Drug Interactions between pitolisant and propoxyphene

GENERALLY AVOID: Limited data suggest that pitolisant may produce mild to moderate QT interval prolongation (10 to 13 milliseconds) at doses 3 to 6 times the standard therapeutic dose. In addition, coadministration with inhibitors of the CYP450 2D6 isoenzyme may increase plasma concentrations of pitolisant, which is a substrate of this isoenzyme. Theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. The risk of an individual agent or a combination of these agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). The extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). Coadministration with the CYP450 2D6 inhibitor paroxetine was reported to increase the mean peak plasma concentration (Cmax) of pitolisant by approximately 47% and result in a 2-fold increase in its systemic exposure. However, clinical data are not available.

MANAGEMENT: Concomitant use of pitolisant with other agents associated with QT interval prolongation and CYP450 2D6 inhibition should generally be avoided. Caution and clinical monitoring are recommended if concomitant use is required. Dosage adjustment of pitolisant may be considered. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.