Drug Interactions between AccessPak for HIV PEP Expanded with Viracept 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.

MONITOR: Coadministration with elagolix may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) transporter. The proposed mechanism is decreased clearance in the intestine, kidney, and/or liver due to inhibition of P-gp-mediated efflux by elagolix. When a single 0.5 mg dose of the probe P-gp substrate digoxin was coadministered with elagolix (200 mg twice daily for 10 days) in 11 study subjects, digoxin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 71% and 26%, respectively, compared digoxin administered alone.

MANAGEMENT: Caution is advised when elagolix is used concurrently with drugs that are P-gp substrates, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever elagolix is added to or withdrawn from therapy.