Drug Interactions between daclatasvir and fluvastatin

MONITOR: Coadministration with daclatasvir may increase the plasma concentrations of drugs that are substrates of the organic anion transporting polypeptide 1B1 (OATP 1B1) or breast cancer resistance protein (BCRP) transporters, such as HMG-CoA reductase inhibitors. The mechanism is decreased clearance due to inhibition of OATP1B1-mediated hepatic uptake and BCRP-mediated intestinal and hepatobiliary efflux by daclatasvir. The interaction has been demonstrated for rosuvastatin, a known substrate of both OATP 1B1 and BCRP. When a single 10 mg dose of rosuvastatin was administered with daclatasvir 60 mg once daily, rosuvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.0- and 1.6-fold, respectively.

MANAGEMENT: Caution and monitoring for adverse effects are advised during concomitant use of daclatasvir with drugs that are substrates of the OATP1B1 or BCRP transporters, particularly HMG-CoA reductase inhibitors. It is advisable to monitor lipid levels and use the lowest effective statin dose. 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.