A patient with atrial fibrillation on amiodarone is started on warfarin. The expected interaction and the correct dose adjustment is:

• A Amiodarone induces CYP2C9, reducing warfarin levels; warfarin dose should be increased
• B Amiodarone displaces warfarin from albumin binding, transiently increasing free warfarin; no dose adjustment needed
• C Amiodarone inhibits vitamin K epoxide reductase directly, synergistically increasing anticoagulation
• D Amiodarone inhibits CYP2C9 (primary warfarin S-enantiomer metabolism) and CYP3A4, approximately doubling warfarin levels; warfarin dose should be reduced by 30–50% and INR monitored closely ✓

Explanation

Amiodarone and its active metabolite desethylamiodarone are potent inhibitors of CYP2C9 (which metabolises the more pharmacologically active S-warfarin enantiomer) and CYP3A4. This inhibition reduces warfarin clearance significantly, potentially doubling its plasma levels and causing dangerous supratherapeutic INR elevation. Because amiodarone has an extremely long half-life (40–55 days), this interaction persists for months after amiodarone discontinuation. Clinical guidelines recommend reducing warfarin dose by 30–50% when amiodarone is co-prescribed and monitoring INR weekly for the first month, then monthly.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.