estradiol hemihydrate + norethisterone acetate + relugolix: clinical use

Prescribing considerations

• Initiation and supervision should be by a clinician experienced in uterine fibroids or endometriosis.
• Exclude pregnancy, stop hormonal contraception and review personal and family thrombotic history before initiation.
• Assess blood pressure, osteoporosis and fracture risks, migraine, depression, liver disease, unexplained bleeding and sex-steroid-sensitive malignancy.
• Discuss expected bleeding changes, rapid return of ovulation after discontinuation and symptoms requiring urgent assessment.

Contraindications and cautions

• Past or current venous or arterial thromboembolism, or known thrombophilia
• Known osteoporosis
• Migraine with aura or headache with focal neurological symptoms
• Known or suspected sex-steroid-sensitive malignancy
• Current or previous liver tumour, or severe liver disease before liver tests normalise
• Pregnancy, suspected pregnancy or breastfeeding
• Genital bleeding of unknown cause
• Concomitant hormonal contraception
• Hypersensitivity to an active ingredient or excipient

Monitoring

• Measure blood pressure and perform clinically indicated examination before treatment; undertake periodic reviews.
• Consider baseline DXA where bone-loss risk factors exist and repeat DXA during longer-term treatment as specified in the product information.
• Review persistent excessive bleeding, recurrent severe bleeding after initial improvement, mood deterioration, jaundice or clinically significant hypertension.
• Account for possible effects on liver, thyroid, adrenal, renal, metabolic and coagulation laboratory tests.

Clinical pharmacology

Relugolix competitively antagonises pituitary GnRH receptors, reducing LH and FSH and suppressing follicular development, ovulation and ovarian steroid production. Estradiol provides add-back replacement to reduce low-oestrogen effects; norethisterone acetate opposes oestrogen-driven endometrial proliferation.

Formulation and product differences

• It is a single oral film-coated combination tablet.
• The tablet is light yellow to yellow, round and marked “415” on one face.
• It contains lactose monohydrate and is unsuitable for certain rare hereditary disorders of carbohydrate absorption.

Tablet

Route: Oral

Strengths: 40 mg + 1 mg + 0.5 mg