[1] Side effects of elagolix include menopausal-like symptoms such as hot flashes, night sweats, insomnia, amenorrhea, mood changes, anxiety, and decreased bone density, among others.

[1] By blocking the GnRHR, it dose-dependently suppresses the gonadal production and hence circulating levels of sex hormones such as estradiol, progesterone, and testosterone.

[9] The introduction of elagolix in the United States and Canada was followed by that of relugolix (brand name Relumina), the next second-generation GnRH antagonist, in Japan in January 2019.

[8][16] The duration of use of elagolix in the treatment of endometriosis should be limited due to a progressive risk of bone loss, and the lowest effective dosage should be used.

[1] Other approved and off-label uses of GnRH antagonists in general are the same as those of GnRHR desensitization therapy with GnRH agonists such as leuprorelin, and include uterine fibroids and breast cancer in premenopausal women, prostate cancer in men, precocious puberty in children, and hormone therapy in transgender adolescents and adults, among others.

[1] Contraindications of elagolix include pregnancy, known osteoporosis, severe hepatic impairment, and concomitant use with strong organic anion-transporting polypeptide (OATP) 1B1 inhibitors such as ciclosporin and gemfibrozil.

[1] Women should avoid pregnancy while taking elagolix, for instance by using birth control, and should discontinue the medication if they become or wish to become pregnant.

[1] The most common side effects of elagolix (incidence ≥10%) are hot flashes, night sweats, headaches, nausea, and amenorrhea (cessation of menstruation).

[1][2][3] The next most frequent side effects of elagolix (incidence ≥5%) are insomnia, anxiety, arthralgia (joint pain), depression, and mood changes.

[1][2][3][16] Less common side effects of elagolix (incidence ≥3% and <5%) include decreased sex drive, diarrhea, abdominal pain, weight gain, dizziness, constipation, and irritability.

[1] Other common side effects of elagolix include decreased bone mineral density (BMD) and changes in the blood lipid profile.

[1][16] Other serious adverse effects of elagolix may include bone loss, miscarriage, suicidality, and elevated liver enzymes.

[1] Elagolix was discontinued due to side effects by 5 to 10% of women in clinical trials, with the most common reasons being hot flashes or night sweats, nausea, and decreased BMD.

[1] In women with risk factors for bone loss and osteoporosis, such as a history of low-trauma fracture, assessment of BMD may be considered.

[1] Supplementation with calcium and/or vitamin D during treatment with elagolix has not been studied, but may be beneficial for helping to maintain bone health.

[1] People taking elagolix with new or existing depressive symptoms should be promptly evaluated to determine whether the benefits of treatment outweigh the risks.

[1] In the event of an overdose of elagolix, the person should be monitored for any signs or symptoms of adverse reactions and should be treated on a symptomatic basis as needed.

[1] Chronic overdosage of elagolix may result in greater suppression of estradiol levels and a consequent increased risk of bone loss with long-term therapy.

[1] The strong CYP3A4 inhibitor ketoconazole has been found to increase peak levels of and total exposure to a single 150 mg dose of elagolix by about 2-fold.

[1] Paradoxically, rifampin, a strong inducer of CYP3A4 and other CYP450 enzymes, increased peak levels of and total exposure to a single 150 mg dose of elagolix as well.

[1] However, progestogens are antiestrogenic in the uterus, and high-dose progestin therapy is known to be effective in the treatment of endometriosis similarly to GnRH antagonists.

[1][26] In men, GnRH modulators suppress the testicular production of testosterone and estradiol, decreasing the circulating levels of these hormones similarly.

[6][5] In addition, due to its partial and incomplete suppression of estradiol levels, the side effects of elagolix, such as hot flashes and decreased BMD, are lower than with first-generation GnRH modulators.

[1] Because ovulation is triggered by a surge in estradiol levels at mid-cycle, estrogen exposure during elagolix therapy might be greater around this time in some women.

[6][9] Other small-molecule and non-peptide orally active GnRH antagonists besides elagolix include linzagolix, opigolix, relugolix, and sufugolix, although none of these compounds have been introduced for medical use at this time.

[9][10][25] In June 2010, Neurocrine Biosciences and Abbott announced a global agreement to develop and commercialize elagolix for the treatment of endometriosis.

[4] Two phase III clinical trials, the Elaris Endometriosis I and II (EM-I and EM-II) studies, were conducted.

[8][1][14] In September 2017, AbbVie filed a New Drug Application (NDA) for elagolix for the treatment of pain associated with endometriosis in the United States.

[37][38] Elagolix was the first member of a new class of GnRH modulators described as "second-generation" due to their non-peptide and small-molecule nature and oral activity to be marketed.

[6][9] An efficacy and safety study of elagolix in combination with add-back estradiol, an estrogen, and norethisterone acetate, a progestin, for the treatment of menorrhagia associated with uterine fibroids in premenopausal women has been published.