Drug Interactions between capmatinib and emtricitabine / nelfinavir / tenofovir disoproxil

MONITOR CLOSELY: Coadministration of capmatinib with strong 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.

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 Clinical and laboratory monitoring should be considered whenever a strong CYP450 3A4 inhibitor is added to or withdrawn from therapy with capmatinib, and the dosage adjusted as necessary based on clinical response and toxicity.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

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 Clinical and laboratory monitoring should be considered whenever capmatinib is added to or withdrawn from therapy with these drugs, and dosages adjusted as necessary.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