Usage
Elagolix is prescribed for the management of moderate to severe pain associated with endometriosis. It belongs to the pharmacological class of gonadotropin-releasing hormone (GnRH) receptor antagonists. Elagolix works by binding to and blocking the GnRH receptors in the pituitary gland. This action suppresses the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), ultimately reducing estrogen production and partially suppressing ovarian activity. This hormonal suppression helps alleviate endometriosis-related pain.
Alternate Names
Elagolix sodium is the name of the sodium salt form. Orilissa is a popular brand name for Elagolix. There are currently no widely used international or regional variations of the name Elagolix.
How It Works
Pharmacodynamics: Elagolix suppresses the hypothalamic-pituitary-gonadal (HPG) axis by competitively binding to GnRH receptors in the pituitary gland. This inhibits the release of LH and FSH, reducing ovarian hormone production (primarily estradiol and progesterone), leading to a hypoestrogenic state. This state helps manage endometriosis-related pain by reducing endometrial implants and associated inflammation.
Pharmacokinetics:
- Absorption: Elagolix is rapidly absorbed after oral administration, reaching peak plasma concentrations within 1 to 2 hours. Food does not significantly affect absorption.
- Metabolism: Elagolix is primarily metabolized by the liver via CYP3A4 enzyme. It is also a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1 and 1B3 transporters.
- Elimination: Elagolix is eliminated primarily through hepatic metabolism, with a small portion excreted unchanged in the urine and feces. Its elimination half-life is approximately 4 to 6 hours.
Mode of Action: Elagolix acts as a competitive antagonist at GnRH receptors. It directly blocks the binding of endogenous GnRH to its receptors in the pituitary gonadotrophs, thereby preventing the release of gonadotropins, LH, and FSH.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Elagolix exerts its effects through competitive antagonism of GnRH receptors. It is a weak to moderate inducer of CYP3A4. It is a substrate of OATP1B1 and a weak inhibitor of OATP1B3.
Elimination Pathways: Elagolix is eliminated mainly by hepatic metabolism, predominantly through CYP3A4-mediated oxidation. Excretion of unchanged drug in urine and feces are minor pathways.
Dosage
Standard Dosage
Adults:
- 150 mg orally once daily for up to 24 months.
- 200 mg orally twice daily for up to 6 months (for patients with dyspareunia).
Children: The safety and efficacy of Elagolix have not been established in pediatric patients.
Special Cases:
- Elderly Patients: No specific dose adjustments are recommended for elderly patients. However, clinical experience in this population is limited. Monitor for adverse effects and adjust the dose as needed.
- Patients with Renal Impairment: No dose adjustment is necessary for patients with renal impairment.
- Patients with Hepatic Dysfunction:
- Mild hepatic impairment (Child-Pugh A): No dose adjustment required.
- Moderate hepatic impairment (Child-Pugh B): 150 mg orally once daily for up to 6 months. The 200 mg twice-daily regimen is not recommended.
- Severe hepatic impairment (Child-Pugh C): Elagolix is contraindicated.
- Patients with Comorbid Conditions: Monitor closely and consider dose adjustments for patients with osteoporosis, depression, or anxiety, and those using medications that interact with Elagolix (e.g., strong OATP1B1 inhibitors).
Clinical Use Cases
Elagolix is specifically indicated for the management of endometriosis-associated pain and is not currently indicated for use in settings like intubation, surgical procedures, mechanical ventilation, intensive care, or emergency situations.
Dosage Adjustments
Dose modifications may be necessary based on individual patient response, tolerability, and coexisting conditions. Dose adjustment recommendations for hepatic impairment are detailed above. Concomitant use with strong OATP1B1 inhibitors is contraindicated. For strong CYP3A inhibitors, the 150 mg once-daily regimen should be limited to 6 months.
Side Effects
Common Side Effects:
Hot flashes, night sweats, headache, nausea, difficulty sleeping, absence of menstrual periods (amenorrhea), irregular menstrual bleeding, anxiety, joint pain, depression, mood changes.
Rare but Serious Side Effects:
Osteoporosis (bone loss), increased risk of suicidal thoughts and behavior, hepatic dysfunction (including elevated liver enzymes and jaundice).
Long-Term Effects:
Prolonged use of Elagolix can cause significant bone loss. Bone mineral density should be monitored regularly.
Adverse Drug Reactions (ADR):
Anaphylaxis, angioedema, hepatotoxicity, severe depression or suicidal ideation.
