ELAGOLIX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ELAGOLIX (ELAGOLIX).
Gonadotropin-releasing hormone (GnRH) receptor antagonist that competitively binds to GnRH receptors in the anterior pituitary, reducing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release, thereby suppressing ovarian estradiol production.
| Metabolism | Primarily metabolized by CYP3A4; minor contribution from CYP2D6 and CYP2C8. |
| Excretion | Renal (approximately 70% as unchanged drug and metabolites), fecal (approximately 30%) |
| Half-life | Terminal elimination half-life is approximately 4–6 hours. Clinical context: Steady state achieved within 5 days; tid dosing maintains therapeutic concentrations. |
| Protein binding | Approximately 99% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | Vd/F is approximately 40–60 L (0.5–0.8 L/kg). Clinical meaning: Extensive tissue distribution, consistent with a large volume of distribution. |
| Bioavailability | Oral: Approximately 30% (low due to first-pass metabolism); food increases exposure by approximately 30%. |
| Onset of Action | Oral: Inhibition of ovulation and reduction of estradiol levels are evident within 1 day; peak plasma concentration at 1–2 hours post-dose. |
| Duration of Action | Estradiol suppression persists for at least 8 hours after a single dose, allowing tid dosing; complete recovery of estradiol levels occurs within 2–4 days after discontinuation. |
200 mg orally twice daily
| Dosage form | TABLET |
| Renal impairment | eGFR 30-89 mL/min: no adjustment. eGFR 15-29 mL/min: 100 mg twice daily. eGFR <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 100 mg twice daily. Child-Pugh C: not recommended. |
| Pediatric use | Not established; safety and efficacy in pediatric patients have not been studied. |
| Geriatric use | No specific dose adjustment required; clinical studies included limited patients ≥65 years, but no differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ELAGOLIX (ELAGOLIX).
| Breastfeeding | Elagolix is excreted in animal milk; no human data. M/P ratio unknown. Not recommended during breastfeeding. |
| Teratogenic Risk | First trimester: High risk of pregnancy loss and major birth defects based on animal data and mechanism of action. Second and third trimesters: Contraindicated due to potential for harm. Elagolix is contraindicated in pregnancy. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to elagolix or any excipients","Concomitant use with strong organic anion-transporting polypeptide (OATP) 1B1 inhibitors (e.g., cyclosporine, gemfibrozil)","Pregnancy, or women of reproductive potential not using effective contraception","Existing osteoporosis or severe bone loss","History of suicidal ideation or behavior"]
| Precautions | ["Hepatic transaminase elevations: monitor liver function before and during treatment; discontinue if elevation >3x ULN or if signs of liver injury occur.","Bone density loss: monitor bone mineral density with long-term use; consider additional calcium/vitamin D.","Mood changes: increased risk of depression, suicidal ideation; monitor for new or worsening symptoms.","Altered menstrual bleeding; exclude pregnancy before starting.","Risk of osteoporosis with prolonged use."] |
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| Pregnancy testing required before initiation, monthly during treatment, and one month after discontinuation. No fetal monitoring is indicated as drug is contraindicated. |
| Fertility Effects | Reversible suppression of ovulation; intended effect for endometriosis. Return to ovulation may be delayed after discontinuation. |