Drug Interactions between Crixivan and rosuvastatin

ADJUST DOSE: Coadministration with protease inhibitors such as indinavir may significantly increase the plasma concentrations of rosuvastatin. The mechanism of interaction has not been described. Data are available for lopinavir-ritonavir only. In healthy volunteers, administration of rosuvastatin (20 mg once a day for 7 days) in combination with lopinavir-ritonavir (400 mg-100 mg twice a day for 10 days) was associated with an approximately 5-fold increase in rosuvastatin steady-state peak plasma concentration (Cmax) and a 2-fold increase in systemic exposure (AUC). This interaction is considered clinically significant. 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.

MANAGEMENT: Rosuvastatin may be used with caution and close monitoring in patients treated with indinavir, although the lowest possible dosage should be used. Fluvastatin, pitavastatin, and pravastatin may be safer alternatives, since they are not metabolized by CYP450 3A4. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.