Clinical observations with the amiodarone/warfarin interaction - Dosing relationships with long-term therapy

Objectives: The interaction between amiodarone and warfarin has only been described in patients being followed up for relatively short time periods. The objectives of this study were to characterize the interaction between these two agents in a clinical situation over a longer period of time in a larger cohort of patients, and to determine the relationship between the maintenance dose of amiodarone and the resultant need to adjust the dose of warfarin. Design: This was an observational trial of a cohort of patients receiving a stable warfarin regimen in whom oral amiodarone was initiated. Patients received both amiodarone and warfarin for at least I year, and the dosage of warfarin was adjusted as clinically necessary to achieve an international nomalized ratio of 2 to 3. Data from a total of 43 patients were analyzed. Results: At baseline, prior to initiation of amiodarone, the warfarin dose was 5.2 +/- 2.6 mg/d. The magnitude of the interaction between these two agents peaked at 7 weeks, which resulted in a 44% mean maximum reduction in the warfarin dose. The warfarin dose inversely correlated with the maintenance dose of amiodarone (r(2) = 0.94, p < 0.005). Minor bleeding episodes occurred in five patients (12%). For patients receiving amiodarone maintenance doses of 400, 300, 200, or 100 mg/d, it is recommended that the daily warfarin dose be reduced by approximately 40%, 35%, 30%, or 25%, respectively. Conclusions: The magnitude of the amiodarone/warfarin interaction is highly dependent on the maintenance dose of amiodarone. This relationship can aid clinicians in adjusting the dose of warfarin patients receiving long-term arniodarone treatment.