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Endometriosis
Published in S Paige Hertweck, Maggie L Dwiggins, Clinical Protocols in Pediatric and Adolescent Gynecology, 2022
Available in oral or intramuscular formsElagolix 150 mg daily or 200 mg twice dailyIs not approved for use in women under age 18
Chronic pelvic pain and endometriosis
Published in Joseph S. Sanfilippo, Eduardo Lara-Torre, Veronica Gomez-Lobo, Sanfilippo's Textbook of Pediatric and Adolescent GynecologySecond Edition, 2019
Joseph S. Sanfilippo, Jessica Papillon Smith, M. Jonathon Solnik
More recently, the safety and efficacy of oral GnRH antagonists have been evaluated for the treatment of endometriosis in the adult population. This drug acts by competitively inhibiting the GnRH receptors in the pituitary gland, resulting in a rapid decrease in circulating gonadotropins and estradiol. Recent randomized phase 2 and phase 3 trials have demonstrated the ability of GnRH antagonists to significantly reduce the symptoms related to moderate and severe endometriosis.78 However, these agents were also found to result in hypoestrogenic side effects, including reduced BMD, increased lipid levels, and vasomotor symptoms.78 The pharmaceutical name, Elagolix, is now approved in the United States and Canada under the trade name, Orlissa. Partial suppression can be achieved with a dose of 150 mg daily (for up to 24 months) and full suppression with a higher regimen of 200 mg twice daily (for up to 6 months). Addback therapy is recommended with use of the higher dosing to reduce the risk of bone loss. Elagolix should not be considered a contraceptive and estrogen-containing contraceptive options have been shown to reduce efficacy so consideration towards progestin-only options or barrier protection should be used if appropriate. Studies using this drug in the adolescent population are lacking.
Medical Options for Uterine Fibroids in the Context of Reproduction
Published in Botros R.M.B. Rizk, Yakoub Khalaf, Mostafa A. Borahay, Fibroids and Reproduction, 2020
Hoda Elkafas, Mona Al Helou, Qiwei Yang, Ayman Al-Hendy
Currently, available treatment options are restricted, and approved market medications are often used for short-term treatment to control HMB. Progestogens and COCs usually provide a brief improvement in HMB. The LNG-IUS is valuable in decreasing bleeding, but it is used only in women with a normal uterine cavity. These medications reduce bleeding by targeting the endometrium and do not diminish fibroid volume. GnRH agonists are highly effective in suppressing bleeding and reducing fibroids and uterine mass. Leuprolide acetate is FDA approved for presurgery short-term treatment. No hormonal add-back therapies have been approved as GnRH agonists for long-term treatment of fibroids. However, some medications currently under investigation in the United States, such as PRMs and oral GnRH antagonists, offer a promise of new fertility-sparing medical therapies that could provide a long-term treatment option for women with fibroids. Alternative treatment using UPA has recently been approved in Europe and Canada for the long-term management of symptomatic fibroids. Vilaprisan has been evaluated only in women with symptomatic fibroids, and it has an advantage over other SPRMs, such as UPA. Vilaprisan exhibits more rapid action on bleeding related to fibroids but shows effects with lower doses than other SPRMs. Elagolix is an FDA-approved oral treatment for controlling endometriosis with symptoms from a moderate to severe degree. A recent phase IIb study of therapy with elagolix combined with low-dose add-back therapy exhibited high efficiency and improvements in HMB. This combination treatment shows a low rate of hypoestrogenic side effects such as vasomotor signs and changes in BMD. Continuous studies of the pathogenesis of uterine fibroids and a new pharmacological target, nonhormonal effect, and long-term medical regimen to eradicate this disease are needed.
Deciding on the appropriate pharmacotherapy for the treatment of endometriosis
Published in Expert Opinion on Pharmacotherapy, 2023
Oral GnRH-antagonists represent a new option in the medical treatment of endometriosis. Initial results using Elagolix show a better side-effect profile when compared to GnRHa with significant reduction in endometriosis-related pain when compared to placebo [18]. Advantages include the lack of flare-up effects, a rapid reduction in estradiol levels and availability of two different doses (150 mg/day and 200 mg twice daily). Drawbacks include vasomotor symptoms, osteopenia and osteoporosis in higher doses related to hypoestrogenism and the possibility of ovulation in lower doses. Elagolix has not been compared to standard options in the treatment of endometriosis such as GnRHa or progestogens, so it might be too early to celebrate its effects [19]. There are two other oral GnRH-antagonists for which trials are still ongoing. Relugolix has shown benefits in alleviating pain in comparison to leuprorelin in a phase 3, multicenter, randomized, double-blind controlled trial in Japan [20].
The latest advances in the pharmacological management of endometriosis
Published in Expert Opinion on Pharmacotherapy, 2023
Gabriel Hartner, Heinrich Husslein, Lorenz Kuessel, Manuela Gstoettner, Denise Tiringer, René Wenzl, Alexandra Perricos
Elagolix is the first GnRH antagonist commercially available that can be administered orally because of its non-peptide structure. It has been approved for the treatment of heavy to moderate symptoms caused by endometriosis in premenopausal women with a dose of 150 mg once daily or 200 mg twice daily, depending on the patient’s symptoms. This approval was based on studies on women with surgically documented endometriosis. While the best efficacy in pain management was observed with a dose of 200 mg twice daily, the high dose went hand in hand with a higher occurrence of adverse events. These side effects, associated with the hypoestrogenic state, include nausea, hot flashes, a decrease in bone mineral density (BMD), mood swings, and an increase in serum lipid levels. Similar to GnRH-agonists, the treatment duration of elagolix is limited to 6 months with doses of 200 mg twice daily (for the treatment of dyspareunia) or 24 months with doses of 150 mg once daily, in patients without hepatic impairment. Contraception during intake of elagolix is advised, as clinical trials on 3500 women reported pregnancies in 49 study participants who received this GnRH antagonist. Furthermore, congenital malformations were observed in two pregnancies after treatment with a daily dose of 150 mg [18]. Further research is directed toward examining the pain-relieving effect of elagolix in combination with add-back therapy (usually in the form of a progestin or estrogen/progestin combination), hoping to prolong the approved treatment duration of the GnRH antagonist by counteracting its hypoestrogenic side-effects [12,13,19,20].
Current approaches to overcome the side effects of GnRH analogs in the treatment of patients with uterine fibroids
Published in Expert Opinion on Drug Safety, 2022
Mohamed Ali, Mohamed Raslan, Michał Ciebiera, Kornelia Zaręba, Ayman Al-Hendy
A clinical review on elagolix showed that the most prevalent side effects were mild-to-moderate nausea and hot flashes, with the highest incidence of hot flashes occurring in women receiving a dosage of at least 200 mg twice a day. Spotting was also observed by seven participants in a phase 1 investigational study [62,63]. In a phase II trial of endometriosis patients, both elagolix 150 mg and 250 mg groups exhibited a substantial reduction in bone mineral density (BMD) where a substantial dose-dependent decline in lumbar BMD was seen in both groups following 6 months of therapy [64]. Additionally, phase III trial showed an elagolix-related rise in low-density and high-density lipoprotein cholesterol, as well as triglycerides [63]. In another clinical study, it was found that the adverse reactions appeared in women treated with elagolix plus addback therapy, resulting in therapy discontinuation in some of them. The most common reported side events were nausea, headache, alopecia, metrorrhagia, menorrhagia and hot flushes (reported in 1% each). Add-back treatment reduced elagolix’s hypoestrogenic effects, particularly BMD loss, but hot flushes and metrorrhagia occurred considerably more frequently than placebo [65].