Table of contents

  • Brand Names
  • Chemistry
  • Pharmacologic Category
  • Mechanism of Action
  • Therapeutic Use
  • Unlabeled Use
  • Pregnancy and Lactation Implications
  • Contraindications
  • Warnings and Precautions
  • Adverse Reactions
  • Caution and personalized dose adjustment in patients with the following genotypes
  • Other genes that may be involved
  • Substrate of
  • Inhibits
  • Induces
  • Drug Interactions
  • Nutrition/Nutraceutical Interactions
  • Dosage
  • Pharmacokinetics and Pharmacodynamics
  • Special Considerations

Brand Names


Belgium: Marevan; Cyprus: Coumadin; Czech Republic: Lawarin, Warfarin; Denmark: Marevan; Estonia: Marevan; Finland: Marevan, Warfarin; France: Coumadine; Germany: Coumadin; Greece: Panwarfin, Warfarin, Warfin; Hungary: Marfagen, Warfarin; Ireland: Warfant, Warfarin; Italy: Coumadin; Latvia: Warfarin; Lithuania: Warfarin; Luxembourg: Marevane; Poland: Warfin; Portugal: Varfine; Slovakia: Lawarin, Warfarin; Spain: Aldocumar; Sweden: Waran, Warfarin; UK: Marevan, Warfarin.

North America

Canada: Coumadin, Warfarin; USA: Coumadin, Jantoven, Warfarin.

Latin America

Argentina: Circuvit, Coumadín; Brazil: Coumadin, Marevan, Varfarina; Mexico: Coumadín.


Japan: Arefarin, Samofaron, Warfarin, Warlin.

Drug combinations


Warfarin Sodium: C~19~H~15~NaO~4~. Mw: 330.31. (1) 2H-1-Benzopyran-2-one, 4-hydroxy-3-(3-oxo-1-phenylbutyl)-, sodium salt; (2) 3-(α-Acetonylbenzyl)-4-hydroxycoumarin sodium salt. CAS-129-06-6; CAS-81-81-2 (warfarin).

Pharmacologic Category

Antithrombotic Agents; Anticoagulants; Coumarin Derivatives. Vitamin K Antagonist. (ATC-Code: B01AA03).

Mechanism of action

«Active» vitamin K is oxidatively converted to «inactive» form, then subsequently re-activated by vitamin K epoxide reductase complex 1 (VKORC1). Warfarin competitively inhibits subunit 1 of multi-unit VKOR complex, thus depleting functional vitamin K reserves and hence reduces synthesis of active clotting factors. Antithrombogenic effects generally occur only after functional coagulation factors IX and X are diminished (usually 2-7 days following initiation of therapy). Does not alter catabolism of blood coagulation factors. Inhibits thrombus formation when stasis is induced; may prevent extension of existing thrombi. No direct effect on established thrombi. Little if any effect on platelet-rich arterial thrombi adhering to abnormal vessel wall. Prolongs PT and APTT. Phytonadione (vitamin K~1~) reverses anticoagulant effect.

Therapeutic use

Prophylaxis and treatment of thromboembolic disorders (e.g. venous, pulmonary) and embolic complications arising from atrial fibrillation or cardiac valve replacement. Adjunct for reduction of risk of systemic embolism (e.g. recurrent MI, stroke) after MI.

Pregnancy and lactiation implications

Oral anticoagulants cross placenta and produce fetal abnormalities. May also cause fatal fetal hemorrhage. Warfarin should not be used during pregnancy. Adjusted-dose heparin can be given safely throughout pregnancy in patients with venous thromboembolism. Does not enter breast milk; only metabolites excreted.

Unlabeled use

Prevention of recurrent transient ischemic attacks.


Hypersensitivity to warfarin or any component of the formulation. Hemorrhagic tendencies. Recent or potential surgery of eye or CNS. Major regional lumbar block anesthesia or surgery resulting in large, open surfaces. Blood dyscrasias. Severe uncontrolled or malignant hypertension. Pericarditis or pericardial effusion. Subacute bacterial endocarditis. History of warfarin-induced necrosis. Alcoholism. History of falls or significant fall risk. Unsupervised senile or psychotic patients. Eclampsia/pre-eclampsia, threatened abortion, pregnancy.

Warnings and precautions

May cause hypersensitivity reactions, including anaphylaxis (use with caution in anaphylactic disorders). May cause major or fatal bleeding (risk factors include high-intensity anticoagulation (INR>4), ≥65 years, variable INRs, history of GI bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, severe diabetes, malignancy, trauma, renal insufficiency, polycythemia vera, vasculitis, open wounds, history of peptic ulcer, indwelling catheters, menstruating and postpartum women, drug-drug interactions, long duration of therapy, or known genetic deficiency in CYP2C9 activity). Necrosis or gangrene of skin and other tissue can occur due to paradoxical local thrombosis (higher risk if protein C or S deficiency). Cholesterol microembolization may cause «purple toe» syndrome (a dark, purplish, mottled discoloration of plantar and lateral surfaces), rash, livedo reticularis, gangrene, abrupt and intense pain in lower extremities; abdominal, flank, or back pain, hematuria, renal insufficiency, hypertension, cerebral ischemia, spinal cord infarction, or other symptoms of vascular compromise. Use with caution in prolonged dietary insufficiencies (vitamin K deficiency). Use with caution in heparin-induced thrombocytopenia and deep venous thrombosis; limb ischemia, necrosis, and gangrene occurred when warfarin was started or continued after heparin was stopped. Warfarin monotherapy contraindicated in initial treatment of active heparin-induced thrombocytopenia. Warfarin initially inhibits synthesis of protein C, potentially accelerating underlying active thrombotic process. Reduced liver function may impair synthesis of coagulation factors leading to increased warfarin sensitivity. Use with caution in acute infection or active tuberculosis or any disruption of normal GI flora (antibiotics and fever may alter response to warfarin), in moderate-to-severe renal impairment, and in thyroid disease. The elderly may be more sensitive to anticoagulant therapy. Ovulating women may be at risk of developing ovarian hemorrhage at time of ovulation. Presence of CYP2C9*2 or CYP2C9*3 allele and/or polymorphism of vitamin K oxidoreductase (VKORC1) gene may increase risk of bleeding. Other variant CYP2C9 alleles (e.g. *5, *6, *9, and *11) also associated with reduced metabolic activity and thus may increase risk of bleeding, but are much less common.



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