Drug Interaction Report

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 Clinical and laboratory monitoring should be considered whenever a strong CYP450 3A4 inhibitor is added to or withdrawn from therapy with capmatinib, and the dosage adjusted as necessary based on clinical response and toxicity.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

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 Clinical and laboratory monitoring should be considered whenever a strong CYP450 3A4 inhibitor is added to or withdrawn from therapy with capmatinib, and the dosage adjusted as necessary based on clinical response and toxicity.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

ADJUST DOSING INTERVAL: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.