Elagolix is an oral gonadotropin-releasing hormone receptor antagonist indicated 
for the management of endometriosis-associated pain and in combination with 
estradiol/norethindrone acetate indicated for the management of heavy menstrual 
bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. 
Elagolix coadministered with estradiol/norethindrone acetate is in late-stage 
development for the management of heavy menstrual bleeding associated with 
uterine fibroids. Based on the in vitro profile of elagolix metabolism and 
disposition, 9 drug-drug interaction (DDI) studies evaluating the victim and 
perpetrator characteristics of elagolix were conducted in 144 healthy 
volunteers. As a victim of cytochrome P450 (CYPs) and transporter-mediated DDIs, 
elagolix area under the curve (AUC) increased by ∼2-fold following 
coadministration with ketoconazole and by ∼5- and ∼2-fold with single and 
multiple doses of rifampin, respectively. As a perpetrator, elagolix decreased 
midazolam AUC (90% confidence interval) by 54% (50%-59%) and increased digoxin 
AUC by 32% (23%-41%). Elagolix decreased rosuvastatin AUC by 40% (29%-50%). No 
clinically significant changes in exposure on coadministration with sertraline 
or fluconazole occurred. A elagolix 150-mg once-daily regimen should be limited 
to 6 months with strong CYP3A inhibitors and rifampin because of the potential 
increase in bone mineral density loss, as described in the drug label. A 200-mg 
twice-daily regimen is recommended for no more than 1 month with strong CYP3A 
inhibitors and not recommended with rifampin. Elagolix is contraindicated with 
strong organic anion transporter polypeptide B1 inhibitors (eg, cyclosporine and 
gemfibrozil). Consider increasing the doses of midazolam and rosuvastatin when 
coadministered with elagolix, and individualize therapy based on patient 
response. Clinical monitoring is recommended for P-glycoprotein substrates with 
a narrow therapeutic window (eg, digoxin). Dose adjustments are not required for 
sertraline, fluconazole, bupropion (or any CYP2B6 substrate), or elagolix when 
coadministered.