Prospect: information for the user

Ryeqo 40 mg/1 mg/0.5 mg film-coated tablets

relugolix/estradiol/noretisterone acetate

This medicine is subject to additional monitoring, which will facilitate the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to take this medicine, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you must not give it to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or pharmacist, even if they do not appear in this prospect. See section 4.

Ryeqo contains the active principles relugolix, estradiol and noretisterone acetate.

It is used to treat

• mild to severe symptoms of uterine fibroids (also known as myomas), which are non-cancerous tumors of the uterus.
• symptoms associated with endometriosis in women with a history of previous medical or surgical treatment for endometriosis (endometriosis is a frequent and painful disorder in which tissue similar to the tissue that lines the inside of the uterus – the endometrium – grows outside the uterus).

Ryeqo is used in adult women (over 18 years old) who have not yet reached menopause.

In some women, uterine fibroids can cause heavy menstrual bleeding (also known as a period) and pelvic pain (pain below the navel). Ryeqo is used to treat uterine fibroids, to stop or reduce bleeding and alleviate pelvic pain and discomfort associated with uterine fibroids.

Women with endometriosis may experience pelvic pain or pain in the lower abdomen, menstrual pain and pain during sexual intercourse. Ryeqo is used to treat endometriosis to reduce symptoms caused by the displacement of the lining of the uterus.

This medication contains relugolix, which blocks certain receptors in the brain, reducing the production of hormones that stimulate the production of estradiol and progesterone in the ovaries. When blocked, circulating levels of estrogen and progesterone are reduced in the body. This medication also contains two types of female hormones, estradiol, which belongs to a group of medications called estrogens and noretisterone, which belongs to a group of medications called progestogens. The inclusion of these hormones in Ryeqo maintains a hormonal state similar to the beginning of the menstrual cycle, thus alleviating symptoms while protecting bone strength.

Do not take Ryeqo

Do not take Ryeqo if you have any of the conditions listed below.

If you have any of the conditions listed below, inform your doctor:

• If you areallergicto relugolix, estradiol, noretisterone or any of the other components of this medication (listed in section 6).
• If you have or have had previously ablood clot in a blood vesselin the legs (deep vein thrombosis), lungs (pulmonary embolism), heart (heart attack), brain (stroke) or in any other part of the body.
• If you have or have had previously a disease caused by blood clots in the arteries, such as aheart attack, a stroke or angina pectoris.
• If you have ablood clotting disorder(such as protein C deficiency, protein S deficiency, antithrombin III deficiency or factor V Leiden deficiency).
• If you haveosteoporosis.
• If you experienceheadacheswith neurological focal symptoms, such as paralysis or loss of muscle control, ormigraineswith visual disturbances.
• If you have any type ofcancerthat could worsen with exposure to female sex hormones, such asbreast cancer or genital organ cancer.
• If you have or have hadliver tumors.
• If you have or have had at any time aliver diseaseand theliver function test valueshave not returned to normal.
• If you arepregnantor think you may be pregnant or if you are inlactation.
• If you experience anyunexplained genital bleeding.
• If you are takinghormonal contraceptives(e.g., birth control pills) and do not want to stop using them.

If any of the above conditions appear for the first time while taking Ryeqo, stop taking it immediately and consult your doctor immediately.

If you are unsure about any of the above points, speak with your doctor before taking Ryeqo.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Ryeqo.

You should know that most women experience a reduced or absent menstrual period during treatment and for some weeks after.

Your doctor will ask about your medical history and family history. Your doctor will also need to monitor your blood pressure and ensure that you are not pregnant. You may also need to undergo a physical examination and other reviews, such as a breast examination or bone density test, specific to your needs and/or medical concerns.

