Generic Name

Elagolix

Mechanism

Elagolix is a non‑peptide, oral GnRH (gonadotropin‑releasing hormone) antagonist.
• Competitive inhibition at the GnRH receptor on the pituitary gland blocks the release of LH (luteinizing hormone) and FSH (follicle‑stimulating hormone).
• Resulting hypoestrogenicity reduces endometrial stimulation and uterine fibroid growth.
• The effect is rapid, reversible, and does not rely on receptor desensitization (unlike GnRH agonists).

Pharmacokinetics

• Absorption: Rapid oral absorption; peak plasma concentration (*Cmax*) reached in 0.5–2 h.
• Bioavailability: ~53 % (dose‑dependent, reduced when taken with food).
• Distribution: High plasma protein binding (~99 %).
• Metabolism: Predominantly hepatic, mainly via CYP3A4 and to a lesser extent CYP2D6.
• Elimination: Renal and biliary routes; elimination half‑life ≈4–5 h.
• Drug interactions: Potentiated by strong CYP3A4 inducers (e.g., rifampin); decreased concentrations with strong CYP3A4 inhibitors (e.g., ketoconazole).

Indications

• Endometriosis‑related pelvic pain (moderate to severe) in reproductive‑age women.
• Uterine fibroids (symptomatic uterine bleeding or bulk symptoms) when paired with add‑back therapy.

Contraindications

• Contraindications:
• Known hypersensitivity to elagolix or its excipients.
• Pregnancy or lactation.
• Severe hepatic impairment (Child‑Pugh B/C).
• Warnings:
• Hypoestrogenic side effects: bone mineral density loss, vasomotor symptoms, hot flashes.
• Consideration in estrogen‑dependent tumors (breast, endometrial).
• Potential cardiovascular effects (elevated triglycerides, LDL, blood pressure in some patients).

Dosing

• Take with food to enhance absorption (especially for the 200 mg dose).
• Steady‑state achieved ~14 days.
• Discontinuation: Rapid return of endogenous gonadotropin‑estradiol axis activity; monitor for flare of symptoms.

Adverse Effects

• Common (≥10 %):
• Hot flashes, flushing
• Nausea, vomiting
• Headache, dizziness
• Violation of upper‑limb (liver enzymes↑)
• Fatigue
• Serious (≤1 %):
• Hypersensitivity reactions (rash, angioedema)
• Osteoporosis‑related fractures (with prolonged use without add‑back)
• Severe hepatic injury (rare)
• CV events (elevated lipids, hypertension)

Monitoring

• Bone health: Dual‑energy X‑ray absorptiometry (DEXA) at baseline, 12 mo, then annually if >3 years.
• Liver function tests: ALT/AST at baseline, 1 mo, then 3 mo.
• Lipid panel: Baseline, 3 mo, then annually.
• Pregnancy test: Prior to initiation, then regularly during therapy.
• Contraception counseling (due to risk of fetal harm).

Clinical Pearls

• Add‑back therapy is key: Avoid cumulative bone loss and hot flashes; choose formulation based on patient preference and safety profile.
• Short‑term use for acute flare (≤2 weeks) may relieve severe pain without long‑term risks.
• Use caution in patients with pre‑existing osteopenia – consider baseline DEXA and early add‑back.
• Non‑pregnant female patients: Discuss fertility implications; elagolix does not affect ovarian reserve beyond the hypoestrogenic window.
• Drug‑drug interaction pearls: Check for CYP3A4 inducers (e.g., phenytoin, carbamazepine) that can lower elagolix levels; similarly, potent inhibitors can raise systemic exposure and side‑effect risk.

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• References

Key clinical trials: REPOSE 1 & 2 (endometriosis), AMBITION (fibroids).

FDA prescribing information (2023).

Clinical pharmacology reviews in *Obstetrics & Gynecology* and *Pharmacologic Reports*.