Drug Interaction Report

GENERALLY AVOID: Coadministration with capmatinib may increase the plasma concentrations and risk of adverse effects of drugs that are substrates of P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) transporters, such as digoxin and rosuvastatin. The proposed mechanism is decreased clearance due to capmatinib-mediated inhibition of intestinal P-gp and/or BCRP efflux transport proteins. Coadministration with capmatinib increased the systemic exposure (AUC0-INF) and peak plasma concentration (Cmax) of digoxin (a P-gp substrate) by 47% and 74%, respectively. Concomitant use of capmatinib increased the AUC0-INF and Cmax of rosuvastatin (a BCRP substrate) by 108% and 204%, respectively.

MANAGEMENT: Coadministration of capmatinib with drugs that are substrates of P-gp and/or BCRP should generally be avoided. However, if concomitant use is unavoidable, caution is advised, particularly with drugs that have a narrow therapeutic range. Clinical and laboratory monitoring should be considered whenever capmatinib is added to or withdrawn from therapy with these drugs, and dosages adjusted as necessary. Patients should be monitored for the development of adverse effects.

ADJUST DOSING INTERVAL: Consumption of food can decrease the rate and extent of gastrointestinal absorption of sirolimus. Also, the consumption of grapefruit juice may result in increased sirolimus trough concentrations.

MANAGEMENT: Experts recommend that this drug be taken either at least one hour prior to eating or consistently with or without food to avoid variations in sirolimus blood levels. The manufacturer recommends against using grapefruit juice for dilution of sirolimus doses. Patients should be monitored for clinical and laboratory evidence of altered immunosuppressant effects.