A 58-year-old man with atrial fibrillation on warfarin (INR 2.5) is started on amiodarone for rate control. Which of the following is the most appropriate management to prevent warfarin toxicity?

Explanation

## Drug Interaction: Warfarin and Amiodarone **Key Point:** Amiodarone is a potent inhibitor of CYP3A4 and CYP2C9, significantly increasing warfarin levels and INR. Dose reduction is mandatory. ### Mechanism of Interaction 1. Amiodarone inhibits hepatic metabolism of warfarin (especially the active S-enantiomer via CYP2C9). 2. This prolongs warfarin's half-life from ~36 hours to >100 hours. 3. INR rises within 3–5 days, peaking at 7–14 days. ### Management Strategy | Step | Action | Rationale | |------|--------|----------| | **Baseline** | Document current INR (2.5 here) | Establish reference | | **Initiate amiodarone** | Reduce warfarin dose by 30–50% | Prevent supratherapeutic INR | | **Monitor** | Check INR at 3–5 days, then weekly × 2–4 weeks | Detect peak interaction early | | **Adjust** | Titrate warfarin to target INR 2–3 | Maintain therapeutic anticoagulation | **High-Yield:** The interaction is **bidirectional**: warfarin also increases amiodarone levels slightly, but the warfarin elevation is clinically more significant. **Clinical Pearl:** Even a modest amiodarone dose (200 mg/day) causes a clinically relevant interaction. Patients on this combination require closer INR monitoring than those on warfarin alone. **Warning:** Do NOT increase warfarin dose — this will cause over-anticoagulation and bleeding risk once amiodarone effect plateaus.