Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of elagolix, which is a substrate of the isoenzyme. In 11 study subjects, administration of a single 150 mg dose of elagolix with 400 mg once daily dosing of ketoconazole, a potent CYP450 3A4 inhibitor, increased elagolix peak plasma concentration (Cmax) and systemic exposure (AUC) by 77% and 120%, respectively, compared to elagolix administered alone. Increased exposure to elagolix may increase the risk of serious adverse effects such as bone loss, suicidal ideation and behavior, exacerbation of mood disorders, and hepatic transaminase elevations.

MANAGEMENT: Concomitant use of elagolix 200 mg twice daily with potent CYP450 3A4 inhibitors for more than 1 month, or elagolix 150 mg once daily with potent CYP450 3A4 inhibitors for more than 6 months, is not recommended.

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.

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.