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Pharmacologic response to quetiapine should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the quetiapine dosage adjusted as necessary.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: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.