Drug Interaction Report

ADJUST DOSE: Coadministration with capmatinib may increase the plasma concentrations of rosuvastatin. The proposed mechanism is inhibition of breast cancer resistance protein (BCRP) efflux transporter in the gut wall by capmatinib, resulting in increased absorption and bioavailability of rosuvastatin. In adult patients with mesenchymal-epithelial transition (MET)-dysregulated advanced solid tumors, administration of a single 10 mg dose of rosuvastatin following treatment with capmatinib 400 mg twice daily for 12 days increased mean rosuvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) by 204% and 108%, respectively, but had no significant effect on rosuvastatin elimination half-life. 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 dosage of rosuvastatin should start at 5 mg and not exceed 10 mg once daily (some authorities suggest 20 mg once daily based on the reported magnitude of interaction) when used in combination with capmatinib. Alternatively, a different statin that is not expected to be significantly affected by BCRP inhibition such as pitavastatin or pravastatin 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.