Major
Amlodipine × Simvastatin
Calcium channel blockers (dihydropyridines)×HMG-CoA reductase inhibitors (statins)
Mechanism
Amlodipine moderately inhibits CYP3A4 – the main simvastatin metabolic route. Simvastatin plasma levels rise by about 77%. Rhabdomyolysis has been reported at simvastatin doses of 40 mg or above.
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 20 mg/day when combined with amlodipine. If LDL targets are missed, switch to pravastatin or rosuvastatin (no CYP3A4 dependence) or replace amlodipine with lisinopril or telmisartan.
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
- FDA: Zocor (simvastatin) prescribing information (2012)