Atorvastatin × Diltiazem

CYP3A4 takes part in atorvastatin metabolism (atorvastatin labels), and diltiazem is a moderate CYP3A4 inhibitor (diltiazem and atorvastatin labels). With diltiazem 240 mg daily, atorvastatin AUC rose 1.51-fold (atorvastatin labels in Spain and the US). The risk of muscle damage, up to rhabdomyolysis, rises with statin exposure (diltiazem labels). The effect is stronger with simvastatin, whose AUC diltiazem raised 5-fold (diltiazem labels).

Muscle pain, cramps or weakness, especially with fever and malaise, and raised creatine kinase. In severe cases rhabdomyolysis develops: creatine kinase above 10 times the upper limit of normal, myoglobin in blood and urine (dark urine) and possible kidney failure (atorvastatin label).

When possible, combine diltiazem with a statin that is not metabolized by CYP3A4 (diltiazem labels in Spain and the US). Pravastatin is an example: diltiazem did not change its pharmacokinetics (diltiazem labels). If atorvastatin is kept, start it at the lowest effective dose (diltiazem label) and consider a lower maximum dose (atorvastatin label); the FDA diltiazem label also allows dose adjustment of both drugs. Monitor the patient closely after diltiazem is started and after each dose change (atorvastatin and diltiazem labels). Ask the patient to report muscle pain, cramps or weakness at once. If they appear, measure creatine kinase and stop atorvastatin if it is above 5 times the upper limit of normal (atorvastatin label).