Warfarin

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warfarin (WOR-fuh-rin)A drug that prevents blood from clotting. It belongs to the family of drugs called anticoagulants (blood thinners). Warfarin is a commonly used oral anticoagulant with anti-vitamin K activity. 

Liver safety of Warfarin

Warfarin therapy is associated with rare instances of idiosyncratic, clinically apparent liver injury that are usually mild and rapidly reversible on stopping.

Mechanism of action of Warfarin

Warfarin (war' far in) was discovered after identification of the hemorrhagic activity that caused toxicity and bleeding in cattle after eating spoiled, sweet clover silage.  Once the active component was shown to be bis-hydroxycoumarin, synthetic derivatives were developed and found to be effective rodenticides.  Only thereafter were coumarin derivatives shown to be useful as Anticoagulants in humans, and only with careful monitoring.  Importantly, coumarin itself does not have anticoagulant activity but is used as an antineoplastic agent, and has different effects and side effects than its derivatives.  Coumarin derivatives include warfarin, dicumarol, phenprocoumon and acenocoumarol.  These compounds act by blocking the enzymatic reduction of vitamin K to its active form, which is responsible for the final steps of synthesis of several clotting factors (Factors II, VII, IX and X).  The coumarin derivatives cause a prolongation of the prothrombin time which is beneficial in preventing progression or recurrence of deep vein thrombosis and pulmonary embolism.  Oral anticoagulation is also used to prevent arterial or venous embolization after acute myocardial infarction, atrial fibrillation and prosthetic heart value placement. 

FDA approval information for Warfarin

Warfarin was approved for use in the United States in 1961 and remains in wide use with more than 30 million prescriptions filled yearly.  The typical dose is 5 mg daily for 2 to 4 days followed by 2 to 10 mg daily, based upon measurements of prothrombin time aiming at an international normalized ratio (INR) value of 2 to 3.  Monitoring of the INR is essential during warfarin therapy, because bleeding is a common side effect and can be life-threatening and fatal. 

Side effects of Warfarin

Side effects not directly attributable to the anticoagulant activity of warfarin are not common, but can include nausea, abdominal discomfort, diarrhea, anorexia, fever, alopecia, skin necrosis and bluish discoloration.  Finally, warfarin is very sensitive to drug-drug interactions involving its metabolism or function and great care must be given to starting or stopping concurrent medications in patients on warfarin therapy.  Severe bleeding episodes can be caused by administration of another medication that prolongs its half-life or activity.


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