Moderate
Atorvastatin × Simvastatin
HMG-CoA reductase inhibitors (statins)×HMG-CoA reductase inhibitors (statins)
Mechanism
Dual statin therapy – additive myopathy and rhabdomyolysis risk. Simvastatin additionally depends on CYP3A4 (by 98%), amplifying risk.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Symptoms usually appear 2–6 weeks after starting the combination.
Management
The combination is not prescribed. Use one statin titrated to LDL target. If insufficient, add ezetimibe.