Major
amiodarone × simvastatin
Class III antiarrhythmics (Vaughan Williams)×HMG-CoA reductase inhibitors (statins)
Mechanism
Amiodarone inhibits CYP3A4, the enzyme responsible for simvastatin metabolism. Active simvastatin acid concentrations rise 2–3-fold, and the risk of myopathy and rhabdomyolysis increases proportionally. The FDA caps simvastatin at 20 mg/day when used with amiodarone.
Management
Do not exceed 20 mg simvastatin per day. If intolerance occurs or more intensive lipid lowering is needed, switch to pravastatin, fluvastatin, or rosuvastatin (not metabolized by CYP3A4), or use moderate-dose atorvastatin with caution.
Sources
- Lexicomp: Lexicomp Drug Interactions (2024)— Wolters Kluwer Clinical Drug Information, Inc. Lexi-Interact Online, 2024
- FDA: FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury (2011)— FDA Drug Safety Communication, June 8, 2011