Consumer medicine information

1. Why am I taking Ryeqo?

Ryeqo contains the active ingredients, relugolix, estradiol hemihydrate and norethisterone acetate. Ryeqo is taken to treat adult women (over the age of 18 years) before they reach menopause for moderate to severe symptoms of uterine fibroids (commonly known as myomas), and for symptomatic treatment of endometriosis in women with a history of previous medical or surgical treatment for their endometriosis.
For more information, see Section 1. Why am I taking Ryeqo? in the full CMI.

2. What should I know before I take Ryeqo?

Do not use if you have ever had an allergic reaction to Ryeqo or any of the ingredients listed at the end of the CMI.
Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.
For more information, see Section 2. What should I know before I take Ryeqo? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Ryeqo and affect how it works.
A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take Ryeqo?

• Take one tablet each day.

• The tablet must be taken orally every day, at about the same time, with or without food with a little liquid.

5. What should I know while taking Ryeqo?

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention. Ask your doctor or pharmacist if you have any further questions about side effects. The most common side effects are headaches, hot flushes, excessive, irregular, or prolonged bleeding from the womb (uterine bleeding), hair loss, decreased interest in sex, irritability, increased sweating, a lump in the breast tissue (breast cyst), indigestion, night sweats, back pain, joint pain, genital area dryness. Serious side effects include uterine myoma expulsion.
For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

1 Name of Medicine

Relugolix, estradiol (as hemihydrate) and norethisterone acetate.

2 Qualitative and Quantitative Composition

Each Ryeqo 40/1/0.4 (Ryeqo) film-coated tablet contains 40 mg relugolix, 1 mg estradiol (as hemihydrate) and 0.5 mg norethisterone acetate.
Each film-coated tablet contains approximately 80 mg of lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Film-coated tablet.
Light yellow to yellow, round film-coated tablet of 8 mm with "415" on one side and plain-faced on the other side.

4 Clinical Particulars

4.9 Overdose

Single doses of relugolix up to 360 mg (9 times the recommended clinical dose of 40 mg) have been administered to healthy men and women and were generally well tolerated.
Overdoses up to 2 times the recommended dose have been reported during the clinical development of relugolix in combination with estradiol and norethisterone acetate without reports of adverse events.
Supportive care is recommended if an overdose occurs. The amount of relugolix, estradiol or norethisterone removed by haemodialysis is unknown.
Serious ill effects have not been reported following acute ingestion of large doses of estrogen containing drug products by young children. Overdose of estradiol and norethisterone acetate may cause nausea and vomiting, and withdrawal bleeding may occur in women.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Non-clinical studies have not been conducted with relugolix in combination with estradiol and norethisterone acetate.
Genotoxicity. Relugolix was not mutagenic in the in vitro bacterial reverse mutation (Ames) assay or clastogenic in the in vitro chromosomal aberration assay in Chinese hamster lung cells or the in vivo rat bone marrow micronucleus assay.
There is limited evidence available in the literature suggesting that estradiol may be weakly genotoxic at high doses. No evidence could be found for an increase in the rate of gene mutation in bacterial or mammalian cells, but there was some evidence for the induction of chromosomal aberrations and aneuploidy in mammalian cells, and two groups reported an increase in the incidence of sister chromatid exchanges, indicative of DNA damage. Neither of these latter effects were induced by estradiol in human lymphocyte cultures. Importantly, there was no evidence for increased micronuclei formation in well controlled rodent bone marrow assays.
Carcinogenicity. Relugolix was not carcinogenic in mice at oral doses up to 100 mg/kg/day or rats at oral doses up to 600 mg/kg/day, with exposures in both species higher than 250 times the human exposure at the recommended clinical dose of 40 mg daily, based on AUC. Since the binding affinity of relugolix for GnRH receptors in rats is more than 1000-fold less than in humans, the rat model only addressed the carcinogenic potential of any off-target effects of relugolix and its metabolites (and not malignancies arising from the pharmacodynamic effect of relugolix).
Supra-physiological doses of estradiol have been associated with the induction of tumours in estrogen-dependent target organs in all rodent species tested. The relevance of these findings with respect to humans has not been established.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Chemical structure. Relugolix.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSRELUGO.gif Estradiol hemihydrate.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSESTHEM.gif Norethisterone acetate.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSNORETH.gif CAS number. Relugolix. 737789-87-6.
Estradiol hemihydrate. 35380-71-3.
Norethisterone acetate. 51-98-9.

7 Medicine Schedule (Poisons Standard)

(Schedule 4) Prescription Only Medicine.

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/RYEQO0ST.gif