RYEQO 40 mg/1 mg /0.5 Mg Film-Coated Tablets

Зміст інструкції

1. Ryeqo 40 mg/1 mg/0.5 mg film-coated tablets
   1. What is Ryeqo and what is it used for
   2. Cosa deve sapere prima di prendere Ryeqo
   3. How to take Ryeqo
   4. Possible side effects
   5. How to store Ryeqo
   6. Contents of the pack and other information

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

relugolix/estradiol/norethisterone acetate

Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicinal product. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before you start taking this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What is Ryeqo and what is it used for

Ryeqo contains the active ingredients relugolix, estradiol and norethisterone acetate.
It is used to treat

• moderate to severe symptoms of uterine fibroids (commonly known as myomas), which are non-cancerous tumors of the uterus.
• Symptoms associated with endometriosis in women with a clinical history of previous pharmacological or surgical treatments for their endometriosis (endometriosis is a often painful condition in which tissue similar to the tissue that normally lines the inside of the uterus - the endometrium - grows outside the uterus)

Ryeqo is used in adult women (over 18 years of age) before they reach menopause.
In some women, uterine fibroids can cause heavy menstrual bleeding (periods)
and pelvic pain (pain below the navel). Ryeqo is used to treat fibroids to stop or
reduce bleeding and reduce pain and discomfort in the pelvis associated with uterine fibroids.
Women with endometriosis may experience pelvic or lower abdominal pain, pain during
menstruation and pain during sexual intercourse. Ryeqo is used to treat endometriosis to
reduce symptoms due to the presence of tissue lining the uterus outside its natural location.
This medicine contains relugolix, which blocks certain receptors in the brain and this reduces the
production of hormones, which in turn stimulate the ovaries to produce estradiol and progesterone.
When these receptors are blocked, the levels of estrogen and progesterone circulating in the body
are reduced. 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 progestins. The inclusion of these hormones in Ryeqo maintains a hormonal state similar to the beginning of the menstrual cycle and therefore relieves symptoms but at the same time helps to
protect bone strength.

2. Cosa deve sapere prima di prendere Ryeqo

Non prenda Ryeqo
Do not take Ryeqo if you have any of the conditions listed below.
If you have any of the conditions listed below, tell your doctor:

• if you are allergicto relugolix, estradiol, norethisterone acetate or any of the other ingredients of this medicine (listed in section 6);
• if you have or have had a blood clot in a blood vesselin the legs (deep vein thrombosis), in the lungs (pulmonary embolism), in the heart (heart attack), in the brain (stroke) or in other parts of the body;
• if you have or have had a disease caused by blood clots in the arteries, such as heart attack, strokeor angina;
• if you have a blood clotting disorder(such as protein C deficiency, protein S deficiency, antithrombin-III deficiency or Factor V Leiden);
• if you suffer from osteoporosis;
• if you suffer from headachewith focal neurological symptoms such as paralysis or loss of muscle control, or migrainewith visual disturbances;
• if you have any type of tumorthat may worsen following exposure to female sex hormones, such as breast cancer or genital cancers;
• if you have or have ever had liver tumors;
• if you have or have ever had a liver diseaseand your liver function testshave not returned to normal;
• if you are pregnantor if you think you may be pregnantor if you are breastfeeding;
• if you have genital bleedingof unknown origin;
• if you are taking hormonal contraceptives(e.g. the contraceptive pill) and do not wish to stop using them.

If any of the above conditions occur for the first time while taking Ryeqo,
immediately stop treatment with Ryeqo and consult your doctor immediately.
If you are unsure whether any of the above conditions apply to you, ask your doctor before
taking Ryeqo.

Warnings and precautions
Talk to your doctor or pharmacist before taking Ryeqo.
You should know that most women experience reduced or absent menstruation during
treatment and for several weeks after it.
The doctor will discuss your medical and family history with you. The doctor will also check your
blood pressure and make sure you are not pregnant. You may also need a
physical examination and additional tests, such as a breast exam and a scan to measure how
strong your bones are, which will be specific to your needs and/or medical concerns.

Stop taking Ryeqo and urgently see a doctor if you notice:

• any of the conditions mentioned in the “Do not take Ryeqo” section;
• signs of liver disease:
• yellowing of the skin or whites of the eyes (jaundice);
• nausea or vomiting, fever, severe fatigue;
• dark urine, itching or upper abdominal pain;
• a significant increase in blood pressure(symptoms may include headache, fatigue, dizziness);
• migrainefor the first time or headachethat is unusually severe and occurs more often than before;
• possible signs of a blood clotthat may indicate you have a clot in your leg (deep vein thrombosis) or lung (pulmonary embolism), a heart attack or a stroke. For a description of the symptoms of these serious conditions, see the “Ryeqo and the risk of blood clots” section.
• If you become pregnant.

Tell your doctor if any of the following conditions apply to you:

• if you have one or more of the risk factors for developing a blood clotlisted below;
• if you have high blood pressure;
• if you suffer from osteoporosis;
• if you suffer from migraine;
• if you think you may be pregnant. Treatment with Ryeqo usually leads to a significant reduction in menstrual bleeding (“period”) or its cessation, making it difficult to recognize a pregnancy.
• if you suffer from or have previously suffered from depression;
• if you suffer from kidney impairment.

