Major
Atorvastatin × diltiazem
HMG-CoA reductase inhibitors (statins)×Calcium channel blocker, non-DHP (benzothiazepine derivative)
Mechanism
Diltiazem moderately inhibits CYP3A4 – a partial atorvastatin metabolic route. Atorvastatin plasma levels rise 2- to 3-fold. The effect is smaller than with simvastatin (atorvastatin's CYP3A4 dependence is weaker).
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 atorvastatin at 20 mg/day when combined. If LDL targets are missed, switch to pravastatin or rosuvastatin. Alternative to diltiazem: amlodipine or a beta-blocker.