Drug Interaction Report

GENERALLY AVOID: Coadministration with capmatinib may increase the plasma concentrations and risk of adverse effects of drugs that are substrates of multidrug and toxin extrusion 1 and 2K (MATE1 and MATE2K) proteins, such as methylnaltrexone and tipiracil. The proposed mechanism is decreased clearance due to capmatinib-mediated inhibition of MATE1 and/or MATE2K.

MANAGEMENT: Coadministration of capmatinib with drugs that are substrates of MATE1 and/or MATE2K 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 Clinical and laboratory monitoring should be considered whenever capmatinib is added to or withdrawn from therapy with these drugs, and the dosages adjusted as necessary. Patients should be monitored for the development of adverse effects.

ADJUST DOSING INTERVAL: Administration of trifluridine-tipiracil with a standardized high-fat, high-calorie meal has been shown to decrease trifluridine peak plasma concentration (Cmax) as well as tipiracil Cmax and systemic exposure (AUC) by approximately 40% compared to administration in a fasting state in patients with cancer given a single 35 mg/m2 dose. No change in trifluridine AUC was observed.

MANAGEMENT: Based on the observed correlation between increases in the Cmax of trifluridine and decreases in neutrophil counts, trifluridine-tipiracil should be taken within one hour after completion of the morning and evening meals.