Amiodarone-Warfarin Interaction — EECC MCQ

Correct answer: C — Amiodarone inhibits CYP2C9 and CYP3A4 metabolism of warfarin, increasing warfarin levels by 30-50%; the warfarin dose should be empirically reduced by approximately one-third to one-half when amiodarone is started, with frequent INR monitoring

Amiodarone is a potent inhibitor of CYP2C9 (the primary enzyme metabolising S-warfarin, the more potent enantiomer) and CYP3A4, increasing warfarin plasma levels by 30-50%. This interaction has a slow onset (1-2 weeks, reflecting amiodarone's long loading phase and half-life) and persists for weeks after amiodarone discontinuation (extremely long half-life of ~40-55 days). Practical management: (1) empirically reduce warfarin dose by 30-50% when starting amiodarone; (2) monitor INR at least twice weekly for 4-6 weeks; (3) continue close monitoring after amiodarone dose changes or discontinuation. DOACs cannot be used with mechanical valves (RE-ALIGN contraindication). This is one of the most clinically important drug-drug interactions in cardiology.

Reference: BNF; ESC (2024): AF Guidelines