Drug Interaction Report

MONITOR: Coadministration with CYP450 3A4 inducers may decrease the plasma concentration and pharmacologic effects of ritlecitinib. The proposed mechanism is increased clearance of ritlecitinib due to induction of the CYP450 3A4 isoenzyme, one of the pathways of elimination of ritlecitinib. When a single 50 mg dose of ritlecitinib was administered in combination with the potent CYP450 3A4 inducer rifampin (600 mg once daily for 8 days), the mean peak plasma concentration (Cmax) and systemic exposure (AUC) of ritlecitinib decreased by approximately 25% and 44%, respectively, compared to ritlecitinib administered alone. Data are not available of other, less potent inducers.

MANAGEMENT: Caution is advised when ritlecitinib is used with CYP450 3A4 inducers. The possibility of diminished therapeutic effects should be considered.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of rufinamide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of rufinamide. In healthy volunteers, administration of a single 400 mg dose of rufinamide with food resulted in an approximately 56% increase in mean peak plasma concentration (Cmax) and a 34% increase in systemic exposure (AUC) compared to administration during a fasting state.

MANAGEMENT: To ensure maximal oral absorption, it is preferable to administer rufinamide with food. Patients receiving rufinamide should be advised to avoid consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how rufinamide affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.