, Chen YT: Genetic determinants of warfarin dosing in the Han-Chinese population. Pharmacogenomics. 2009 Dec;10(12):1905-13. doi: 10.2217/pgs.09.106. [PubMed:19958090]
  3. Wadelius M, Chen LY, Eriksson N, Bumpstead S, Ghori J, Wadelius C, Bentley D, McGinnis R, Deloukas P: Association of warfarin dose with genes involved in its action and metabolism. Hum Genet. 2007 Mar;121(1):23-34. doi: 10.1007/s00439-006-0260-8. Epub 2006 Oct 18. [PubMed:17048007]

Carriers

Details
1. Serum albumin
Kind
Protein
Organism
Humans
Pharmacological action
No
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Yamasaki K, Maruyama T, Kragh-Hansen U, Otagiri M: Characterization of site I on human serum albumin: concept about the structure of a drug binding site. Biochim Biophys Acta. 1996 Jul 18;1295(2):147-57. [PubMed:8695640]
  2. Joseph KS, Hage DS: The effects of glycation on the binding of human serum albumin to warfarin and L-tryptophan. J Pharm Biomed Anal. 2010 Nov 2;53(3):811-8. doi: 10.1016/j.jpba.2010.04.035. Epub 2010 May 6. [PubMed:20537832]
  3. Wybranowski T, Cyrankiewicz M, Ziomkowska B, Kruszewski S: The HSA affinity of warfarin and flurbiprofen determined by fluorescence anisotropy measurements of camptothecin. Biosystems. 2008 Dec;94(3):258-62. doi: 10.1016/j.biosystems.2008.05.034. Epub 2008 Jul 31. [PubMed:18721856]
  4. Bertucci C, Wainer IW: Improved chromatographic performance of a modified human albumin based stationary phase. Chirality. 1997;9(4):335-40. [PubMed:9275312]
Kind
Protein
Organism
Humans
Pharmacological action
No
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Hazai E, Visy J, Fitos I, Bikadi Z, Simonyi M: Selective binding of coumarin enantiomers to human alpha1-acid glycoprotein genetic variants. Bioorg Med Chem. 2006 Mar 15;14(6):1959-65. Epub 2005 Nov 15. [PubMed:16290938]
  2. Nakagawa T, Kishino S, Itoh S, Sugawara M, Miyazaki K: Differential binding of disopyramide and warfarin enantiomers to human alpha(1)-acid glycoprotein variants. Br J Clin Pharmacol. 2003 Dec;56(6):664-9. [PubMed:14616427]

Drug created on June 13, 2005 07:24 / Updated on October 13, 2019 23:23