CriticalClass III antiarrhythmics (Vaughan Williams)×Vitamin K antagonist anticoagulants
Updated · Methodology
Mechanism
Warfarin acts via two stereoisomers: S-warfarin (5-fold more active) and R-warfarin. Amiodarone strongly inhibits CYP2C9 (the S-warfarin pathway) and, to a lesser extent, CYP3A4 (the R-warfarin pathway). The active form accumulates; the international normalised ratio (INR, a marker of blood clotting) rises 2- to 4-fold. The effect develops slowly over 1–7 weeks because amiodarone has a very long half-life.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal and intracranial haemorrhage with fatal outcomes – reported at INR above 10.
Management
The combination is acceptable when amiodarone cannot be replaced by another antiarrhythmic. Reduce warfarin dose empirically by 30–50% at the time amiodarone is added. Check INR every 3–5 days for the first month, then every 2 weeks. The interaction persists for several weeks after amiodarone is stopped – return warfarin to baseline dose gradually.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Sources
- Lexicomp: Lexicomp Drug Interactions (2024)– Wolters Kluwer Clinical Drug Information, Inc. Lexi-Interact Online, 2024
- Pharmaceutical Press: Stockley's Drug Interactions, 12th edition (2024)– Preston CL (ed.). Stockley's Drug Interactions. 12th ed. London: Pharmaceutical Press; 2024
- FDA: Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers (2024)– FDA, Clinical Drug Interaction Studies, table of CYP substrates, inhibitors and inducers, 2024
- AEMPS: Ficha técnica de Warfarina – interacciones con amiodarona (2024)– AEMPS CIMA. Ficha técnica de warfarina, sección 4.5 (interacciones medicamentosas con amiodarona). Madrid: Agencia Española de Medicamentos y Productos Sanitarios.
- ACC/AHA: 2014 AHA/ACC/HRS Guideline for AF Management (2014)