Drug Interactions between amoxicillin / clarithromycin / omeprazole and elagolix

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.

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.

Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.