What is the use of Relugolix (Generic name: Relugolix)?

From the Guidelines

Relugolix is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist used to treat hormone-sensitive conditions, specifically uterine fibroids, by rapidly suppressing sex hormones and reducing bleeding symptoms 1.

Mechanism of Action

Relugolix works by blocking GnRH receptors in the pituitary gland, reducing the production of luteinizing hormone and follicle-stimulating hormone. This mechanism is effective in reducing tumor volume and is commonly used for short courses to decrease fibroid size in preparation for surgery 1.

Medical Management

Relugolix is considered a second-line medical management option for uterine fibroids, along with other oral GnRH antagonists such as elagolix and linzagolix 1. It is often used in combination with low doses of estrogen and progestin to mitigate hypoestrogenic effects, including headaches, hot flushes, hypertension, and loss of bone mineral density.

Treatment Options

For women with uterine fibroids, relugolix is typically prescribed as a combination therapy, including relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg, taken once daily 1. This treatment option is FDA-approved for fibroid-related heavy menstrual bleeding and is often chosen by women interested in uterus-preserving therapy or preservation of future fertility.

Side Effects and Risks

Common side effects of relugolix include hot flashes, fatigue, and potential bone mineral density loss with long-term use 1. Patients should be monitored for cardiovascular risks, as the medication may increase the risk of heart-related events. Unlike traditional GnRH agonists, relugolix does not cause an initial testosterone surge, making it advantageous for patients with symptomatic disease requiring rapid hormone suppression 1.

From the FDA Drug Label

Relugolix is a nonpeptide small molecule, GnRH receptor antagonist The chemical name is N-(4-{1-[(2,6-difluorophenyl)methyl]-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl}phenyl)-N'-methoxyurea. Relugolix reduced LH, FSH, and testosterone concentrations after oral administration of the recommended loading dose of 360 mg and a 120 mg dose once daily Relugolix is a nonpeptide GnRH receptor antagonist that competitively binds to pituitary GnRH receptors, thereby, reducing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and consequently testosterone.

The use of Relugolix is as a GnRH receptor antagonist to reduce the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and consequently testosterone.

• The recommended dose is 120 mg daily.
• The mechanism of action is by competitively binding to pituitary GnRH receptors.
• The effect is to reduce LH, FSH, and testosterone concentrations 2

From the Research

Use of Relugolix

The use of Relugolix, also known as Relugolix combination therapy, is primarily for the management of:

• Heavy menstrual bleeding associated with uterine fibroids 3
• Moderate to severe pain associated with endometriosis 3, 4, 5, 6, 7
• Symptoms associated with uterine fibroids in the European Union and the United Kingdom 3
• Advanced prostate cancer in men, where Relugolix suppresses testosterone production 3

Mechanism of Action

Relugolix is an orally active, nonpeptide, GnRH receptor antagonist that:

• Competitively binds to GnRH receptors, preventing the release of follicle-stimulating hormone and luteinizing hormone (LH) into the systemic circulation 3
• Reduces circulating concentrations of estradiol (E2) and progesterone (P), improving heavy menstrual bleeding and other symptoms associated with uterine fibroids and endometriosis 3

Combination Therapy

Relugolix combination therapy includes:

• Relugolix 40 mg
• Estradiol 1 mg
• Norethindrone acetate 0.5 mg This combination allows for the mitigation of hypoestrogenic effects, including bone mineral density loss and vasomotor symptoms, while maintaining therapeutic efficacy 3, 4, 5, 6, 7

Efficacy and Safety

Studies have shown that Relugolix combination therapy:

• Significantly improves dysmenorrhea and non-menstrual pelvic pain in premenopausal women with moderate to severe endometriosis 4, 6, 7
• Reduces overall pelvic pain and dyspareunia, and improves health-related quality of life 4, 6
• Is generally well tolerated, with common adverse events including headache, nasopharyngitis, and hot flushes 6, 7