Drug Interaction Report

ADJUST DOSE: Coadministration with potent CYP450 3A4 inducers may decrease the systemic exposure and efficacy of pitolisant. The proposed mechanism is induction of CYP450 3A4-mediated metabolism of pitolisant, which has been shown to be metabolized by this isoenzyme. Concomitant use with the potent CYP450 3A4 inducer rifampin decreased the mean peak plasma concentration (Cmax) and area under the plasma concentration-time curve ratio (AUC ratio) by 39% and 50%, respectively.

MANAGEMENT: Patients should be assessed for loss of efficacy of pitolisant following initiation of a potent CYP450 3A4 inducer, and the pitolisant dosage adjusted as necessary. For patients already receiving a stable dose of pitolisant 8.9 mg or 17.8 mg once daily, the dose of pitolisant should be increased to double the original daily dose (i.e., 17.8 mg or 35.6 mg, respectively) over 7 days. The dosage of pitolisant should be reduced by half if concomitant use of a strong CYP450 3A4 inducer is discontinued.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.