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 Clinical and laboratory monitoring should be considered whenever capmatinib is added to or withdrawn from therapy with these drugs, and the dosages adjusted as necessary.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: Food may reduce the rate and extent of absorption of methylnaltrexone following oral administration. When a single 450 mg oral dose of methylnaltrexone was administered with a high-fat breakfast (approximately 800 to 1000 calories; 60% from fat, 25% from carbohydrate, and 15% from protein) in healthy study subjects, methylnaltrexone peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 60% and 43%, respectively, while time to reach Cmax delayed by 2 hours.

MANAGEMENT: Oral methylnaltrexone should be taken with water on an empty stomach at least 30 minutes before the first meal of the day.