An Evaluation of the Early Pharmacodynamic Response After Simultaneous Initiation of Warfarin and Amiodarone

Amiodarone inhibits the metabolism of warfarin. Previous studies characterizing this drug interaction have focused on the effect of adding amiodarone to stable doses of warfarin. The objective of this study was to assess whether simultaneous initiation of warfarin and amiodarone results in early alteration of the international normalized ratio (INR) response to warfarin. Patients initiated on warfarin and amiodarone during the same hospitalization were included in the amiodarone (AMIO) group. Patients initiated on warfarin alone (n = 42) were identified for the CONTROL group. The AMIO and CONTROL groups were matched based on age, gender, and ejection fraction <40% using propensity score matching (final n = 18 patients per group). Total and average daily warfarin dose was lower in the AMIO group, yet INR values were similar on each day between the 2 groups. More patients in the AMIO group had an INR greater than 2 during the 5-day observation period as compared to the CONTROL group. In addition, there were trends toward greater deviation from INR values expected with a 5-mg daily warfarin dose among AMIO group patients. Simultaneous initiation of warfarin and amiodarone leads to an enhanced pharmacodynamic response to warfarin early in therapy. Although these data should be viewed as hypothesis generating, cautious dosing and monitoring with simultaneous initiation of warfarin and amiodarone may be warranted.