Drug Interaction Report

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may significantly 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. 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: Pimavanserin dosage should be reduced to 10 mg once a day when used with potent CYP450 3A4 inhibitors.

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.

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.