Relugolix an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, for the treatment of adults with advanced prostate cancer.
It is the only oral androgen deprivation therapy option and provides an alternate route of administration, compared to long acting injectable agents which include degarelix, a GnRH antagonist and GnRH, agonists goseerelin, leuprolide, triptorelin.
It is an oral highly selective LHRH antagonist.
Sold under the brand name Orgovyx.
A once daily oral option with rapid testosterone suppression, and recovery.
A gonadotropin-releasing hormone antagonist (GnRH receptor antagonist) medication.
A GnRH antagonist, or an antagonist of the gonadotropin-releasing hormone receptor.
It achieves both luteinizing hormone and follicle-stimulating hormone suppression due to its direct inhibitory effect in the pituitary GnRH receptors.
It’s direct inhibition does not result in a testosterone surge.
The primary pharmacologic differences between GnRH agonists and antagonists, are the onset of action and the testosterone flare, which are both related to the innate impact on the hypothalamic pituitary gonadal access.
Relugolix is a non-peptide, small-molecule compound, and is structurally distinct from GnRH analogues.
The first oral hormone therapy for the treatment of adults with advanced prostate cancer.
Relugolix is the first oral androgen-deprivation therapy (ADT) and the first oral GnRH receptor antagonist approved for patients with advanced prostate cancer.
Phase 3 HERO trial in men with advanced prostate cancer.
Participants randomly received either relugolix once daily or injections of leuprolide (Lupron), another hormone-targeting drug, every 3 months for 48 weeks.
Of the 622 patients who received relugolix, the castration rate was revealed to be 96.7%.
Most common adverse events included: hot flush (54%), increased glucose (44%), increased triglycerides (35%), musculoskeletal pain (30%), decreased hemoglobin (28%), fatigue (26%), constipation (12%), diarrhea (12%), and increased levels of liver enzymes.
The concurrent use of relugolix with drugs that inhibit P-glycoprotein, which plays a role in pumping toxins out of cells, is contraindicated.
It may affect the heart’s electrical properties or cause electrolyte abnormalities, and should be considered for periodic monitoring of electrocardiograms and electrolytes.
It can cause fetal harm and loss of pregnancy when administered to a pregnant female.
It is advised that males with female partners of reproductive potential use effective contraception during treatment and for 2 weeks after the last dose of relugolix.
Pituitary gonadotropic and gonadal functions conducted during and after taking relugolix may be affected due to the drug’s suppression of the pituitary gonadal system.
Routes of administration-oral.
The GnRH antagonist is giving once daily orally, with an effective half-life of 25 hours.
It rapidly inhibits pituitary release of luteinizing hormone and FSH, and lowers testosterone levels.
In patients with prostate cancer results is in rapid sustained suppression of testosterone levels superior to that with leuprolide with a 54% lower risk of major adverse cardiovascular events.
It suppresses sex hormone levels to the postmenopausal or castrate range in both women and men with administration once per day.
Drug class GnRH antagonist
Protein binding 68–71%.
Elimination half-life 36 to 65 hours.
Excretion by feces: 82%.
Urine: 4%
Side effects include: menstrual abnormalities, hot flashes, excessive sweating, headache, and decreased bone mineral density.
A non-peptide, small-molecule compound and is orally active.
It suppresses sex hormone levels to the postmenopausal or castrate range in both women and men with administration once per day.
In phase III clinical trials for endometriosis and prostate cancer.
Phase3HERO trial demonstrated superiority over leuprolide in sustained testosterone suppression through 48 weeks, fast testosterone recovery after discontinuation, and a 50% reduction in major adverse cardiovascular events in patients with advanced prostate cancer.
Overall men treated with relugolix maintain castration levels androgen through week 48 compared with 88.8% on leuprolide.
Useful in the treatment of uterine fibroids.
40 mg once daily by mouth.
Side effects of relugolix include abnormal uterine bleeding, hot flashes, heavy menstrual bleeding, headache and excessive sweating.
Decreased bone mineral density occurs with relugolix use.
It is a selective antagonist of the gonadotropin-releasing hormone receptor (GnRHR).
40 mg once per day has been found to suppress estradiol levels to postmenopausal levels (<20 pg/mL) within 24 hours in premenopausal women.
Estradiol levels return to normal concentrations within 4 weeks of discontinuation of relugolix in premenopausal women.
In premenopausal it suppresses progesterone levels, LH, and FSH hormone levels.
40 mg or more once per day has been reduces testosterone levels to sustained castrate levels (<20 ng/dL) in men.
It suppresses luteinizing hormone and follicle-stimulating hormone levels in men.
Lower doses of relugolix achieve partial sex hormone suppression in the treatment of endometriosis and uterine fibroids, and reduce the incidence and severity of menopausal symptoms such as hot flushes and decreased bone mineral density that are secondary to estrogen deficiency.
Steady-state levels are reached within 1 week with 40 mg/day dose.
Oral bioavailability of relugolix by about 50%
Plasma protein binding is approximately 68 to 71% over a concentration range of 0.05 to 5 μg/mL.
Its elimination half life is 36 to 65 hours across a dosage range of 20 to 180 mg/day.
It was the second orally active GnRH antagonist to be introduced following elagolix (brand name Orilissa)
Side effects include: menstrual abnormalities, hot flashes, excessive sweating, headache, and decreased bone mineral density.
The most common adverse reactions reported were: hot flushes, musculoskeletal pain, fatigue, diarrhea, and constipation.
The most common laboratory abnormalities were increased glucose, triglyceride, alanine aminotransferase, and aspartate aminotransferase levels.
A dosage of relugolix of 40 mg once per day has been found to suppress estradiol levels to postmenopausal levels (<20 pg/mL) within 24 hours in premenopausal women.
Estradiol levels have been found to return to normal concentrations within 4 weeks of discontinuation of relugolix in premenopausal women.
In pre-menopausal women it suppresses levels of progesterone, luteinizing hormone, and follicle stimulating hormone.
Relugolix at a dosage of 40 mg or more once per day reduces testosterone levels to sustained castrate levels (<20 ng/dL) in men, and also suppresses luteinizing hormone and follicle-stimulating hormone levels.
A single 40-mg oral dose of relugolix has been found to result in peak levels of relugolix of 29 ng/mL (47 nmol/L) after 1.5 hours.
Food ingestion with medication administration diminishes the oral bioavailability of relugolix by about 50%.
Plasma protein binding of relugolix is approximately 68 to 71% over a concentration range of 0.05 to 5 μg/mL.
It has an elimination half-life of is 36 to 65 hours across a dosage range of 20 to 180 mg/day.
83% excreted in the feces, only 4% in urine, and 6% is excreted unchanged.