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 Clinical and laboratory monitoring should be considered whenever capmatinib is added to or withdrawn from therapy with these drugs, and dosages adjusted as necessary.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.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pazopanib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Although not studied, the interaction may increase the risk of QT interval prolongation and torsade de pointes arrhythmia as well as severe and fatal hepatotoxicity associated with the use of pazopanib.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of pazopanib. The mechanism of interaction is unknown. Administration of pazopanib with a high-fat or low-fat meal results in an approximately 2-fold increase in peak plasma concentration (Cmax) and systemic exposure (AUC).

MANAGEMENT: Patients treated with pazopanib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Pazopanib should be administered at least one hour before or two hours after a meal.