Drug Interactions between amprenavir and Crestor

ADJUST DOSE: Coadministration with protease inhibitors may significantly increase the plasma concentrations of rosuvastatin. The mechanism may involve inhibition of OATP1B1-mediated hepatic uptake and/or BCRP-mediated intestinal and hepatobiliary efflux. In 15 healthy volunteers, administration of rosuvastatin 20 mg once a day with lopinavir-ritonavir 400 mg-100 mg twice a day for 7 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) compared to administration of rosuvastatin alone. One subject had asymptomatic creatine phosphokinase elevation 17 times the upper limit of normal (ULN) and another had liver function test elevation between 1.1 and 2.5 times ULN. In a study with 11 subjects, administration of rosuvastatin 5 mg once daily in combination with once daily morning doses of ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg) plus twice daily doses of dasabuvir resulted in increases of rosuvastatin Cmax and AUC by approximately 7.1- and 2.6-fold, respectively. Likewise, atazanavir/ritonavir 300 mg/100 mg given once daily for 8 days increased the Cmax and AUC of a single 10 mg dose of rosuvastatin by 7.0- and 3.1-fold, respectively. 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 using rosuvastatin with protease inhibitors should be carefully weighed against the potentially increased risk of myopathy including rhabdomyolysis. If coadministration is required, rosuvastatin should be initiated at the lowest effective dosage and not exceed 10 mg per day when prescribed with lopinavir-ritonavir, atazanavir-ritonavir, atazanavir-cobicistat, or ombitasvir/paritaprevir/ritonavir plus dasabuvir. The dosage of rosuvastatin should be limited to 20 mg once a day when used with darunavir-cobicistat. Nirmatrelvir-ritonavir product labeling advises temporary discontinuation of rosuvastatin be considered during treatment with nirmatrelvir-ritonavir. Alternatively, a different HMG-CoA reductase inhibitor such as fluvastatin may be considered. 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.