Moderate
Established
Deskripsi
Amlodipine inhibits CYP3A4-mediated simvastatin metabolism, increasing simvastatin plasma concentrations and the risk of statin-associated myopathy and rhabdomyolysis.
Mekanisme
Simvastatin acid is primarily metabolised by CYP3A4; amlodipine is a weak-to-moderate CYP3A4 inhibitor that reduces simvastatin clearance, increasing systemic exposure.
Signifikansi Klinis
FDA has limited the maximum simvastatin dose to 20 mg/day when combined with amlodipine to reduce myopathy and rhabdomyolysis risk.
Penatalaksanaan
Do not exceed simvastatin 20 mg/day when co-administered with amlodipine; consider switching to a statin not dependent on CYP3A4 (pravastatin, rosuvastatin) if higher statin intensity is needed.