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.

Administration with food may delay the absorption of modafinil (the racemate) and armodafinil (the R-enantiomer) without significantly affecting their overall bioavailability. According to the product labeling, modafinil's absorption may be delayed by approximately one hour if taken with food. Similarly, the time to reach peak plasma concentration (Tmax) of armodafinil may be delayed by approximately 2 to 4 hours in the fed state.