Endolix 150

Endometriosis

Take at approximately the same time each day, with or without food

Endometriosis Indicated for management of moderate-to-severe pain associated with endometriosis Initiate with 150 mg PO qDay for up to 24 months Hepatic impairment Mild (Child-Pugh A): No dosage adjustment required Moderate (Child-Pugh B): Only the 150-mg qDay regimen is recommended for women with moderate hepatic impairment, and the duration of treatment should be limited to 6 months Severe (Child-Pugh C): Contraindicated

Renal impairment No dosage adjustment required with any degree of renal impairment or end-stage renal disease (including dialysis)

Pregnancy Known osteoporosis Severe hepatic impairment Coadministration of strong organic anion transporting polypeptide (OATP) 1B1 inhibitors (eg, cyclosporine and gemfibrozil)

Oral gonadotropin-releasing hormone (GnRH) receptor antagonist; inhibits endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland Administration of elagolix results in dose-dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased blood concentrations of the ovarian sex hormones, estradiol and progesterone

May reduce the amount, intensity, or duration of menstrual bleeding, which may decrease the ability to recognize the occurrence of a pregnancy in a timely manner; perform pregnancy testing if pregnancy is suspected, and discontinue drug if pregnancy confirmed Dose-dependent elevations of ALT >3x ULN occurred with elagolix; use the lowest effective dose and instruct patients to promptly seek medical attention in case of symptoms or signs that may reflect liver injury Suicidal behavior and mood disorders Suicidal ideation and behavior, including 1 completed suicide, occurred in subjects treated with elagolix in the endometriosis clinical trials Patients taking elagolix had a higher incidence of depression and mood changes compared with placebo Patients with a history of suicidality or depression had a higher incidence of depression compared with subjects without such a history Promptly evaluate patients with depressive symptoms to determine whether the risks of continued therapy outweigh the benefits Patients with new or worsening depression, anxiety, or other mood changes should be referred to a mental health professional, as appropriate Advise patients to seek immediate medical attention for suicidal ideation and behavior Reevaluate the benefits and risks of continuing elagolix if such events occur

>10% Hot flush or night sweats (24-36%) Headache (17-20%) Nausea (11-16%) 1-10% Insomnia (6-9%) Mood altered, mood swings (5-6%) Amenorrhea (4-7%) Depressed mood, depression, depressive symptoms and/or tearfulness (3-6%) Hypersensitivity reactions (5.8%) Anxiety (3-5%) Arthralgia (3-5%)

Pregnancy Contraindicated in pregnant women Drug exposure early in pregnancy may increase the risk of early pregnancy loss Discontinue elagolix if pregnancy occurs during treatment The limited human data with use in pregnant women are insufficient in determining whether there is a risk for major birth defects or miscarriage; although 2 cases of congenital malformations were reported in clinical trials with elagolix, no pattern was identified and miscarriages were reported at a similar incidence across treatment groups Animal data When pregnant rats and rabbits were orally dosed with elagolix during the period of organogenesis, postimplantation loss was observed in pregnant rats at doses 20 times the maximum recommended human dose (MRHD) Spontaneous abortion and total litter loss was observed in rabbits at doses 7 and 12 times the MRHD There were no structural abnormalities in the fetuses at exposures up to 40 and 12 times the MRHD for the rat and rabbit, respectively Pregnancy testing Exclude pregnancy before initiating treatment with elagolix Perform pregnancy testing if pregnancy is suspected during treatment with elagolix Contraception Advise women to use effective nonhormonal contraception during treatment with elagolix and for 1 week after discontinuing elagolix Lactation There is no information on the presence of elagolix or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production There are no adequate animal data on the excretion of elagolix in milk The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for elagolix and any potential adverse effects on the breastfed child from elagolix