Stop taking Ryeqo and seek medical attention urgently if you experience:

• Any of the situations indicated in the section «Do not take Ryeqo».
• If you notice signs of aliver disease:

• Yellowing of the skin or the white of the eyes (jaundice).
• Nausea or vomiting, fever, intense fatigue.
• Darkening of the urine, itching or pain in the upper abdominal region.
• A significant elevation of theblood pressure(the symptoms may be headache, fatigue, dizziness).
• Migrainefor the first time or unusually intense headaches that occur more frequently than before.
• If you notice what may be signs of ablood clotindicative of a clot in the leg (deep vein thrombosis) or in the lung (pulmonary embolism), a heart attack or a stroke. For a description of the symptoms of these serious diseases, see «Ryeqo and the risk of blood clots».
• If you becomepregnant.

Inform your doctor if you are in any of the following situations:

• If you have one or more of therisk factors for developinga blood clot that are listed below.
• If you havehigh blood pressure.
• If you haveosteoporosis.
• If you suffer frommigraines.
• If you think you may bepregnant.Most women experience a significant reduction in menstrual bleeding (period) or its complete absence during Ryeqo treatment, making it difficult to recognize a pregnancy.
• If you have or have haddepression.
• If you have akidney disease (renal disease).

Ryeqo and the risk of blood clots

The use of other medications containing estrogen and progestogen increases the risk of blood clots. The risk of blood clots with Ryeqo has not been determined. Ryeqo reduces estrogen to levels similar to those at the beginning of a normal menstrual cycle.

Factors that may increase the risk of blood clots in a vein or artery:

• As youage(especially over 35 years).
• If you areoverweight(BMI> 30 kg/m2).
• If you have undergone amajor surgeryorhave been immobile for a prolonged period(e.g., if you have had a leg cast).
• If you havegiven birth recently.
• If a close relative has had ablood clot in the leg, lung or other organ, aheart attackor astroke at a young age(e.g., under 50 years).
• If yousmoke.
• If you have aheart problem (valve disorder, or heart rhythm alteration, known asatrial fibrillation).
• If you havediabetes.
• If you have diseases such assystemic lupus erythematosus(SLE - a disease that affects your natural defense system),sickle cell anemia(a hereditary disease of red blood cells),Crohn's diseaseorulcerative colitis(chronic inflammatory bowel diseases), orcancer.

The more factors you have, the greater your risk of developing a blood clot.

The symptoms of a blood clot depend on where it has occurred.

Symptoms of a blood clot in the leg (deep vein thrombosis; DVT)

The symptoms of a blood clot in the leg, known as deep vein thrombosis (DVT), may include:

• Swelling in the leg and/or foot along a vein in the leg.
• Pain or sensitivity in the leg, which worsens when standing or walking.
• Increased temperature in the affected leg accompanied by redness or discoloration of the skin.

Symptoms of a blood clot in the lung (pulmonary embolism; PE)

The symptoms of a blood clot in the lung, known as pulmonary embolism (PE), may include:

• Sudden shortness of breath without known cause or rapid breathing of sudden onset and inexplicable.
• Sudden cough that may be accompanied by sharp chest pain.
• Coughing up blood.
• Intense dizziness or fainting.
• Irregular or rapid heartbeats.

Symptoms of aheart attack

The symptoms of a heart attack, also known as myocardial infarction, may be temporary and include:

• Pain, discomfort, pressure, fullness, or a sensation of oppression or plenitude in the chest, arm, or below the sternum.
• Discomfort that radiates to the back, jaw, throat, arm, or stomach.
• Sensation of fullness, indigestion, or choking.
• Sweating, nausea, vomiting, or dizziness.
• Extreme weakness, anxiety, or shortness of breath.
• Irregular or rapid heartbeats.

Symptoms of astroke

The symptoms of a stroke may include:

• Instant numbness or weakness in the face, arm, or leg, especially on one side of the body.
• Sudden difficulty walking, dizziness, loss of balance, or loss of coordination.
• Sudden confusion, difficulty speaking, or understanding.
• Sudden vision loss in one eye or both eyes.
• Sudden severe headache, dizziness, or fainting.
• Loss of consciousness or fainting with or without convulsions.

Surgery

If you are to undergo surgery, inform the surgeon that you are taking Ryeqo.

