Drug Interactions between Crestor and gemfibrozil

GENERALLY AVOID: Coadministration with gemfibrozil may significantly increase the plasma concentrations of rosuvastatin. The proposed mechanism is gemfibrozil inhibition of the hepatic uptake of rosuvastatin via organic anion transporting polypeptide 2 (OATP-2). In 20 healthy volunteers, gemfibrozil (600 mg twice a day for 7 days) increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of rosuvastatin (80 mg single oral dose) by 120% and 90%, respectively, compared to placebo. 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. Although there was no evidence of increased skeletal muscle effects when rosuvastatin was used with fibric acid derivatives including gemfibrozil in clinical trials, an increase in the incidence of myositis and myopathy has been observed in patients receiving other HMG-CoA reductase inhibitors with fibric acid derivatives.

MANAGEMENT: Concurrent use of rosuvastatin and gemfibrozil should generally be avoided unless the benefit of further alterations in lipid levels is anticipated to outweigh the potential risks. Addition of fibrates to HMG-CoA reductase inhibitor therapy typically provides little additional reduction in LDL cholesterol, but further reductions of triglycerides and increases in HDL cholesterol may be attained. The daily dosage of rosuvastatin should not exceed 10 mg when used in combination with gemfibrozil. Patients should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.