ELAGOLIX
Clinical safety rating
cautionComprehensive clinical and safety monograph for ELAGOLIX (ELAGOLIX).
Comprehensive clinical and safety monograph for ELAGOLIX (ELAGOLIX).
Management of moderate to severe pain associated with endometriosis
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. |
| Molecular Weight | 567.53 |
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 | Based on animal studies and mechanism of action, elagolix may cause fetal harm. Avoid use in pregnancy; rule out pregnancy before initiation. |
| 2nd trimester | Based on animal studies and mechanism of action, elagolix may cause fetal harm. Avoid use in pregnancy. |
| 3rd trimester | Based on animal studies and mechanism of action, elagolix may cause fetal harm. Avoid use in pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for ELAGOLIX (ELAGOLIX).
| Placental transfer | Expected to cross placenta based on molecular weight and animal studies showing fetal exposure. |
| Breastfeeding | No human data on excretion in breast milk; potential for serious adverse reactions in nursing infants. Advise against breastfeeding during therapy and for 1 week after last dose. |
| Lactation Rating | L5 |
| 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 | 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Known hypersensitivity to elagolix or any componentConcomitant use with strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin)Concomitant use with strong organic anion transporting polypeptide (OATP) 1B1 inhibitors (e.g., rifampin)Concomitant use with strong CYP3A inducers (e.g., carbamazepine, rifampin) reduces efficacyPre-existing osteoporosis or bone density lossPregnancyCurrent or history of suicidal thoughts or actions
| 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. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they inhibit CYP3A4 and may increase elagolix levels. No other food restrictions. |
| Clinical Pearls | Elagolix is an oral GnRH antagonist for endometriosis-associated pain. Monitor bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA) if using >12 months or in patients with osteoporosis risk. Avoid use with strong CYP3A inducers (e.g., rifampin) or inhibitors (e.g., ketoconazole). May reduce efficacy of hormonal contraceptives. Assess pregnancy status before starting due to teratogenicity. |
| Patient Advice | Take elagolix at the same time daily with or without food. · Avoid grapefruit or grapefruit juice during treatment. · Use non-hormonal contraception (e.g., condoms) because elagolix may reduce hormonal contraceptive effectiveness. · Report severe headaches, vision changes, or heavy bleeding promptly. · Do not take elagolix if pregnant or planning to become pregnant; use effective birth control. |
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