invirase and Crestor Interactions

Interactions between invirase(saquinavir) and Crestor (rosuvastatin)

saquinavir and rosuvastatin (Major Drug-Drug)

ADJUST DOSE: Coadministration with protease inhibitors 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: The benefits of lipid lowering with rosuvastatin in HIV patients receiving protease inhibitors should be carefully weighed against the potential risks of increased systemic exposure to rosuvastatin. If the combination is prescribed, the lowest dosage of rosuvastatin should be used and close monitoring for musculoskeletal toxicity is recommended. The dosage of rosuvastatin should be limited to 10 mg once a day when used in combination with lopinavir-ritonavir. Alternatively, a different HMG-CoA reductase inhibitor such as fluvastatin or pravastatin may be considered. All patients treated with HMG-CoA reductase inhibitors 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.