Swarfarin

Warfarin is an oral anticoagulant used to prevent and treat thromboembolic disorders. It acts as a vitamin K antagonist, inhibiting the vitamin K epoxide reductase complex (VKORC1). This decreases the hepatic production of vitamin K–dependent clotting factors II, VII, IX, and X, as well as the anticoagulant proteins C and S. The onset of action is delayed because existing clotting factors must expire.

Common indications include atrial fibrillation with risk of stroke, venous thromboembolism such as DVT or PE, and prophylaxis after certain surgeries or in patients with mechanical heart valves. Dosing is individualized and guided by the international normalized ratio (INR); therapeutic ranges vary by condition but commonly fall between 2.0 and 3.0, sometimes higher for mechanical valves.

Warfarin is administered orally; dosing requires regular INR monitoring, especially after starting or changing doses. Consistent dietary intake of vitamin K helps stabilize therapy. Numerous drug interactions exist; antibiotics, antifungals, and anti-seizure medications can affect INR. Severe ill patients require careful management.

Risks include bleeding, which can be serious or life-threatening. Warfarin is teratogenic and contraindicated in pregnancy. Early in therapy, skin necrosis and rarely purple toe syndrome can occur. Reversal is achieved with vitamin K, and in major bleeding with intravenous vitamin K plus prothrombin complex concentrates or fresh frozen plasma.

Pharmacology: warfarin is highly protein-bound and metabolized primarily by hepatic cytochrome P450 enzymes, notably CYP2C9. Genetic variations in VKORC1 and CYP2C9 contribute to dosing differences. It originated as a rodenticide developed in the mid-20th century; its medical use began in the 1950s, and the name warfarin derives from the Wisconsin Alumni Research Foundation (WARF). Brand names include Coumadin and Jantoven.