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 Clinical and laboratory monitoring should be considered whenever capmatinib is added to or withdrawn from therapy with these drugs, and dosages adjusted as necessary.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: Food may reduce the oral bioavailability of silodosin. The effect of a moderate-fat, moderate-calorie meal on silodosin pharmacokinetics was variable and decreased silodosin maximum plasma concentration (Cmax) by approximately 18% to 43% and systemic exposure (AUC) by 4% to 49% across three different studies. The maximum effect of food (i.e., coadministration with a high-fat, high-calorie meal) on the pharmacokinetics of silodosin was not evaluated. Safety and efficacy clinical trials for silodosin were always conducted in the presence of food intake.

MANAGEMENT: Patients should be instructed to take silodosin with a meal to reduce the risk of adverse events.