Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of pimavanserin, which is primarily metabolized by the isoenzyme. According to the product labeling, pimavanserin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.5- and 3-fold, respectively, when given with the potent CYP450 3A4 inhibitor ketoconazole. The interaction has not been studied with other, less potent inhibitors. High plasma levels of pimavanserin may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Caution is advised when pimavanserin is used with CYP450 3A4 inhibitors. Patients should be monitored for adverse effects such as peripheral edema and QT prolongation, and the pimavanserin dosage adjusted as necessary.