Drug Interaction Report

MONITOR: Coadministration of capmatinib with moderate CYP450 3A4 inhibitors may increase the risk and severity of capmatinib adverse effects, such as interstitial lung disease, pneumonitis, and hepatotoxicity. The proposed mechanism is decreased clearance due to inhibition of CYP450 3A4, which is one of the primary enzymes responsible for the metabolic clearance of capmatinib. Coadministration with itraconazole (a strong CYP450 3A4 inhibitor) increased the systemic exposure (AUC) of capmatinib by 42%, but did not affect the peak plasma concentration (Cmax) of capmatinib. Data are not available for other, less potent inhibitors.

MANAGEMENT: Close monitoring is recommended whenever capmatinib is used with a moderate CYP450 3A4 inhibitor. Clinical and laboratory monitoring should be considered whenever a moderate CYP450 3A4 inhibitor is added to or withdrawn from therapy with capmatinib, and the dosage adjusted as necessary based on clinical response and toxicity. Patients should be monitored for the development of adverse effects.