Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of quetiapine, which is primarily metabolized by the isoenzyme. In 18 psychiatric patients receiving quetiapine 300 mg twice daily, addition of the potent CYP450 3A4 inducer carbamazepine (200 mg three times daily) decreased mean quetiapine peak plasma concentration (Cmax) and systemic exposure (AUC) by 80% and 87%, respectively, and increased oral clearance (Cl/F) by 7.5-fold compared to quetiapine administered alone. The interaction has also been reported with phenytoin, another potent CYP450 3A4 inducer. In ten subjects with various affective disorders, coadministration of quetiapine (250 mg orally three times a day) with phenytoin (100 mg orally three times a day) decreased the mean steady-state Cmax, trough plasma concentration (Cmin) and AUC of quetiapine by 66%, 89% and 80%, respectively. The mean oral clearance increased by 5.5-fold. No data are available for other, less potent CYP450 3A4 inducers.

MANAGEMENT: Pharmacologic response to quetiapine should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the quetiapine dosage adjusted as necessary. Patients should be advised to notify their physician if their symptoms worsen or their condition changes.

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.