Drug Interactions between atorvastatin and sofosbuvir / velpatasvir

MONITOR: Coadministration with velpatasvir may increase the plasma concentrations of the HMG-CoA reductase inhibitors atorvastatin and simvastatin. The proposed mechanism has not been delineated but may involve velpatasvir inhibition of the hepatic uptake transporter organic anion transporting polypeptide 1B (OATP1B), and the efflux transporters P-glycoprotein (P-gp), and/or breast cancer resistance protein (BCRP), of which atorvastatin and simvastatin are substrates. The interaction has not been studied specifically with all statins; data are currently available for rosuvastatin. 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: The lowest dose of atorvastatin or simvastatin should be used when prescribed with sofosbuvir-velpatasvir, and the dosage titrated cautiously. Pravastatin may be considered as a substitute. 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.