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Relugolix with estradiol and norethisterone oral


Oral formulations containing relugolix, estradiol and norethisterone.

Drugs List

  • relugolix 40mg and estradiol 1mg and norethisterone 0.5mg tablets
  • RYEQO 40mg+1mg+0.5mg tablets
  • Therapeutic Indications


    Uterine fibroids

    Treatment of moderate to severe symptoms caused by uterine fibroids, in adult women of childbearing age.


    Hormonal contraceptives must be discontinued before commencing therapy with relugolix with estradiol and norethisterone.

    At treatment initiation, the first tablet must be taken within 5 days of the onset of menstrual bleeding. Irregular/heavy bleeding may occur if treatment is initiated on another day in the menstrual cycle.


    One tablet daily, at the same time of day.

    Additional Dosage Information

    Missed doses
    If a tablet is forgotten, it should be taken as soon as the patient remembers, therapy should then continue as before. If 2 tablets or more have been missed, non-hormonal contraception must be used for the next 7 days of treatment.


    Cerebrovascular accident
    Focal migraine
    Hepatic neoplasm
    History of severe hepatic disorder
    History of venous thromboembolism
    Hormone dependent neoplasm
    Ischaemic heart disease
    Myocardial infarction
    Recent arterial thromboembolic disorder
    Severe hepatic disorder
    Thrombophilic disorder
    Undiagnosed gynaecological haemorrhage
    Venous thromboembolism

    Precautions and Warnings

    Predisposition to thromboembolic disease
    Prolonged immobilisation
    Recent surgery
    Recent trauma
    Severe headache
    Diabetes mellitus
    Glucose-galactose malabsorption syndrome
    Hepatic disorder
    History of depression
    Lactose intolerance

    Assess family medical history prior to commencing treatment
    Discontinue hormonal contraception before treatment initiation
    Contains lactose
    Exclude pregnancy prior to initiation of treatment
    Monitor blood pressure before starting treatment
    Perform a complete physical and gynaecological examination before therapy
    Abnormal and/or irregular bleeding should be investigated
    Monitor patients with a history of depression and/or suicide attempts
    Patients at risk of osteoporosis should have bone density assessed
    Advise patient to report any new or worsening depression/suicidal ideation
    Consider discontinuing treatment if serum transaminase levels rise
    Discontinue at the onset of severe depression
    May cause loss of bone mineral density
    May affect results of some laboratory tests
    Advise patient to seek advice at first indications of pregnancy
    Discontinue at first signs of jaundice
    Discontinue if arterial thromboembolism develops
    Discontinue if venous thromboembolism develops
    Suspend treatment if hypertension cannot be controlled
    Advise patient not to take St John's wort concurrently
    Female: Non-hormonal contraception required for 1 month after initiation
    Changes in menstrual bleeding patterns should be expected

    A dual X-ray absorptiometry (DXA) is recommended before commencing therapy in patients with risk factors for osteoporosis or bone loss.

    It is recommended that a DXA scan is completed after 1 year of treatment.

    Consider discontinuing treatment when the patient reaches menopause, as uterine fibroids are known to regress during menopause.

    Ovulation will return rapidly after discontinuing treatment in women of childbearing potential.

    Before discontinuing treatment, a discussion with the patient must take place regarding contraceptive methods to be started immediately after discontinuation of treatment.

    Periodic check-ups must be carried out during treatment.

    Women with suspected submucosal uterine fibroids must be made aware of the possibility of uterine fibroids prolapse or expulsion during treatment. Should the patient experience severe bleeding after bleeding symptoms have improved during treatment, they must contact their physician.

    Pregnancy and Lactation


    Relugolix with estradiol and norethisterone therapy is contraindicated during pregnancy.

    Should pregnancy occur, treatment should be discontinued immediately.

    Animal studies have shown teratogenic effects with exposure to relugolix in early pregnancy being associated with an increase in early miscarriage. Human data is limited and as such a potential risk cannot be ruled out.


    Relugolix with estradiol and norethisterone therapy is contraindicated during breastfeeding.

    Use of relugolix with estradiol and norethisterone when breastfeeding, and for 2 weeks following discontinuation of treatment, is contraindicated by the manufacturer.

    Animal data reports significant levels of relugolix in the breast milk however presence in human breast milk is unknown. Effects on exposed infants are unknown.

    Side Effects

    Breast cyst
    Hot flushes
    Menstrual disturbances
    Night sweats
    Reduced libido
    Uterine haemorrhage
    Uterine myoma

    Effects on Laboratory Tests

    Estrogens and progestogens may affect the results of laboratory tests such as parameters of the liver, thyroid, adrenal and renal function, plasma protein levels, parameters indicative of carbohydrate metabolism, coagulation and fibrinolysis.


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: November 2021

    Reference Sources

    Summary of Product Characteristics: Ryeqo tablets. Gedeon Richter (UK) Ltd. Revised August 2021.

    NICE Evidence Services Available at: Last accessed: 16 November 2021

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    Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content

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    FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.