Drug interactions between Crestor and Sandimmune

ADJUST DOSE: Coadministration with cyclosporine may significantly increase the plasma concentrations of rosuvastatin. The proposed mechanism is cyclosporine inhibition of the hepatic uptake of rosuvastatin via organic anion transporting polypeptide C (OATP-C). In 10 stable heart transplant patients receiving an antirejection regimen containing cyclosporine, mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of rosuvastatin (10 mg once daily for 10 days) were increased 11-fold and 7-fold, respectively, compared with historical data from 21 healthy volunteers. High levels of HMG-CoA reductase inhibitory activity in plasma is 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. Rosuvastatin did not affect the plasma concentrations of cyclosporine.

MANAGEMENT: The daily dosage of rosuvastatin should not exceed 5 mg when used in combination with cyclosporine. 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.