Major
Simvastatin × Verapamil
HMG-CoA reductase inhibitors (statins)×Non-dihydropyridine calcium channel blocker
Mechanism
Verapamil moderately inhibits CYP3A4 – the main simvastatin metabolic route. Simvastatin plasma levels rise 2- to 4-fold. FDA Zocor caps simvastatin at 10 mg/day with verapamil.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
Cap simvastatin at 10 mg/day when combined. If LDL targets are missed, switch to pravastatin or rosuvastatin (no CYP3A4 dependence) or replace verapamil with a beta-blocker/diuretic.