Drug Interactions between fluvastatin and fostemsavir

ADJUST DOSE: Coadministration with fostemsavir may increase the plasma concentrations of most HMG-CoA reductase inhibitors (i.e., statins) to varying degrees. The proposed mechanism is inhibition of organic anion transporting polypeptide (OATP) 1B1/1B3-mediated hepatic uptake by temsavir, the active moiety of fostemsavir. Inhibition of breast cancer resistance protein (BCRP)-mediated intestinal and hepatic transport of statins may also contribute. When a single 10 mg dose of rosuvastatin was administered with fostemsavir 600 mg twice daily in 18 study subjects, mean rosuvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 78% and 69%, respectively, compared to rosuvastatin administered alone. High levels of HMG-CoA reductase inhibitory activity in plasma may be 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 effective dosage of a statin should be used when prescribed with fostemsavir, and the dosage titrated cautiously based on clinical response and adverse events. Alternatively, pravastatin may be considered as it is not a substrate of BCRP and therefore, not expected to interact significantly with fostemsavir. 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.