Drug Interaction Report

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 may decrease the plasma concentrations of pimavanserin, which is primarily metabolized by the isoenzyme. In a drug interaction study designed to measure pre- and post-pimavanserin levels following rifampin administration (a potent CYP450 3A4 inducer), Cmax and AUC were decreased by 71% and 91%, respectively, compared to pre-rifampin plasma concentrations. A physiologically based pharmacokinetic simulation with a moderate CYP450 3A4 inducer (efavirenz) predicted Cmax and AUC of pimavanserin will be decreased by approximately 60% and 70%, respectively.

MANAGEMENT: Coadministration of potent or moderate CYP450 3A4 inducers with pimavanserin should be avoided.

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.