Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of pimavanserin, which is primarily metabolized by the isoenzyme. A drug interaction study has shown decreases in pimavanserin Cmax (71%) and AUC (91%) with coadministration of rifampin, a strong CYP450 3A4 inducer. 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: The possibility of diminished therapeutic response to pimavanserin should be considered during coadministration with CYP450 3A4 inducers. The manufacturer recommends coadministration with strong or moderate CYP450 3A4 inducers be avoided.

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

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of rufinamide. In healthy volunteers, administration of a single 400 mg dose of rufinamide with food resulted in an approximately 56% increase in mean peak plasma concentration (Cmax) and a 34% increase in systemic exposure (AUC) compared to administration during a fasting state.

MANAGEMENT: To ensure maximal oral absorption, it is preferable to administer rufinamide with food. Patients receiving rufinamide should be advised to avoid consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how rufinamide affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.