Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 1A2 may decrease the plasma concentrations of olanzapine. Data from available studies indicate that olanzapine is primarily metabolized by CYP450 1A2 and, to a lesser extent, by CYP450 2D6 and uridine diphosphate glucuronosyltransferase (UGT) 1A4. When coadministered with rifampin, a moderate CYP450 1A2 inducer that also induces UGT 1A4, olanzapine peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 11% and 48%, respectively. Coadministration with 200 mg twice daily of carbamazepine, another CYP450 1A2 inducer, caused an approximately 50% increase in the clearance of olanzapine. Higher daily dosages of carbamazepine may cause an even greater increase in olanzapine clearance.

MANAGEMENT: The potential for diminished pharmacologic effects of olanzapine should be considered during coadministration with CYP450 1A2 inducers. Alternative treatments may be required if an interaction is suspected.

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of samidorphan. According to the prescribing information, samidorphan is primarily metabolized by CYP450 3A4, with minor contributions from CYP450 2C8, 2C19, and 3A5. When olanzapine-samidorphan was coadministered with rifampin, a potent CYP450 3A4 inducer, samidorphan peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 44% and 73%, respectively. Olanzapine Cmax and AUC also decreased by 11% and 48%, respectively, most likely due to induction of CYP450 1A2 and/or uridine diphosphate glucuronosyltransferase (UGT) 1A4 by rifampin.

MANAGEMENT: Concomitant use of olanzapine-samidorphan with potent CYP450 3A4 inducers is not recommended.

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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.