warfarinu

Warfarin is an oral anticoagulant used to prevent and treat thromboembolic disorders. It works by inhibiting vitamin K epoxide reductase, which reduces the synthesis of vitamin K–dependent clotting factors II, VII, IX, and X, as well as proteins C and S. Warfarin is a racemic mixture of R- and S-enantiomers, with S-warfarin being more potent and primarily metabolized by CYP2C9 in the liver. The anticoagulant effect develops gradually over several days.

Common indications include prevention of stroke in nonvalvular atrial fibrillation, treatment and prevention of deep vein thrombosis and pulmonary embolism, and management of patients with mechanical heart valves. It is often used for long-term management and may require bridging with heparin around procedures.

Dosing is individualized based on the target INR, typically 2.0–3.0 for many conditions; mechanical heart valves may require a slightly higher target such as 2.5–3.5. Initial doses around 5 mg daily are common, but adjustments are made based on INR measurements. INR is monitored regularly (daily or weekly after initiation, then every 4–12 weeks once stable). The onset of full effect takes several days, and dose changes may take several days to reflect in INR.

Diet and drug interactions are important. Vitamin K intake should be kept consistent, as large fluctuations can alter anticoagulation. Many drugs affect warfarin activity, including certain antibiotics, antifungals, amiodarone, rifampin, and NSAIDs, which can increase or decrease bleeding risk.

Adverse effects include major bleeding and, less commonly, skin necrosis and purple toe syndrome. Warfarin is teratogenic and generally avoided in pregnancy; alternatives may be used in pregnant patients. Reversal in case of serious bleeding or urgent procedures is achieved with vitamin K, and sometimes fresh frozen plasma or prothrombin complex concentrates.