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Amiodarone-Warfarin Interaction — RACP Adult Medicine MCQ

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ModerateCardiologyAmiodarone-Warfarin InteractionRACP Adult Medicine

A 45-year-old man is commenced on warfarin for DVT. He is also taking amiodarone, which was started 2 weeks ago. After 3 days of warfarin, his INR is 5.5 (target 2.0–3.0). What is the most likely drug interaction mechanism?

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Correct answer: C — CYP2C9 inhibition decreasing warfarin metabolism

Amiodarone inhibits CYP2C9 (and CYP3A4), the primary enzymes metabolising the S-enantiomer (more potent form) of warfarin. This markedly reduces warfarin metabolism causing supratherapeutic INR. When starting amiodarone with warfarin, the warfarin dose should be empirically reduced by 30–50% with frequent INR monitoring.

Reference: AMH – 2025 – Drug Interactions; eTG Cardiovascular 2024