Description

Simple

A medication used to prevent the formation of blood clots in the body.

Clinical

A vitamin K antagonist used to treat venous thromboembolism, pulmonary embolism, thromboembolism with atrial fibrillation, thromboembolism with cardiac valve replacement, and thromboembolic events post myocardial infarction.

Overview

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.

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) Pro... Read more

Pharmacodynamic

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 incre... Read more

Mechanism of action

Warfarin is a [vitamin K] antagonist which acts to inhibit the production of vitamin K by vitamin K epoxide reductase.[label, Read more

Absorption

Completely absorbed from the GI tract. The mean Tmax for warfarin sodium tablets is 4 hours.[label,17, Read more

Protein binding

99% bound primarily to albumin.[label,17, Read more

Volume of distribution

Vd of 0.14 L/kg.[label,17, Read more

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 clea... Read more

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.

Route of elimination

The elimination of warfarin is almost entirely by metabolism with a small amount excreted unchanged.[label,17, Read more

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)[ Read more

Adverse Effects

Contraindications

  • Regions: Canada
  • Patient Conditions:
      • Name: Inadequate access to laboratory facilities
      • Drugbank Id: DBCOND0120034
  • Regions: US
  • Patient Conditions:
      • Name: High risk Patient Non-Compliance
      • Drugbank Id: DBCOND0120033
      • Modification Of:
        • Base:
          • Name: Patient Non-Compliance
          • Drugbank Id: DBCOND0052440
        • Severity:
          • Includes:
            • high risk
  • Sex Group: female
  • Regions: US
  • Patient Conditions:
      • Name: Without mechanical heart valve
      • Drugbank Id: DBCOND0120032
      • Name: Pregnancy
      • Drugbank Id: DBCOND0018394
  • Regions: US
  • With Therapies:
      • Name: Procedure with high risk of uncontrollable bleeding
      • Drugbank Id: DBCOND0120031
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Eclampsia
      • Drugbank Id: DBCOND0000607
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Threatened Abortion
      • Drugbank Id: DBCOND0055352
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Spinal Puncture
      • Drugbank Id: DBCOND0036137
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Preeclampsia
      • Drugbank Id: DBCOND0030912
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Pericarditis
      • Drugbank Id: DBCOND0007278
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Dissecting aorta
      • Drugbank Id: DBCOND0107935
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Bacterial Endocarditis
      • Drugbank Id: DBCOND0031170
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Pericardial effusions
      • Drugbank Id: DBCOND0104153
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Major regional anesthesia
      • Drugbank Id: DBCOND0107937
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Malignant Hypertension
      • Drugbank Id: DBCOND0040156
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Lumbar block anesthesia
      • Drugbank Id: DBCOND0107938
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Gastrointestinal overt bleeding
      • Drugbank Id: DBCOND0107930
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Gastrointestinal active ulceration
      • Drugbank Id: DBCOND0107929
      • Modification Of:
        • Condition Status: active
        • Base:
          • Name: Gastrointestinal ulceration
          • Drugbank Id: DBCOND0096568
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Genitourinary overt bleeding
      • Drugbank Id: DBCOND0107932
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Genitourinary active ulceration
      • Drugbank Id: DBCOND0107931
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Respiratory tract overt bleeding
      • Drugbank Id: DBCOND0107934
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Respiratory tract active ulceration
      • Drugbank Id: DBCOND0107933
      • Modification Of:
        • Condition Status: active
        • Base:
          • Name: Respiratory tract ulceration
          • Drugbank Id: DBCOND0019531
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Cerebral Aneurysms
      • Drugbank Id: DBCOND0045021
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Central nervous system hemorrhage
      • Drugbank Id: DBCOND0102385
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Surgery of the central nervous system
      • Drugbank Id: DBCOND0107924
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Traumatic surgery resulting
      • Drugbank Id: DBCOND0107926
      • Name: Large open surfaces
      • Drugbank Id: DBCOND0107927
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Surgery of the eye
      • Drugbank Id: DBCOND0107925
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Blood dyscrasias
      • Drugbank Id: DBCOND0095746
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Hemorrhagic tendencies
      • Drugbank Id: DBCOND0107928

Food Interactions

  • Avoid alcohol.
  • Avoid drastic dietary changes.
  • Avoid foods rich in vitamin K. Vitamin K in foods such as leafy vegetables can reduce warfarin efficacy.
  • Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, and ginkgo.
  • Avoid St. John's Wort.

Interactions

Type in a drug name to check for interaction with Warfarin
Type a drug name in the box above to get started
  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(1,2,6,7-3H)Testosterone
(1,2,6,7-3H)Testosterone may increase the anticoagulant activities of Warfarin.
(R)-warfarin
The metabolism of Warfarin can be increased when combined with (R)-warfarin.
(S)-Warfarin
The metabolism of Warfarin can be increased when combined with (S)-Warfarin.
1-Testosterone
1-Testosterone may increase the anticoagulant activities of Warfarin.
18-methyl-19-nortestosterone
18-methyl-19-nortestosterone may increase the anticoagulant activities of Warfarin.
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Warfarin.
25-desacetylrifapentine
The risk or severity of bleeding can be increased when 25-desacetylrifapentine is combined with Warfarin.
3,5-Diiodotyrosine
3,5-Diiodotyrosine may increase the anticoagulant activities of Warfarin.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Warfarin.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be increased when combined with Warfarin.
4-Hydroxytestosterone
4-Hydroxytestosterone may increase the anticoagulant activities of Warfarin.
5-fluorouridine
The risk or severity of bleeding can be increased when 5-fluorouridine is combined with Warfarin.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of adverse effects can be increased when 5-methoxy-N,N-dimethyltryptamine is combined with Warfarin.
5beta-dihydrotestosterone
5beta-dihydrotestosterone may increase the anticoagulant activities of Warfarin.
6-Deoxyerythronolide B
The serum concentration of Warfarin can be increased when it is combined with 6-Deoxyerythronolide B.
6-O-benzylguanine
The metabolism of 6-O-benzylguanine can be decreased when combined with Warfarin.
7-ethyl-10-hydroxycamptothecin
The serum concentration of Warfarin can be increased when it is combined with 7-ethyl-10-hydroxycamptothecin.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
The risk or severity of bleeding and hemorrhage can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Warfarin.
8-azaguanine
The metabolism of 8-azaguanine can be decreased when combined with Warfarin.
8-chlorotheophylline
The metabolism of 8-chlorotheophylline can be decreased when combined with Warfarin.
20 References
  1. 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. 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. 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. 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. 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. 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. 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. 8 . Freedman MD: Oral anticoagulants: pharmacodynamics, clinical indications and adverse effects. J Clin Pharmacol. 1992 Mar;32(3):196-209.PubMed: 1564123
  9. 9 . Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46.PubMed: 16372822
  10. 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. 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. 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. 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. 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. 15 . Aster JC, Bunn HF (2017). Pathophysiology of Blood Disorders (2nd ed.). McGraw-Hill.
  16. 16 . Brunton LL, Hilal-Dandan R, Knollmann BC. eds (2018). Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education.
  17. 17 . Warfarin DPD Monograph Link
  18. 18 . ChemIDplus: Warfarin Link
  19. 19 . HSDB: Warfarin Link
  20. 20 . LactMed: Warfarin Link