Simultaneous Use of Amiodarone Influences Warfarin Maintenance Dose but Is Not Associated with Adverse Events

BACKGROUND: Drug interaction studies selecting patients in a real-life setting are scarce, and most studies to date are characterized by a small sample size. OBJECTIVE: To evaluate the effect of amiodarone on warfarin maintenance dose and adverse events in an anticoagulation cohort from a tertiary cardiovascular service. METHODS: This study recruited 866 patients, and oral anticoagulant therapy was monitored by the prothrombin time expressed as the international normalized ratio (INR). Genotyping of CYP2C9*2, CYP2C9*3, and VKORC1 3673 polymorphisms was performed. RESULTS: Of the 866 patients, 111 (12.8%) were taking amiodarone and warfarin simultaneously, and 514 (59.4%) reached the therapeutic target dose. The warfarin maintenance dose was significantly lower in patients simultaneously using amiodarone (23.8 ± 11.3 mg/wk) compared with other patients (29.5 ± 14.3 mg/wk; P < 0.001). Patients taking amiodarone had higher INR/current dose ratios (0.83 ± 0.04 per mg) compared with patients not using amiodarone (0.71 ± 0.02 per mg, P = 0.001). Adverse event frequency was not different between the groups (P = 0.40). No genotype effect was noted on the odds of bleeding associated with amiodarone use. CONCLUSIONS: Simultaneous use of amiodarone influences warfarin maintenance dose, but is not associated with adverse events.