Drug Interactions between Crestor and sofosbuvir / velpatasvir

ADJUST DOSE: Coadministration with velpatasvir may significantly increase the plasma concentrations of rosuvastatin. The proposed mechanism is velpatasvir inhibition of the hepatic uptake of rosuvastatin via organic anion transporting polypeptide 1B1 (OATP1B1). Inhibition of breast cancer resistance protein (BCRP)-mediated transport may also contribute. In 18 healthy volunteers, administration of a single 10 mg dose of rosuvastatin with velpatasvir 100 mg once daily increased mean rosuvastatin peak plasma concentration (Cmax) by approximately 2.6-fold and systemic exposure (AUC) by 2.7-fold compared to rosuvastatin administered alone. By contrast, when a single 40 mg dose of pravastatin was given with velpatasvir 100 mg once daily, mean Cmax and AUC of pravastatin increased by just 28% and 35%, 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: Rosuvastatin should not exceed a dosage of 10 mg daily when prescribed with sofosbuvir-velpatasvir. Alternatively, fluvastatin or pravastatin may be substituted, as the former is not a substrate of OATP1B1, and the latter has been found to not interact significantly with velpatasvir. 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.