Drug Interaction Report

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of atogepant, which is primarily metabolized by the isoenzyme. When atogepant was administered with the potent CYP450 3A4 inhibitor itraconazole in healthy study subjects, atogepant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 2.2- and 5.5-fold, respectively.

MANAGEMENT: The recommended dosage of atogepant is 10 mg once daily when used concomitantly with potent CYP450 3A4 inhibitors.

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.