RYEQO

What it is

Ryeqo is a film-coated tablet containing 40 mg relugolix, 1 mg estradiol (as hemihydrate) and 0.5 mg norethisterone acetate. Relugolix is a non-peptide gonadotropin-releasing hormone (GnRH) receptor antagonist that binds to and inhibits GnRH receptors in the anterior pituitary gland. Estradiol is the same as the endogenously produced hormone and is a potent agonist of the nuclear estrogen receptor subtypes, while norethisterone acetate is a synthetic progestogen. This medicinal product is subject to additional monitoring in Australia.

Approved indications

Ryeqo is indicated in adult women of reproductive age for: — Treatment of moderate to severe symptoms of uterine fibroids. — Symptomatic treatment of endometriosis in women with a history of previous medical or surgical treatment for their endometriosis.

Dosing overview

One tablet of Ryeqo must be taken once daily, at about the same time with or without food. When starting treatment, the first tablet must be taken within 5 days of the onset of menstrual bleeding; if treatment is initiated on another day of the menstrual cycle, irregular and/or heavy bleeding may initially occur. Use is recommended to be limited to 24 months, with extension of therapy conditional on stability of bone mineral density assessment and reassessment of risk/benefit in the individual patient by the treating physician.

Key safety warnings

The use of medicinal products containing an estrogen and a progestogen increases the risk of arterial or venous thromboembolism compared with no use, although the risk of arterial or venous thromboembolism with Ryeqo has not been established. Ryeqo contains doses of estrogen and progestogen lower than those used in combined hormonal contraceptives and are provided in combination with relugolix, a GnRH receptor antagonist that suppresses ovarian production of estrogen and progesterone. Ryeqo is contraindicated in women with past or present venous or arterial thromboembolic disease. In some women treated with Ryeqo who had normal bone mineral density at start of treatment, a bone loss varying from >3–8% was reported. Following an initial non-clinically relevant decrease in bone mineral density, it stabilised after 12–24 weeks of treatment and thereafter remained stable as measured up to 2 years. The mean decrease in bone mineral density during the first year of treatment with Ryeqo was 0.69%, however, decreases of >3% were seen in 21% of patients. A DXA scan is recommended at baseline, after the first 52 weeks of treatment, and annually thereafter. Gonadotropin-releasing hormone receptor antagonists, including Ryeqo, have been associated with mood disorders (including depression) and suicidal ideation. Women with a history of suicidal ideation, depression and mood disorders should be evaluated prior to initiating treatment. Women must be advised to contact their physician in case of mood changes and depressive symptoms, including shortly after initiating the treatment. Ryeqo should be discontinued if depression recurs to a serious degree. Women who take Ryeqo commonly experience amenorrhoea or a reduction in the amount, intensity, or duration of menstrual bleeding. This change in menstrual bleeding pattern may reduce the ability to recognise the occurrence of a pregnancy in a timely manner. Pregnancy testing should be performed if pregnancy is suspected and treatment discontinued if pregnancy is confirmed.

Contraindications

Ryeqo is contraindicated in women with hypersensitivity to the active substances or excipients; venous thromboembolic disorder, past or present (such as deep venous thrombosis or pulmonary embolism); arterial thromboembolic cardiovascular disease, past or present (such as myocardial infarction, cerebrovascular accident, ischaemic heart disease); known thrombophilic disorders (such as protein C, protein S or antithrombin deficiency or activated protein C resistance, including Factor V Leiden); known osteoporosis; headaches with focal neurological symptoms or migraine headaches with aura; known or suspected sex steroid-influenced malignancies (such as of the genital organs or the breasts); presence or history of liver tumours (benign or malignant); presence or history of severe hepatic disease as long as liver function values have not returned to normal; pregnancy or suspected pregnancy and breastfeeding; genital bleeding of unknown aetiology; and concomitant use of hormonal contraceptives.

PBS listing

PBS listing information for Ryeqo is not available in the provided source documents.

Regulatory history

Ryeqo 40/1/0.5 was first listed on the ARTG on 6 September 2022. The PBAC recommended Ryeqo for endometriosis (moderate to severe pain) in March 2024. In November 2024, the PBAC provided advice that did not revise the March 2024 recommendation, noting that the submission did not provide sufficient justification for proposed financial estimates and risk-sharing arrangement, and that proposed estimates appeared substantially overestimated. The PBAC recommended an additional clinical criterion to limit treatment to a lifetime maximum of 24 months.