GnRH Antagonist (Oral) Pregnancy: CONTRAINDICATED — non-hormonal contraception required during treatment

Elagolix

Brand names: Orilissa

Adult dose

Dose: Moderate endometriosis pain: 150 mg once daily (up to 24 months); Moderate-severe dyspareunia: 200 mg twice daily (up to 6 months)

Route: Oral

Frequency: Once or twice daily (dose-dependent)

Max: 400 mg/day

Partial oestrogen suppression at 150 mg OD vs near-complete at 200 mg BD; higher dose associated with greater bone loss; no initial flare (immediate onset unlike GnRH agonists)

Paediatric dose

Dose: Not established N/A/kg

Route: N/A

Frequency: N/A

Max: N/A

Not licensed in paediatrics

Dose adjustments

Renal

No dose adjustment required

Hepatic

Moderate hepatic impairment: reduce to 150 mg OD; severe: contraindicated

Paediatric weight-based calculator

Patient weight (kg)

Not licensed in paediatrics

Clinical pearls

ELARIS EM-I and EM-II trials (Taylor et al. NEJM 2017): elagolix significantly reduced dysmenorrhoea and non-menstrual pelvic pain vs placebo in endometriosis — response dose-dependent; 200 mg BD achieved greater pain reduction but more bone loss
Key advantage over GnRH agonists: no initial flare — elagolix provides immediate oestrogen suppression by competitive GnRH receptor blockade; immediate pain relief from day 1 of treatment, important for clinical management
Bone density monitoring: DEXA at baseline if additional risk factors; 200 mg BD limited to 6 months due to cumulative BMD loss; 150 mg OD can be used up to 24 months — dose selection should account for individual BMD risk
Oral non-peptide GnRH antagonist — first in class oral GnRH antagonist for endometriosis in women; replaced need for injectable GnRH agonists in some patients
Pregnancy prevention: non-hormonal contraception required (elagolix reduces oestrogen but does not reliably prevent ovulation at 150 mg OD dose); pregnancy test required before starting

Contraindications

Pregnancy
Severe hepatic impairment
Osteoporosis
Known hypersensitivity

Side effects

Hot flushes/night sweats
Headache
Nausea
Insomnia
Bone mineral density loss (dose and duration dependent)
Mood changes/depression
Amenorrhoea
Hyperlipidaemia

Interactions

Strong CYP3A4 inducers (rifampicin) — significantly reduce elagolix levels; avoid
P-gp inhibitors (ciclosporin, verapamil) — may increase elagolix exposure
Organic anion transporter inhibitors — reduced clearance

Monitoring

BMD (DEXA if >6 months treatment or additional risk factors)
Liver function tests
Lipid profile
Mood and mental health assessment
Pregnancy test before treatment

Reference: BNFc; BNF 90; ELARIS EM-I trial (Taylor et al. NEJM 2017); ELARIS EM-II trial; FDA approval 2018; ESHRE Endometriosis Guideline (2022); SPC Orilissa. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators