Critical
Amiodarone × Warfarin
Class III antiarrhythmics (Vaughan Williams)×Vitamin K antagonist anticoagulants
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.
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: FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers (2024)– FDA Center for Drug Evaluation and Research, last updated 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)