Introduction
Elagolix is an orally active gonadotropin-releasing hormone (GnRH) receptor antagonist used for the management of moderate to severe pain associated with endometriosis. By suppressing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), it reduces estrogen production, helping to relieve endometriosis-related pain.
Elagolix has also been studied for the treatment of uterine fibroids and heavy menstrual bleeding. Its oral administration provides a non-surgical treatment option for women with hormone-dependent gynecologic conditions.
Uses
Elagolix is a gonadotropin releasing hormone receptor antagonist used to treat moderate to severe pain in endometriosis.
Elagolix is a gonadotropin-releasing hormone (GnRH) receptor antagonist indicated for the management of moderate to severe pain associated with endometriosis .
Associated Conditions
Pharmacodynamics
During a three menstrual cycle study in healthy women, an elagolix 150 mg once daily regimen and a 200 mg twice daily regimen resulted in an ovulation rate of about 50% and 32%, respectively . In Phase 3 trials in women with endometriosis, elagolix caused a dose-dependent reduction in median estradiol concentrations to approximately 42 pg/mL for the 150 mg once daily regimen and 12 pg/mL for the 200 mg twice daily regimen .
Furthermore, the effect of elagolix on the QTc interval was investigated in a randomized, placebo- and positive-controlled, open-label, single-dose, crossover thorough QTc study in 48 healthy adult premenopausal women . Elagolix concentrations in subjects administered a single dose of 1200 mg was seventeen times higher than the concentration in subjects given elagolix 200 mg twice daily. Nevertheless, there was no clinically relevant prolongation of the QTc interval .
Mechanism of Action
Endometriosis develops when tissue that is similar to the kind that is normally located in the uterus starts to grow outside of the uterus . Such growth leads to various symptoms like pain during periods, pelvic pain between periods, and pain during sexual intercourse . The growths themselves are referred to as lesions and frequently develop on the ovaries, fallopian tubes, and other areas around the uterus, including the bowel or bladder . The growth of these lesions is dependent upon the estrogen hormone .
Elagolix is an orally-administered, nonpeptide small molecule gonadotropin-releasing hormone (GnRH) receptor antagonist that inhibits endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland . Administration of elagolix results in dose-dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased blood concentrations of the ovarian sex hormones, estradiol and progesterone.
Absorption
The Tmax of elagolix is reported as being 1.0 hours . The effect of a high-fat meal (relative to fasting) can result in a reduction of the AUC and Cmax by as much as 24% and 36%, respectively .
Volume of Distribution
The apparent volume of distribution at steady state (Vdss/F) of elagolix is reported to be 1674 for a 150 mg daily regimen and 881 for a 200 mg twice daily regimen .
Protein Binding
The percentage bound to human plasma proteins for elagolix has been documented as 80% .
Route of Elimination
The primary route of elimination of elagolix is via hepatic metabolism .
Half Life
The terminal phase elimination half-life of elagolix is recorded as being 4 to 6 hours .
Clearance
The oral clearance (CL/F) of elagolix is 123 L/hr for a 150 mg once daily regimen and 144 L/hr for a 200 mg twice daily regimen .
Toxicity
In case of overdose, monitor the patient for any signs or symptoms of adverse reactions and initiate appropriate symptomatic treatment, as needed . Common adverse reactions of elagolix include hot flush, headache, nausea, insomnia, mood alterations, amenorrhea, depression, anxiety, arthralgia, bone loss, changes in menstrual bleeding patterns, suicidal ideation and behavior, exacerbation of existing mood disorders, and/or hepatic transaminase elevations .
The recommended duration of use for elagolix is up to 24 months for the 150 mg once daily dose and up to six months for the 200 mg twice daily dose, as it causes a dose-dependent decrease in bone mineral density (BMD) . BMD loss is greater with increasing duration of use and may not be completely reversible after stopping treatment . For women with moderate hepatic impairment, the recommended dosage is 150 mg once daily for up to six months .
Food Interactions
- Administer calcium supplement. This will minimize the risk of bone mineral density loss.
- Administer vitamin supplements. Administer Vitamin D supplements to minimize the risk of bone mineral density loss.
- Take at the same time every day.
- Take with or without food.
Dosage
Initial treatment with Elagolix 150 mg: 150 mg once daily up to 24 months. But in case of moderate hepatic impairment up to 6 months.
Initial treatment with Elagolix 200 mg: 200 mg twice daily up to 6 months (with coexisting dyspareunia). Treatment with Elagolix 200 mg should not exist more than 6 months as it may decrease bone mineral density (BMD).
In moderate to severe hepatic impairment: Elagolix 200 mg is not recommended.
Use in children and adolescents: <18 years not established.
