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.

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.