Relugolix is approved in Japan for the treatment of uterine fibroids in women. It is used at a dosage of 40 mg once daily by mouth for this indication.
Available forms
Relugolix is available in the form of 40 mg oral tablets.
Relugolix is a selective antagonist of the gonadotropin-releasing hormone receptor, with a half-maximal inhibitory concentration of 0.12 nM. A dosage of relugolix of 40 mg once per day has been found to suppress estradiol levels to postmenopausal levels within 24 hours in premenopausal women. In the control group of women, estradiol levels fluctuated between 50 and 250 pg/mL. Estradiol levels have been found to return to normal concentrations within 4 weeks of discontinuation of relugolix in premenopausal women. The medication additionally suppresses levels of progesterone, luteinizing hormone, and follicle-stimulating hormone in premenopausal women. Relugolix at a dosage of 40 mg or more once per day has been found to reduce testosterone levels to sustained castrate levels in men. It additionally suppresses luteinizing hormone and follicle-stimulating hormone levels in men. Lower doses of relugolix are under investigation for achieving partial sex hormone suppression in the treatment of endometriosis and uterine fibroids. This is intended to reduce the incidence and severity of menopausal symptoms such as hot flushes and decreased bone mineral density that are secondary to estrogen deficiency.
Pharmacokinetics
A single 40-mg oral dose of relugolix has been found to result in peak levels of relugolix of 29 ng/mL after 1.5 hours. Steady-state levels are reached within 7 days with 40 mg/day relugolix administration. There is an approximate 2-fold accumulation of relugolix by 2 weeks of continuous administration. Food diminishes the oral bioavailability of relugolix by about 50%. Relugolix is a substrate for P-glycoprotein, which may have a limiting effect on its absorption and distribution. The plasma protein binding of relugolix is approximately 68 to 71% over a concentration range of 0.05 to 5 μg/mL. Relugolix is not a substrate for CYP3A4. The elimination half-life of relugolix is 36 to 65 hours across a dosage range of 20 to 180 mg/day. There is moderate to high interindividual variability in systemic exposure to relugolix. Relugolix is excreted mainly in feces and to a small degree in urine. Only about 6% of a dose of relugolix is excreted unchanged.
Chemistry
Relugolix is a non-peptide, small-molecule compound, and is structurally distinct from GnRH analogues. It is an N-phenylurea derivative.
History
Relugolix was first described in 2004. It superseded sufugolix, which was developed by the same researchers. Relugolix was approved for the treatment of uterine fibroids in Japan on 8 January 2019. It was the second orally active GnRH antagonist to be introduced for medical use, following elagolix in July 2018.
Society and culture
Generic names
Relugolix is the generic name of the drug and its,, and. It is also known by its former developmental code namesRVT-601 and TAK-385.
Brand names
Relugolix is marketed under the brand name Relumina.
Availability
Relugolix is available in Japan.
Research
Relugolix is under development by Myovant Sciences and Takeda for the treatment of uterine fibroids in countries besides Japan such as the United States. Myovant Sciences intends to submit a New Drug Application of relugolix for uterine fibroids in the United States in the fourth quarter of 2019. Relugolix is also under development for the treatment of endometriosis and prostate cancer in the United States, Japan, and other countries. As of February 2019, it is in phase III clinical trials for these indications.
