Gemfibrozil × Rosuvastatin

Rosuvastatin is an OATP1B1 substrate and gemfibrozil blocks that transporter. Statin exposure rises, and with it the risk of myopathy and rhabdomyolysis, as with other HMG-CoA reductase inhibitors.

Muscle pain and weakness, muscle tenderness, darkening urine, rising creatine kinase. Rhabdomyolysis brings acute renal failure with it.

Spanish SmPCs for gemfibrozil and rosuvastatin contraindicate gemfibrozil with rosuvastatin 40 mg. At lower doses the combination is not recommended either: the gemfibrozil SmPC requires avoiding gemfibrozil with any statin and allows only low rosuvastatin doses when the benefit outweighs the risk, and the rosuvastatin SmPC does not recommend the combination. If it cannot be avoided, rosuvastatin is started at 5 mg once daily (rosuvastatin SmPC). The US Food and Drug Administration (FDA) labels of both drugs cap rosuvastatin at 10 mg once daily. Ask the patient to report unexplained muscle pain, weakness or cramps promptly. Check creatine kinase if they occur, and stop treatment if it is more than 5 times the upper limit of normal (gemfibrozil and rosuvastatin SmPCs). Myopathy and rhabdomyolysis have occurred as early as 3 weeks and as late as several months into combined use, and routine creatine kinase checks do not guarantee that severe muscle and kidney damage will be prevented (gemfibrozil FDA label).