Liver tumors or liver disease

In rare cases, liver tumors or liver disease have been reported in women taking estrogen and progestogen-containing medications, including Ryeqo. If you experience any symptoms of jaundice, contact your doctor for advice.

Kidney disease (renal disease)

If you notice a decrease in urine output or any fluid retention that causes swelling in the legs, ankles, or feet, contact your doctor for advice.

Change in menstrual bleeding pattern (period)

Most women experience a significant reduction in menstrual bleeding (period) or its complete absence during the first 30 days of treatment with Ryeqo. However, if you continue to experience excessive bleeding, inform your doctor.

Depression

If you experience any mood changes or symptoms of depression, contact your doctor for advice.

Increased blood pressure

In rare cases, treatment with Ryeqo may cause mild increases in blood pressure. If you experience any symptoms of increased blood pressure, contact your doctor for advice.

Uterine fibroid prolapse and expulsion

Uterine fibroids may develop anywhere within the muscular wall of the uterus, including the submucosa, a thin layer of tissue in the uterus. In some women, the fibroid may protrude or pass through the uterine cervix into the vagina and cause a significant worsening of uterine bleeding or pain. If you experience a return of heavy bleeding after your symptoms have improved with Ryeqo treatment, contact your doctor for advice.

Biliary tract disorders

Some women taking estrogen and progestogen-containing medications, including Ryeqo, have reported biliary tract disorders (gallstones or inflammation of the gallbladder). If you experience severe, unexplained pain in the upper abdomen or below the chest, contact your doctor for advice.

Children and adolescents

Girls under 18 years old should not take Ryeqo, as the safety and efficacy of Ryeqo in this age group have not been determined.

Other medications and Ryeqo

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Speak with your doctor if you are taking any of the medications listed below, as they may affect Ryeqo or be affected by Ryeqo:

• Some medications used to treatepilepsy(e.g., carbamazepine, topiramate, phenytoin, phenobarbital, primidone, oxcarbazepine, felbamate).
• Some medications used to treatHIV/AIDS(e.g., ritonavir, efavirenz).
• Some medications used to treathepatitis C virus (HCV)(e.g., boceprevir, sofosbuvir, velpatasvir, voxilaprevir, telaprevir, glecaprevir).
• Some medications used to treatfungal infections(e.g., ketoconazole, itraconazole, fluconazole, griseofulvin).
• Some medications used to treatbacterial infections(e.g., rifampicin, rifabutin, clarithromycin, erythromycin, gentamicin, tetracycline, griseofulvin).
• Some medications used to treathigh blood pressure in the pulmonary arteries(e.g., bosentan).
• Some medications used to treathigh blood pressure(e.g., diltiazem, carvedilol, verapamil).
• Some medications used to treatirregular heartbeats(e.g., amiodarone, dronedarone, propafenone, quinidine, verapamil).
• Some medications used to treatangina pectoris(e.g., ranolazine, carvedilol, verapamil).
• Some medications used to prevent organ rejection after transplantation(e.g., cyclosporin).
• Herbal medications containingSt. John's Wort(Hypericum perforatum).

Pregnancy and lactation

Do not take Ryeqo if you are pregnant or breastfeeding. If you think you may be pregnant or plan to become pregnant, consult your doctor before using this medication. If you become pregnant, stop taking Ryeqo and contact your doctor.

Ryeqo inhibits ovulation and it is unlikely that you will become pregnant while taking Ryeqo as directed. Ovulation and menstrual bleeding will return quickly after stopping Ryeqo treatment, and you will need to start an alternative contraceptive method immediately after stopping Ryeqo treatment.

Depending on when you started taking Ryeqo in your cycle, it may take some time for Ryeqo to completely inhibit ovulation; therefore, non-hormonal contraceptive methods (e.g., condoms) should be used during the first month of Ryeqo treatment.

If you miss two or more consecutive tablets, use a non-hormonal contraceptive method (e.g., condoms) for the next 7 days of treatment.

Driving and operating machinery

Ryeqo has no known effect on the ability to drive and operate machinery.

