RYEQO 40 MG/1 MG/0.5 MG FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

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

relugolix/estradiol/norethisterone acetate

This medicine is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. The last section of section 4 will tell you how to report side effects.

Read all of this leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Ryeqo and what is it used for
2. What you need to know before you take Ryeqo
3. How to take Ryeqo
4. Possible side effects
5. Storage of Ryeqo
6. Contents of the pack and other information

1. What is Ryeqo and what is it used for

Ryeqo contains the active substances relugolix, estradiol, and norethisterone acetate.

It is used to treat

• moderate 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 common 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 of age) who have not reached menopause.

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

Women with endometriosis may experience pelvic pain or lower abdominal pain, pain during menstrual periods, and during sexual intercourse. Ryeqo is used to treat endometriosis in order to reduce symptoms due to displacement of uterine lining tissue.

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

2. What you need to know before you take Ryeqo

Do not take Ryeqo

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

If you have any of the diseases listed below, you should tell your doctor:

• If you are allergicto relugolix, estradiol, norethisterone, or any of the other components of this medicine (listed in section 6).
• If you have had a blood clot in a blood vesselin your legs (deep vein thrombosis), lungs (pulmonary embolism), heart (heart attack), brain (stroke), or in any other part of your body.
• If you have or have had a disease caused by blood clots in the arteries, such as a heart attack, stroke, or angina pectoris.
• If you have a blood clotting disorder(such as protein C, protein S, antithrombin III, or factor V Leiden deficiency).
• If you have osteoporosis.
• If you experience headacheswith focal neurological symptoms, such as paralysis or loss of muscle control, or migraineswith visual disturbances.
• If you have any type of cancerthat could worsen with exposure to female sex hormones, such as breast cancer or cancer of the genital organs.
• If you have or have had liver tumors.
• If you have or have had liver diseaseand your liver function test values have not returned to normal.
• If you are pregnantor think you may be pregnantor if you are breastfeeding.
• If you experience any genital bleedingof unknown origin.
• If you are taking hormonal contraceptives(e.g., birth control pills) and do not want to stop using them.

If any of the above diseases occur for the first time while you are taking Ryeqo, stop taking it immediately and consult your doctor.

If you are unsure about any of the above points, talk to 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 reduced or no menstrual bleeding (period) during treatment and for some weeks after.

Your doctor will ask you about your medical and family history. Your doctor will also need to check your blood pressure and make sure you are not pregnant. You may also need to have a physical examination and other checks, such as a breast examination or bone density test, specific to your medical needs and/or concerns.

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

• Any of the situations listed in the section "Do not take Ryeqo".
• If you notice signs of liver disease:

• Yellowing of the skin or the whites of the eyes (jaundice).
• Nausea or vomiting, fever, extreme fatigue.
• Darkening of the urine, itching, or pain in the upper abdominal region.
• A significant increase in blood pressure(symptoms may be headache, fatigue, dizziness).
• Migrainefor the first time or unusually severe headachesthat occur more frequently than before.
• If you notice what may be signs of a blood clotindicating a clot in the leg (i.e., deep vein thrombosis) or in the lung (i.e., pulmonary embolism), a heart attack, or a stroke. To see a description of the symptoms of these serious diseases, see "Ryeqo and the risk of blood clots".
• If you become pregnant.

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

• If you have one or more risk factors for developinga blood clot that are listed below.
• If you have high blood pressure.
• If you have osteoporosis.
• If you suffer from migraines.
• If you think you may be pregnant.Usually, treatment with Ryeqo results in a significant reduction in menstrual bleeding (period) or its complete disappearance, which makes it difficult to recognize a pregnancy.
• If you have had depressionbefore.
• If you have kidney disease.

Ryeqo and the risk of blood clots

The use of other medicines that contain an estrogen and a 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 a blood clot in a vein or artery:

• As you get older(especially from 35 years onwards).
• If you are overweight(body mass index > 30 kg/m2).
• If you have had major surgeryor have been immobilized for a long time(e.g., if you have had a leg in a cast).
• If you have recently given birth.
• If a close relative has had a blood clot in the leg, lung, or other organ, a heart attack, or a stroke at a young age(e.g., under 50 years).
• If you smoke.
• If you have a heart problem(valve disorder or heart rhythm disturbance, called atrial fibrillation).
• If you have diabetes.
• If you have diseases such as systemic lupus erythematosus(SLE - a disease that affects your natural defense system), sickle cell anemia(a hereditary disease of red blood cells), Crohn's diseaseor ulcerative colitis(chronic inflammatory bowel diseases), or cancer.

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), can include:

• Swelling of the leg and/or foot along a vein in the leg.
• Pain or tenderness 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), can include:

• Sudden shortness of breath without known cause or sudden rapid breathing.
• Sudden cough that may be accompanied by sharp chest pain.
• Coughing up blood.
• Severe dizziness or fainting.
• Rapid or irregular heartbeat.

Symptoms of aheart attack

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

• Pain, discomfort, pressure, heaviness, sensation of tightness, or fullness in the chest, arm, or below the breastbone.
• Discomfort that radiates to the back, jaw, throat, arm, or stomach.
• Feeling of fullness, indigestion, or choking.
• Sweating, nausea, vomiting, or fainting.
• Extreme weakness, anxiety, or shortness of breath.
• Rapid or irregular heartbeat.

Symptoms of astroke

The symptoms of a stroke can include:

• Sudden 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 difficulty seeing in one eye or both.
• Sudden severe headache with no known cause.
• Loss of consciousness or fainting with or without seizures.

Surgery

If you are going to have surgery, tell 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 estrogens and progestogens. If you experience any symptoms of jaundice, contact your doctor for advice.

Kidney failure

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

Change in menstrual bleeding pattern (period)

Usually, treatment with Ryeqo results in a significant reduction in menstrual bleeding (the "period") or its complete disappearance within the first 30 days of treatment. However, if you continue to experience excessive bleeding, tell your doctor.

Depression

If you have mood changes or any depressive symptoms, 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 can develop in any part of 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 cervix into the vagina, causing significant worsening of uterine bleeding or pain. If you experience heavy bleeding again after your symptoms have improved with Ryeqo treatment, contact your doctor for advice.

Gallbladder disorders

Some women taking medicines that contain estrogen and progestogen, including Ryeqo, have reported gallbladder disorders (gallstones or gallbladder inflammation). If you experience unusually severe pain under the ribcage or in the upper abdomen, contact your doctor for advice.

Children and adolescents

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

Other medicines and Ryeqo

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Talk to your doctor if you are taking any of the medicines listed below, as they may affect Ryeqo or be affected by Ryeqo:

• Some medicines used to treat epilepsy(e.g., carbamazepine, topiramate, phenytoin, phenobarbital, primidone, oxcarbazepine, felbamate).
• Some medicines used to treat HIV/AIDS(e.g., ritonavir, efavirenz).
• Some medicines used to treat hepatitis C virus (HCV)(e.g., boceprevir, sofosbuvir, velpatasvir, voxilaprevir, telaprevir, glecaprevir).
• Some medicines used to treat fungal infections(e.g., ketoconazole, itraconazole, fluconazole, griseofulvin).
• Some medicines used to treat bacterial infections(e.g., rifampicin, rifabutin, clarithromycin, erythromycin, gentamicin, tetracycline, griseofulvin).
• Some medicines used to treat high blood pressure in the pulmonary arteries(e.g., bosentan).
• Some medicines used to treat high blood pressure(e.g., diltiazem, carvedilol, verapamil).
• Some medicines used to treat irregular heartbeats(e.g., amiodarone, dronedarone, propafenone, quinidine, verapamil).
• Some medicines used to treat angina pectoris(e.g., ranolazine, carvedilol, verapamil).
• Some medicines used to prevent organ rejection after transplantation(e.g., cyclosporine).
• Herbal medicines containing St. John's Wort(Hypericum perforatum).

Pregnancy and breastfeeding

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 medicine. If you become pregnant, stop taking Ryeqo and contact your doctor.

Ryeqo interrupts ovulation and, therefore, it is unlikely that you will become pregnant if you are using Ryeqo as recommended. Ovulation and menstrual bleeding will return quickly after stopping treatment with Ryeqo, and alternative contraceptive control should be initiated immediately after stopping treatment with Ryeqo.

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

If you miss two or more tablets in a row, a non-hormonal contraceptive method (e.g., condoms) should be used for the next 7 days of treatment.

Driving and using machines

Ryeqo has no known effect on the ability to drive and use machines.

Lab tests

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

Ryeqo contains lactose

If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Ryeqo

Follow exactly the administration instructions of this medication indicated by your doctor. In case of 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 that you start taking Ryeqo in the first 5 days after the start of menstrual bleeding. If you start treatment at another time in your menstrual cycle, you may experience irregular or heavier bleeding.

If you take more Ryeqo than you should

There are no reports of serious harmful effects caused by taking several doses of this medication at once. 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 take the next tablet at the usual time. Do not take a double dose to make up for forgotten doses.

If you forget to take two or more tablets in a row, 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 interrupt treatment with Ryeqo, talk to your doctor first. Your doctor will explain the effects of interrupting treatment and discuss other possibilities with you.

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

4. Possible adverse effects

Like all medications, this medication can cause adverse effects, although not all people experience them.

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

• swelling of the lips, face, or throat.

The following side effects have been reported with Ryeqo, classified by frequency:

Very commonadverse effects (may affect more than 1 in 10 people):

• headache,
• hot flashes.

Commonadverse effects (may affect up to 1 in 10 people):

• irritability,
• decreased interest in sex,
• dizziness,
• nausea,
• hair loss,
• increased sweating,
• night sweats,
• joint pain,
• excessive, irregular, or prolonged uterine bleeding (uterine bleeding),
• dryness of the genital area.

Uncommonadverse effects (may affect up to 1 in 100 people):

• indigestion,
• hives (urticaria),
• angioedema (rapid swelling of the mucous membranes or skin that can occur in the face, mouth, tongue, abdomen, or arms and legs),
• breast lump (breast cyst),
• expulsion of the uterine fibroid (the fibroid comes out totally or partially through the vagina, usually with increased vaginal bleeding).

Reporting of 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 leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Ryeqo

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

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

This medication does not require special storage conditions.

Medications should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Ryeqo

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

Appearance of Ryeqo and package contents

Ryeqo is a round, film-coated tablet, light yellow to yellow in color, 8 mm in size, with "415" on one side and smooth on the other side. It is available in high-density polyethylene (HDPE) bottles with a desiccant, closed with a polypropylene cap sealed by induction and child-resistant closure, or in PVC/Al blisters with a desiccant packaged in a triplex laminate PET/Al/PE pouch. Each carton contains one or three bottles with 28 tablets, or two or six blisters with 14 tablets.

Only some pack sizes may be marketed.

Marketing authorization holder

Gedeon Richter Plc.

Gyömroi út 19-21.

1103 Budapest

Hungary

Manufacturer (batch release sites)

Gedeon Richter Plc.

Gyömroi út 19-21.

1103 Budapest

Hungary

Date of last revision of this leaflet:23 February 2024

Other sources of information

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