The incidence, magnitude, and time course of the amiodarone-warfarin interaction

Eight patients concurrently treated with amiodarone and warfarin sodium were studied to characterize the interaction between these drugs. All fulfilled the following criteria: (1) stable and therapeutic prothrombin time (PT) at baseline, defined as at least two consecutive PTs obtained within two weeks before beginning amiodarone therapy that varied by less than or equal to 15%; (2) no warfarin dosage adjustment in the two weeks prior to amiodarone therapy; (3) no other drugs given that alter coagulation study results; and (4) follow-up PTs obtained 1, 2, 4, and 8 weeks after initiation of amiodarone treatment. A clinically significant change in PT was defined as greater than 15%. Mean baseline PT was 19.8 s for patients receiving 5.99 mg/d of warfarin sodium. Patients had a mean maximum increase in PT of 44% (range, 22% to 108%), which occurred during the first two weeks. In six patients, the PT returned to within 15% of baseline by week 4 or 8, and the daily warfarin requirement had decreased by 35% (range, 25% to 50%). Two patients had PTs varying by greater than 15% from baseline at week 8 despite a 33% reduction in warfarin dosage in each case. No patient in this series encountered complications of anticoagulant therapy, perhaps due to early recognition and dosage reduction. Although the mechanism remains unclear, our study indicates that amiodarone potentiation of warfarin effects occurs in all patients, occurs in the first two weeks of amiodarone therapy, variably increases PT by 22% to 108%, and lowers the warfarin requirement by 25% to 50%. We recommend a 25% prophylactic reduction of warfarin dosage and weekly measurements of PT for one month when amiodarone therapy is initiated.