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GnRH Antagonist (Oral) Pregnancy: Contraindicated in pregnant women. Exposure to Orilissa early in pregnancy may increase the risk of early pregnancy loss. Discontinue Orilissa if pregnancy occurs during treatment. The limited human data are insufficient to determine whether there is a risk for major birth defects or miscarriage (two cases of congenital malformation were reported among 49 pregnancies in clinical trials; no pattern identified). Animal studies: post-implantation loss in rats and spontaneous abortion and total litter loss in rabbits at multiples of the maximum recommended human dose. Exclude pregnancy before starting, and use effective non-hormonal contraception during treatment and for 28 days after discontinuing. This summary may be incomplete — check the full SPC.

Elagolix

Brand names: Orilissa

Elagolix is an orally active gonadotrophin-releasing hormone (GnRH) receptor antagonist used in the management of endometriosis-associated pain.

Adult dose

Dose: Moderate to severe pain associated with endometriosis: 150 mg once daily (initiate at this dose; maximum treatment duration 24 months). Where dyspareunia coexists, consider 200 mg twice daily (maximum treatment duration 6 months).
Route: Oral - once daily at approximately the same time each day, with or without food
Frequency: 150 mg once daily; or 200 mg twice daily where dyspareunia coexists
Source Table 1 (Recommended Dosage and Duration of Use), as retrieved: 'Initiate treatment with ORILISSA 150 mg once daily - 24 months - None [coexisting condition]'; 'Consider initiating treatment with ORILISSA 200 mg twice daily - 6 months - Dyspareunia'; 'Initiate treatment with ORILISSA 150 mg once daily. Use of 200 mg twice daily is not recommended. - 6 months - Moderate hepatic impairment (Child-Pugh Class B)'. Normal liver function or mild hepatic impairment: 150 mg once daily for up to 24 months or 200 mg twice daily for up to 6 months. Moderate hepatic impairment: 150 mg once daily for up to 6 months. Label wording: 'Exclude pregnancy before starting ORILISSA or start ORILISSA within 7 days from the onset of menses.' 'Use the lowest effective dose, taking into account the severity of symptoms and treatment objectives.' 'Limit the duration of use because of bone loss.' Missed dose: take it on the same day as soon as she remembers, then resume the regular schedule; 150 mg once daily - take no more than 1 tablet each day; 200 mg twice daily - take no more than 2 tablets each day. Not established in paediatric patients. The label prints a maximum treatment DURATION per regimen (above) but no separate maximum daily dose, so none is stored. No UK SPC for elagolix is listed on eMC — this dose is from US prescribing information (Orilissa) and must be verified against UK practice.

Dose adjustments

Hepatic

Mild hepatic impairment (Child-Pugh A): no dosage adjustment required. Moderate hepatic impairment (Child-Pugh B; about 3-fold higher elagolix exposure): 150 mg once daily, treatment limited to 6 months; 200 mg twice daily is not recommended. Severe hepatic impairment (Child-Pugh C; about 7-fold higher exposure): contraindicated.

Dose independently re-sourced from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Pregnancy (exposure early in pregnancy may increase the risk of early pregnancy loss)
  • Known osteoporosis (risk of further bone loss)
  • Severe hepatic impairment (Child-Pugh C)
  • Taking inhibitors of organic anion transporting polypeptide (OATP)1B1 that are known or expected to significantly increase elagolix plasma concentrations
  • Known hypersensitivity to Orilissa or any of its inactive components (reactions have included anaphylaxis and angioedema)

Side effects

  • Most common (>5% in clinical trials): hot flushes and night sweats, headache, nausea, insomnia, amenorrhoea, anxiety, arthralgia, depression-related adverse reactions and mood changes
  • Dose- and duration-dependent decrease in bone mineral density that may not be completely reversible
  • Suicidal ideation and behaviour (including one completed suicide in the endometriosis trials) and exacerbation of mood disorders
  • Dose-dependent elevations of serum ALT (at least 3 times the upper limit of the reference range in trials)
  • Reduced menstrual bleeding, which may reduce the ability to recognise pregnancy

Interactions

  • Hormonal contraceptives - use effective non-hormonal contraception during treatment and for 28 days after stopping; 200 mg twice daily with an ethinyl estradiol-containing contraceptive raised ethinyl estradiol 2.2-fold (not recommended); 200 mg twice daily with a combined contraceptive containing 0.1 mg levonorgestrel reduced levonorgestrel by 27%; estrogen-containing contraceptives are expected to reduce elagolix efficacy
  • Strong CYP3A inhibitors - 200 mg twice daily not recommended for more than 1 month; limit 150 mg once daily use with strong CYP3A inhibitors to 6 months
  • Rifampin / strong CYP3A inducers - may decrease elagolix concentrations; 200 mg twice daily with rifampin not recommended; limit 150 mg once daily with rifampin to 6 months
  • OATP1B1 inhibitors that significantly increase elagolix concentrations - contraindicated
  • Digoxin (concentrations increased) - increase monitoring of digoxin concentrations and signs of toxicity when starting or stopping elagolix
  • Oral midazolam (decreased) - consider increasing the midazolam dose by no more than 2-fold, individualised to response
  • Rosuvastatin (decreased) - monitor lipid levels and adjust the rosuvastatin dose if necessary
  • Omeprazole (increased) - no adjustment for omeprazole 40 mg once daily; consider omeprazole dose reduction with higher doses

Monitoring

  • Exclude pregnancy before starting (or start within 7 days of the onset of menses); perform pregnancy testing if pregnancy is suspected and discontinue if confirmed
  • Consider assessment of bone mineral density in patients with a history of low-trauma fracture or other risk factors for osteoporosis or bone loss; limit the duration of use to reduce bone loss
  • Promptly evaluate patients with depressive symptoms, new or worsening depression, anxiety or other mood changes; reassess benefit and risk if suicidal ideation or behaviour occurs
  • Instruct patients to seek medical attention for signs of liver injury such as jaundice; promptly evaluate elevated liver tests to decide whether continued therapy is justified
  • Digoxin concentrations and lipid levels (if on rosuvastatin) when combined with elagolix

Clinical monograph

How it works

It competitively blocks pituitary GnRH receptors, suppressing luteinising hormone and follicle-stimulating hormone release and thereby lowering ovarian oestrogen production to reduce endometriotic activity and pain.

Prescribing in practice

  • Its hypo-oestrogenic effect causes dose-dependent loss of bone mineral density, so duration of use is limited and bone health must be considered, particularly with the higher-exposure regimen.
  • Exclude pregnancy before starting and advise effective non-hormonal contraception, as it is not a contraceptive and can reduce the efficacy of oestrogen-containing contraceptives.
  • Hot flushes and other menopausal-type symptoms are common owing to oestrogen suppression.

Monitoring

Assess and monitor bone mineral density with longer use, and review menopausal-type symptoms, mood and liver-related parameters as clinically indicated.

Counselling the patient

  • Use a reliable non-hormonal contraceptive method, as this medicine is not a contraceptive.
  • Hot flushes, night sweats and mood changes may occur because of lowered oestrogen.
  • Treatment duration is limited to protect your bones, so attend reviews as arranged.

Evidence & guidelines

Elagolix has been evaluated in randomised trials demonstrating reduced dysmenorrhoea and non-menstrual pelvic pain in endometriosis, with dose-dependent reductions in bone mineral density.

Reference: ELARIS EM-I trial (Taylor et al. NEJM 2017); ELARIS EM-II trial; FDA approval 2018; ESHRE Endometriosis Guideline (2022); SPC Orilissa; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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