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What is the warfarin dose adjustment when starting amiodarone in a 68-year-old male with AFib? On warfarin 5mg daily, INR has been 2.4 for 6 months.
Amiodarone is a potent inhibitor of CYP2C9 and CYP3A4 FDA 2024, the primary enzymes responsible for warfarin metabolism. Expect an INR rise within 1–2 weeks.
Recommended approach: Reduce warfarin dose by 30–50% at amiodarone initiation, then check INR every 3–5 days for the first 2 weeks NEJM 2019. Holbrook et al. found that empiric reduction of 35% prevented over-anticoagulation in 78% of patients vs. dose-adjustment after INR rose J Thromb Haemost 2019.
For this patient (warfarin 5mg/d, stable INR), I'd recommend warfarin 3mg daily starting day 1 of amiodarone, with INR check on day 3 and day 7. Re-evaluate weekly until stable. Expect interaction to peak at 4–7 weeks as amiodarone steady-state is reached.
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