Drug Interaction Report

Coadministration with inhibitors of CYP450 3A4 is not expected to significantly affect the pharmacokinetics of citalopram or escitalopram, both of which are partially metabolized by the isoenzyme. Administration of racemic citalopram (40 mg) in combination with the potent CYP450 3A4 inhibitor ketoconazole (200 mg) decreased the ketoconazole peak plasma concentration (Cmax) by 21% and systemic exposure (AUC) by 10%, but did not significantly affect the pharmacokinetics of citalopram. Likewise, coadministration of a single 20 mg dose of escitalopram with a single 600 mg dose of ritonavir, another potent CYP450 3A4 inhibitor, did not affect the pharmacokinetics of either drug. Because citalopram and escitalopram are both metabolized by multiple isoenzymes (CYP450 2C19, 3A4, and 2D6), inhibition of a single isoenzyme may not appreciably decrease their clearance.

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.