ticagrelor and simvastatin

Ticagrelor is a mild inhibitor of cytochrome P450 3A4 (CYP3A4). Simvastatin is primarily metabolised by CYP3A4. Inhibition of CYP3A4 by ticagrelor reduces the metabolic clearance of simvastatin and its active metabolites, leading to increased systemic exposure.

Elevated simvastatin concentrations increase the risk of dose-related adverse effects, particularly myopathy and rhabdomyolysis. Patients may present with unexplained muscle pain, tenderness, or weakness, and in severe cases, dark urine and acute kidney injury.

Avoid concomitant use, or if deemed necessary, limit the simvastatin dose to a maximum of 40 mg daily. Alternatively, consider a statin that is not extensively metabolised by CYP3A4, such as pravastatin or rosuvastatin. Monitor patients for symptoms of myopathy and check creatine kinase levels if symptoms develop.

Well established. The interaction is described in the prescribing information for both drugs and supported by pharmacokinetic studies demonstrating increased simvastatin AUC and Cmax when co-administered with ticagrelor.