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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
Relugolix is an orally active nonpeptide GnRH-receptor antagonist used for the treatment of different sex hormone–related dysfunctions. The medication inhibits the release of gonadotropin from the pituitary, leading to reductions of estradiol, progesterone, and testosterone levels, without producing the initial upregulation of hormone levels associated with GnRH agonists such as leuprorelin. Relugolix was later approved for marketing in Japan as a medication for symptoms associated with uterine fibroids, and studies estimating the efficacy of the agent as a treatment for endometriosis-associated pain and prostate cancer have begun. The approved adult dosage of relugolix in Japan is 40 mg once daily, orally administered [76,77].
Novel treatment modalities
Published in Seema Chopra, Endometriosis, 2020
Relugolix (TAK-385) is a new oral GnRH-antagonist. A phase 2, open-label, RCT including 397 women with endometriosis-associated pain showed that Relugolix (10 mg, 20 mg, and 40 mg orally once daily) and Leuprolide (LEU) for 24 weeks are equally effective in treating pain symptoms [23]. An ongoing double-blind, placebo-controlled, phase 3 RCT is testing the efficacy and safety of Relugolix (40 mg once daily) co-administered with either 12 or 24 weeks of low-dose E2 (1 mg) and NETA (0.5 mg) in women with endometriosis-associated pain (NCT03204318) [24].
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
Relugolix (TAK385), an oral GnRH-antagonist, is mainly metabolized in the liver and has a half-life of 37–42 hours. Three different doses, 10 mg, 20 mg, and 40 mg once daily, were compared to a placebo as well as to the GnRH-agonist Leuprorelin in a phase II trial. Here, relugolix showed a reduction from baseline of mean pelvic pain score, quantified using the visual analog scale (VAS), as well as a reduction in dysmenorrhea. In comparison with leuprorelin, 40 mg relugolix showed a more rapid decrease in E2 and FSH levels, as well as a comparable occurrence of side effects, such as hot flashes and changes in bone mineral density. An open-label parallel group extension trial examined safety as a primary endpoint, measured by changes in BMD and occurrence of adverse events. Similar changes in BMD were found in the relugolix 40 mg group and in the leuprorelin group, notably −4.9% and −4.4%, respectively [21,26,27]. A phase-III trial evaluating the efficacy and safety of relugolix demonstrated a good tolerability and a low incidence of adverse events, such as loss of BMD, or vasomotoric symptoms. This study compared placebo to relugolix 40 mg with add-back and relugolix-mono therapy with a delayed intake of add-back therapy [28].
Relugolix in the management of prostate cancer
Published in Expert Review of Anticancer Therapy, 2022
Kamal Kant Sahu, Nishita Tripathi, Neeraj Agarwal, Umang Swami
Relugolix is an orally bioavailable GnRH antagonist that leads to rapid inhibition of testicular production of testosterone, which upon discontinuation is associated with a rapid recovery of serum testosterone level within a few weeks. This attribute may position relugolix as a preferred agent in those interested in intermittent ADT and who desire rapid recovery of testosterone during ‘drug holiday’ periods. Relugolix was associated with a superior cardiovascular safety profile compared to GnRH agonists in the phase III HERO trial [57]. Also, in the subgroup analysis of the Hero trial, investigators reported that relugolix was well tolerated when given concurrently with cardiovascular medications (Antihypertensives, antithrombotic agents, and lipid-modifying drugs) [59,60]. Hence, the above-mentioned characteristics make relugolix a preferred agent over androgen agonists as monotherapy due to the superior cardiovascular safety profile, and minimal interactions with the cardiovascular medications.
Relugolix: A new kid on the block among gonadotrophin-releasing hormone antagonists
Published in Arab Journal of Urology, 2021
Charalampos Fragkoulis, Ioannis Glykas, Athanasios Dellis, Iraklis Mitsogiannis, Athanasios Papatsoris
The pivotal phase III study of relugolix that led to FDA approval was published recently by Shore et al. [7]. The investigators randomly stratified patients diagnosed with advanced prostate cancer either to receive relugolix or leuprolide for a treatment period of 48 weeks. Relugolix was administered orally at a single loading dose of 320 mg followed by 120 mg daily. While leuprolide was administered by injection every 3 months. The study’s primary end-point was the achievement of a sustained testosterone suppression to castrate levels during the treatment period. Secondary end-points such as non-inferiority regarding the primary end-point, testosterone levels on day 4 and castration levels set at <20 ng/dL on day 15 were also evaluated. Relugolix managed to suppress testosterone and maintain castration levels in a superior way compared with leuprolide. Apart from superiority regarding the primary end-point, relugolix demonstrated superiority over leuprolide in all secondary end-points as well. In a subgroup of 184 patients, testosterone recovery evaluation was possible. The mean testosterone levels 3 months after treatment cessation were 288.4 ng in the relugolix arm and 58.6 ng in the leuprolide arm. Furthermore, relugolix was safer in terms of risk of major cardiovascular events presenting a 54% lower risk.