Critical
Amiodarone × Simvastatin
Class III antiarrhythmics (Vaughan Williams)×HMG-CoA reductase inhibitors (statins)
Mechanism
Amiodarone inhibits CYP3A4 and P-glycoprotein. Simvastatin concentration rises 2–4 fold with risk of rhabdomyolysis and acute kidney injury. FDA Zocor Section 4.3 caps simvastatin at 20 mg/day with amiodarone; above 20 mg – strict contraindication.
Symptoms
Myalgia, weakness, dark urine within 1–4 weeks. CK above 10× ULN.
Management
Cap simvastatin at 20 mg/day. Better option: switch to pravastatin or rosuvastatin (not metabolised via CYP3A4).
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.
Sources
- Lexicomp: Lexicomp Drug Interactions (2024)– Wolters Kluwer Clinical Drug Information, Inc. Lexi-Interact Online, 2024
- FDA: Zocor (simvastatin) prescribing information (2012)