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 Clinical and laboratory monitoring should be considered whenever a moderate CYP450 3A4 inhibitor is added to or withdrawn from therapy with capmatinib, and the dosage adjusted as necessary based on clinical response and toxicity.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

GENERALLY AVOID: Taking stiripentol on an empty stomach may reduce its oral bioavailability. Stiripentol degrades rapidly when exposed to gastric acid in an empty stomach.

GENERALLY AVOID: Alcohol may potentiate the depressant effects of stiripentol on the central nervous system. Concomitant use may result in increased sedation and dizziness as well as impairment of psychomotor skills.

GENERALLY AVOID: It is not known whether stiripentol may reduce theophylline and caffeine metabolism, as data on the potential for inhibition of CYP450 1A2 are limited. Consumption of foods and nutritional products such as cola drinks (which contain significant quantities of caffeine) and chocolate (which contains caffeine and trace amounts of theophylline) may be unsafe during treatment with stiripentol, particularly in children.

MANAGEMENT: Stiripentol should be taken during a meal for optimal absorption; however, it should not be taken with milk, dairy products (e.g., yogurt, soft cream cheese), fruit juice, or carbonated beverages. Patients should be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them. Food and beverages that may contain caffeine or theophylline such as colas, chocolate, coffee, tea, or energy drinks should also be avoided during treatment with stiripentol.