Drug Interactions between Crestor and dronedarone

MONITOR: Coadministration with dronedarone may increase the plasma concentrations of drugs that are substrates of organic anion transporting polypeptide 1B1 (OATP1B1) such as rosuvastatin. In vitro data indicate that one of dronedarone's metabolites, SR90154, is likely to inhibit OATP1B1 and OATP1B3 in vivo, which may lead to decreased hepatic uptake of rosuvastatin from plasma. Administration of a single 10 mg dose of rosuvastatin during treatment with dronedarone 400 mg every 12 hours increased rosuvastatin systemic exposure (AUC) by 1.4-fold compared to administration of rosuvastatin alone. High levels of HMG-CoA reductase inhibitory activity in plasma may be associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

MANAGEMENT: Dosage adjustments as well as clinical and laboratory monitoring may be appropriate when dronedarone is added to or withdrawn from therapy in patients receiving rosuvastatin. Some authorities recommend not exceeding 20 mg/day of rosuvastatin when prescribed with dronedarone. Patients should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Rosuvastatin should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.