Drug Interaction Report

MONITOR: Coadministration with pitolisant may decrease the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. Pitolisant is a borderline/weak inducer of CYP450 3A4. When studied with midazolam, a probe substrate for CYP450 3A4, pitolisant was found to reduce midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) by less than 25%.

MANAGEMENT: Caution is advised when pitolisant is used in combination with sensitive CYP450 3A4 substrates. Clinical and laboratory monitoring may be appropriate whenever pitolisant is added to or withdrawn from therapy, and dosage adjustments made if necessary. It may be advisable to avoid concomitant use of pitolisant and CYP450 3A4 substrates with a narrow therapeutic index, if possible.

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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.