Drug Interaction Report

Coadministration with probenecid may increase the plasma concentrations of olanzapine. The mechanism is probenecid inhibition of olanzapine glucuronidation via uridine diphosphoglucuronate-glucuronosyltransferase (UGT1A4). In 12 healthy volunteers, probenecid (500 mg orally twice a day) started one day before olanzapine administration (5 mg single dose) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of olanzapine by 18% and 26%, respectively, compared to administration of olanzapine alone. The clinical significance of this interaction and the effect during long-term administration is unknown.

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.