Drug Interactions between amoxicillin / clarithromycin / vonoprazan and pitolisant

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. 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. In general, 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). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drugs.

MANAGEMENT: Concomitant use of pitolisant with other agents associated with QT interval prolongation should generally be avoided. 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.

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of vonoprazan, which is metabolized by the isoenzyme. When coadministered with potent and moderate CYP450 3A4 inducers, vonoprazan systemic exposure (AUC) is predicted to decrease by 80% and 50%, respectively. No data are available for other, less potent CYP450 3A4 inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of vonoprazan should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.