Warfarin


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 anticoagulan...

Read more

Pharmacology

Indication

**Indicated** for:[label, Read more

Pharmacodynamic

Warfarin is an anticoagulant, as such it disrupts the coagulation cascade to reduce frequency and ex... Read more

Mechanism of action

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

Absorption

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

Protein binding

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

Volume of distribution

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

Clearance

Clearance of warfarin varies depending on CYP2C9 genotype.[label, Read more

Half life

R-warfarin is cleared more slowly than S-warfarin, at about half the rate.[label] T1/2 fo... Read more

Route of elimination

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

Toxicity

**LD50 Values**

Mouse: 3 mg/kg (Oral), 165 mg/kg (IV), 750 mg/kg (IP)[
Read more


Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Hemorrhage US
Varying Reports
Cholestatic hepatitis US
Varying Reports
Chills US
Varying Reports
Tracheal/tracheobronchial calcification US
Varying Reports
Alopecia US
Varying Reports
Pruritus US
Varying Reports
Dermatitis US
Varying Reports
Bloating US
Varying Reports
Rash US
Varying Reports
Abdominal Pain US
Varying Reports
Flatulence US
Varying Reports
Diarrhea US
Varying Reports
Taste perversion US
Varying Reports
Nausea US
Varying Reports
Vomiting US
Varying Reports
Hepatitis US
Varying Reports
Elevated Liver Enzymes US
Varying Reports
Hypersensitivity/allergic reactions US
Varying Reports
Vasculitis US
Varying Reports
Systemic atheroemboli US
Varying Reports
Cholesterol microemboli US
Varying Reports
Necrosis of skin and other tissues US
Varying Reports
Calciphylaxis US
Varying Reports

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 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.

Interactions

Type in a drug name to check for interaction with Warfarin

(1,2,6,7-3H)Testosterone may increase the anticoagulant activities of Warfarin.
The metabolism of Warfarin can be increased when combined with (R)-warfarin.
The metabolism of Warfarin can be increased when combined with (S)-Warfarin.
1-Testosterone may increase the anticoagulant activities of Warfarin.
18-methyl-19-nortestosterone may increase the anticoagulant activities of Warfarin.
The risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Warfarin.
The risk or severity of bleeding can be increased when 25-desacetylrifapentine is combined with Warfarin.
The metabolism of Warfarin can be decreased when combined with 3,5-diiodothyropropionic acid.
3,5-Diiodotyrosine may increase the anticoagulant activities of Warfarin.
The risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Warfarin.
The metabolism of 4-hydroxycoumarin can be increased when combined with Warfarin.
4-Hydroxytestosterone may increase the anticoagulant activities of Warfarin.
The metabolism of Warfarin can be decreased when combined with 5-androstenedione.
The risk or severity of bleeding can be increased when 5-fluorouridine is combined with Warfarin.
The risk or severity of adverse effects can be increased when 5-methoxy-N,N-dimethyltryptamine is combined with Warfarin.
5beta-dihydrotestosterone may increase the anticoagulant activities of Warfarin.
The serum concentration of Warfarin can be increased when it is combined with 6-Deoxyerythronolide B.
The metabolism of Warfarin can be decreased when combined with 6-O-benzylguanine.
The serum concentration of Warfarin can be increased when it is combined with 7-ethyl-10-hydroxycamptothecin.
The risk or severity of bleeding and hemorrhage can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Warfarin.

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.
  • 17 . Warfarin DPD Monograph [Link]
  • 18 . ChemIDplus: Warfarin [Link]
  • 19 . HSDB: Warfarin [Link]
  • 20 . LactMed: Warfarin [Link]

Recent Questions