Blood tests

If you need to have a blood test or urine test, inform your doctor or laboratory staff that you are taking Ryeqo, as this medication may affect the results of some blood tests.

Ryeqo contains lactose

If your doctor has told you that you have a lactose intolerance, consult with them before taking this medication.

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

The recommended dose is one tablet per day.

The tablet should be taken orally every day, approximately at the same time, with or without food and with a little liquid.

It is recommended to start taking Ryeqo in the first 5 days after the onset of menstrual bleeding. If you start treatment at another time in your menstrual cycle, you may experience irregular or more abundant bleeding.

If you take more Ryeqo than you should

There are no reports of severe adverse effects caused by taking multiple doses of this medication at the same time. High doses of estrogen may cause nausea and vomiting, and vaginal bleeding. If you have taken too many Ryeqo tablets, consult your doctor or pharmacist.

If you forget to take Ryeqo

If you forget a tablet, take it as soon as you remember and resume taking the tablet the next day as usual. Do not take a double dose to compensate for the missed doses.

If you forget to take two or more tablets consecutively, consult your doctor and use a non-hormonal contraceptive method (e.g., condom) for the next 7 days of treatment.

If you interrupt treatment with Ryeqo

If you wish to discontinue treatment with Ryeqo, speak first with your doctor. Your doctor will explain the effects of discontinuing treatment and discuss other options with you.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medications, this medication may produce adverse effects, although not all people may experience them.

Seek urgent medical assistance if you experience any of the following signs and symptoms of an allergic reaction:

• Swelling of the lips, face, or throat.

The following adverse effects have been reported with Ryeqo, based on their frequency of occurrence.

Adverse EffectsVery Frequent(may affect more than 1 in 10 people):

• Headache,
• Hot flashes.

Adverse EffectsFrequent(may affect up to 1 in 10 people):

• Irritability,
• Decreased interest in sex,
• Dizziness,
• Nausea,
• Hair loss,
• Increased sweating,
• Nocturnal sweating,
• Joint pain,
• Excessive, irregular, or prolonged uterine bleeding,
• Vaginal dryness.

Adverse EffectsRare(may affect up to 1 in 100 people):

• Indigestion,
• Hives (urticaria),
• Angioedema (rapid inflammation of the mucous membranes or skin that may occur on the face, mouth, tongue, abdomen, or arms and legs),
• Mammary gland cyst,
• Uterine fibroid expulsion (the fibroid partially or completely exits through the vagina, often with increased vaginal bleeding).

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the outer box and the bottle after CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Ryeqo

• The active principles are relugolix, estradiol, and noretisterone acetate. A film-coated tablet contains 40 mg of relugolix, 1 mg of estradiol, and 0.5 mg of noretisterone acetate.
• The remaining components are lactose monohydrate, mannitol (E421), sodium glycolate starch, hydroxypropylcellulose (E463), magnesium stearate (E572), hypromellose type 2910 (E464), titanium dioxide (E171), triacetin (E1518), and yellow iron oxide (E172).

Appearance of Ryeqo and contents of the packaging

Ryeqo is a round, film-coated tablet, yellowish in color, 8 mm in diameter, with "415" on one side and smooth on the other side. It is available in high-density polyethylene (HDPE) bottles with desiccant, closed with induction-sealed polypropylene caps and child-resistant closures, or PVC/Al blisters with desiccant packaged in a PET/Al/PE triple-layer laminate. Each box contains one or three bottles with 28 tablets; or two or six blisters with 14 tablets.

It may be the case that only some sizes of packaging are commercially available.

Marketing Authorization Holder

Gedeon Richter Plc.

Gyömroi út 19-21.

1103 Budapest

Hungary

Responsible for Manufacturing (Batch Release Sites)

Gedeon Richter Plc.

Gyömroi út 19-21.

1103 Budapest

Hungary

Last review date of this leaflet:23 February 2024

Other sources of information

Detailed information about this medicine is available on the European Medicines Agency website:http://www.ema.europa.eu.