Contraindications
- Pregnancy
- Known osteoporosis
- Severe hepatic impairment (Child-Pugh C)
- Concomitant use of strong OATP1B1 inhibitors (e.g., cyclosporine, gemfibrozil)
- Hypersensitivity to Elagolix or any component of the formulation
Drug Interactions
- Hormonal Contraceptives: Elagolix may reduce the effectiveness of estrogen-containing contraceptives. Non-hormonal contraception is recommended.
- Strong OATP1B1 Inhibitors: Concomitant use is contraindicated (e.g., cyclosporine, gemfibrozil).
- CYP3A4 Inducers (e.g., rifampin): May reduce the effectiveness of Elagolix.
- CYP3A4 Substrates (e.g., midazolam): Elagolix may decrease the levels of some CYP3A4 substrates. Monitor and adjust the substrate dose as needed.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: X. Elagolix is contraindicated in pregnancy. It can increase the risk of early pregnancy loss.
- Breastfeeding: It is unknown if Elagolix passes into breast milk. Due to the potential for adverse effects on the infant, breastfeeding is not recommended while taking Elagolix.
Drug Profile Summary
- Mechanism of Action: GnRH receptor antagonist, suppressing pituitary gonadotropin release and reducing estrogen production.
- Side Effects: Hot flashes, night sweats, headache, nausea, insomnia, amenorrhea, irregular bleeding, anxiety, joint pain, depression, mood changes. Serious side effects: Osteoporosis, suicidal ideation/behavior, hepatotoxicity.
- Contraindications: Pregnancy, osteoporosis, severe hepatic impairment, strong OATP1B1 inhibitors, hypersensitivity.
- Drug Interactions: Hormonal contraceptives, strong OATP1B1 inhibitors, CYP3A4 inducers/substrates.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy. Breastfeeding is not recommended.
- Dosage: Adults: 150 mg once daily or 200 mg twice daily (max. 6 months for 200 mg BID).
- Monitoring Parameters: Liver function tests, bone mineral density, mood changes, suicidal ideation.
Popular Combinations
Elagolix is typically used as monotherapy. Supplemental calcium and vitamin D are often recommended to mitigate the risk of bone loss.
Precautions
- General Precautions: Assess bone mineral density and liver function prior to and during treatment. Evaluate for mental health conditions. Exclude pregnancy before starting therapy.
- Specific Populations:
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Not recommended.
- Children & Elderly: Safety and efficacy not established in children. Use with caution in the elderly.
- Menstruating Individuals: Monitor menstrual cycle changes. Use reliable non-hormonal contraception.
- Lifestyle Considerations: Advise patients about potential effects on mood and the importance of reporting any changes in mood or behavior.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Elagolix?
A: 150 mg once daily for up to 24 months, or 200 mg twice daily for up to 6 months (for patients with dyspareunia).
Q2: How does Elagolix work?
A: It is a GnRH receptor antagonist, suppressing the release of LH and FSH, leading to decreased estrogen production.
Q3: What are the most common side effects of Elagolix?
A: Hot flashes, night sweats, headache, nausea, difficulty sleeping, amenorrhea/irregular bleeding, anxiety, joint pain, depression, mood changes.
Q4: Is Elagolix safe to use during pregnancy?
A: No, Elagolix is contraindicated in pregnancy due to the risk of early pregnancy loss.
Q5: Can Elagolix be used while breastfeeding?
A: Breastfeeding is not recommended while taking Elagolix. It is not known whether Elagolix passes into breast milk.
Q6: What are the contraindications for using Elagolix?
A: Pregnancy, known osteoporosis, severe hepatic impairment, concomitant use of strong OATP1B1 inhibitors, hypersensitivity to Elagolix.
Q7: Does Elagolix interact with other medications?
A: Yes. Clinically significant interactions can occur with hormonal contraceptives, strong OATP1B1 inhibitors, and CYP3A4 inducers/substrates.
Q8: How should bone health be managed in patients taking Elagolix?
A: Monitor bone mineral density before and during treatment. Calcium and vitamin D supplementation are often recommended.
Q9: What should be done if a patient misses a dose of Elagolix?
A: Take the missed dose as soon as remembered on the same day. Do not double the next dose. Resume the regular dosing schedule.
Q10: What are the long-term effects of Elagolix use?
A: The most significant long-term effect is decreased bone mineral density (bone loss), which can increase the risk of fractures with prolonged use. Regular monitoring of bone mineral density is essential.
