Drug Interactions between Plavix and rosuvastatin

ADJUST DOSE: Coadministration with clopidogrel may increase the plasma concentrations of drugs that are substrates of the breast cancer resistance protein (BCRP) such as rosuvastatin. The proposed mechanism is decreased rosuvastatin clearance due to inhibition of BCRP-mediated intestinal and hepatic transport by clopidogrel and its metabolite. In 20 patients with stable coronary artery disease, administration of rosuvastatin 40 mg daily with a 300 mg loading dose of clopidogrel increased rosuvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.3- and 2.0-fold, respectively. Following continued administration of rosuvastatin with clopidogrel 75 mg daily for 7 days, rosuvastatin AUC was increased by 1.4-fold while Cmax was not significantly altered. High levels of HMG-CoA reductase inhibitory activity in plasma are 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. Isolated cases of suspected rosuvastatin-induced hepatotoxicity have also been reported in patients concomitantly treated with clopidogrel.

MANAGEMENT: When concomitant use of clopidogrel is required, the lowest possible starting dosage or a reduction of the existing dosage of rosuvastatin should be considered. Some authorities recommend not exceeding 20 mg/day of rosuvastatin when prescribed with clopidogrel. Alternatively, a different HMG-CoA reductase inhibitor that is not a substrate for BCRP (e.g., fluvastatin, pitavastatin, pravastatin, simvastatin) may be considered. 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.