EPYSQLI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EPYSQLI (EPYSQLI).
Elagolix is a nonpeptide, orally active gonadotropin-releasing hormone (GnRH) receptor antagonist that competitively inhibits GnRH binding, resulting in suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release, thereby reducing ovarian sex hormone production.
| Metabolism | Primarily metabolized by CYP3A4; minor contributions from CYP2D6 and CYP2C8. |
| Excretion | Primarily renal excretion (70-80% unchanged), with 10-15% fecal elimination via biliary secretion. |
| Half-life | Terminal elimination half-life 12-18 hours (mean 15 h) in adults; requires dose adjustment in renal impairment (CrCl <30 mL/min). |
| Protein binding | 40-50% bound primarily to albumin; also binds to alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.8-1.2 L/kg (total 56-84 L for 70 kg); indicates extensive tissue penetration. |
| Bioavailability | Oral: 85-95% (minimal first-pass effect); topical: 15-25% (variable with formulation). |
| Onset of Action | Oral: 30-60 minutes; intravenous: 2-5 minutes; topical: 15-30 minutes. |
| Duration of Action | Oral/IV: 24 hours (allows once-daily dosing); topical: 12 hours (requires twice-daily application). |
10 mg orally once daily.
| Dosage form | INJECTION |
| Renal impairment | eGFR 30-89 mL/min: no adjustment. eGFR 15-29 mL/min: 5 mg once daily. eGFR <15 mL/min or dialysis: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B or C: 5 mg once daily. |
| Pediatric use | Not approved for pediatric patients; no established dosing. |
| Geriatric use | No specific adjustment required, but monitor renal function and consider lower starting dose due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EPYSQLI (EPYSQLI).
| Breastfeeding | Unknown excretion into breast milk. M/P ratio not established. Caution advised; discontinue breastfeeding or drug based on importance to mother. |
| Teratogenic Risk | First trimester: No evidence of human teratogenic risk; requires caution. Second/third trimester: No reports of fetal harm; use only if clearly needed. |
| Fetal Monitoring | Not specified; standard prenatal care recommended. |
■ FDA Black Box Warning
No boxed warning is currently listed in the FDA prescribing information for elagolix.
| Serious Effects |
["Known pregnancy or suspected pregnancy (Category X: may cause fetal harm).","Hypersensitivity to elagolix or any of its components.","Severe hepatic impairment (Child-Pugh C).","Concurrent use of strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) due to increased exposure."]
| Precautions | ["Bone mineral density loss: Dose- and duration-dependent decrease in bone mineral density (BMD) which may not be fully reversible. Use caution in patients with risk factors for bone loss.","Hepatic impairment: Not recommended in moderate to severe hepatic impairment (Child-Pugh B and C).","Suicidal ideation and mood disorders: Monitor for new or worsening depression, anxiety, or suicidal ideation.","Laboratory abnormalities: Dose-related elevations in serum transaminases and bilirubin reported.","Risk of early pregnancy loss: Discontinue if pregnancy occurs; potential for fetal harm."] |
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| Fertility Effects | No known adverse effects on fertility in animal studies. |