Ryeqo and the risk of blood clots
The use of other medicines containing an estrogen and a progestin increases the risk of blood
clots. The risk of blood clots associated with Ryeqo has not been established. Ryeqo reduces
estrogens 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 and/or artery:

• aging(especially after 35 years of age);
• overweight (body mass index >30 kg/m);
• if you have had major surgeryor prolonged immobility(e.g. leg in a cast);
• recent childbirth;
• close family member who has had a blood clot in the leg, lung or another organ, a heart attackor a strokeat a young age (e.g. before the age of 50);
• if you are a smoker;
• heart problems (valve disorders, a heart rhythm disorder called atrial fibrillation);
• diabetes;
• certain diseases such as systemic lupus erythematosus (SLE) - a disease affecting the body's natural defense system, sickle cell anemia (an inherited disease affecting red blood cells), Crohn's disease or ulcerative colitis (chronic inflammatory bowel diseases) or cancer.

The risk of developing a blood clot increases with the number of factors.
The symptoms of a blood clot depend on where the clot has formed.

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

• swelling of the leg and/or foot or along a vein in the leg;
• pain or tenderness in the leg that may only be felt when standing or walking;
• increased warmth in the affected leg with reddened or abnormally colored skin.

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

• sudden and unexplained shortness of breath and rapid breathing;
• sudden cough that may be associated with sharp chest pain;
• coughing up blood;
• severe dizziness or lightheadedness;
• rapid or irregular heartbeat.

Symptoms of aheart attack
Symptoms of a heart attack, also known as a myocardial infarction, can be
temporary and may include:

• pain, discomfort, pressure, heaviness, squeezing 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 dizziness;
• extreme weakness, anxiety or shortness of breath;
• rapid or irregular heartbeat.

Symptoms of astroke
Symptoms of a stroke may include:

• sudden numbness or weakness of the face, arm or leg, especially on one side of the body;
• sudden difficulty walking, dizziness, loss of balance or coordination;
• sudden confusion, difficulty speaking or understanding;
• sudden difficulty seeing with one or both eyes;
• sudden severe headache, prolonged or unusual, with no known cause;
• loss of consciousness or fainting with or without convulsions.

Surgery
If you are going to have surgery, tell your doctor 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 progestins, including Ryeqo. If you experience symptoms of jaundice, ask your doctor for advice.

Kidney impairment
If you experience a decrease in urine production or notice fluid retention causing
swelling in your legs, ankles or feet, ask your doctor for advice.

Changes in menstrual bleeding (“period”)
Treatment with Ryeqo usually leads to a significant reduction in menstrual bleeding
(“period”) or its cessation within the first 30 days of treatment. However, if you continue to
experience excessive bleeding, see your doctor.

Depression
If you experience changes in mood or depressive symptoms, ask your doctor for advice.

Hypertension
In rare cases, treatment with Ryeqo may lead to small increases in blood pressure. If
you experience symptoms of increased blood pressure, ask your doctor for advice.

Prolapse and expulsion of uterine fibroids
Uterine fibroids can develop anywhere within the muscular wall of the uterus,
including the submucosa, a thin layer of uterine tissue. In some women, the uterine fibroid may
protrude or slide through the cervix into the vagina and cause a significant worsening of
uterine bleeding or pain. If you experience heavy uterine bleeding again after an
improvement in symptoms during treatment with Ryeqo, ask your doctor for advice.

Gallbladder disorders
Some women who have taken estrogens and progestins, including Ryeqo, have reported gallbladder
disorders (gallstones or inflammation of the gallbladder). If you experience unusually severe pain
under the breastbone or in the upper abdomen, contact your doctor for advice.

Children and adolescents
Ryeqo should not be taken by girls under 18 years of age because the safety and efficacy
of Ryeqo have not been established in this age group.

Other medicines and Ryeqo
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
Consult 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 infection caused by the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)(e.g. ritonavir, efavirenz).
• Some medicines used to treat the 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 pulmonary hypertension(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(e.g. ranolazine, carvedilol, verapamil).
• Some medicines that prevent rejection of organs after transplantation(e.g. cyclosporine).
• St John's wort or hypericumpreparations (Hypericum perforatum).

Pregnancy and breastfeeding
Do not take Ryeqo if you are pregnant or breastfeeding. If you suspect you are pregnant or are
planning a pregnancy, ask your doctor for advice before taking this medicine. If you become
pregnant, stop taking Ryeqo and contact your doctor.
Ryeqo stops ovulation and therefore it is unlikely that you will become pregnant if you are taking it
as recommended. Ovulation and menstrual bleeding will return quickly after
stopping Ryeqo and you will need to start an alternative method of birth control (contraceptive)
immediately after stopping Ryeqo.
Depending on the time of your cycle when you start taking Ryeqo, it may take some time to
achieve complete inhibition of ovulation; therefore, you should use a non-hormonal contraceptive
method (e.g. condoms) for the first month after starting Ryeqo.
If you forget to take two or more tablets in a row, you should use a non-hormonal contraceptive
method (e.g. condoms) for the next 7 days of treatment.

Driving and using machines
Ryeqo has no known effects on the ability to drive and operate machines.

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

Ryeqo contains lactose
If your doctor has told you that you are intolerant to certain sugars, talk to your doctor before taking
this medicine.

3. How to take Ryeqo

Take this medicine exactly as your doctor has told you. If you have any doubts, ask your doctor or pharmacist.
The recommended dose is one tablet a day.
The tablet should be taken orally every day, at approximately the same time, with or without
food, with some liquid.
It is advisable to start taking Ryeqo within the first 5 days after the start of bleeding
due to your period. If you start taking it at another time during your menstrual cycle, you may initially experience
irregular or heavier bleeding.

If you take more Ryeqo than you should
No cases of serious harmful effects related to taking multiple doses of this medicine have been reported.
High doses of estrogens can cause nausea and vomiting and vaginal bleeding. If you have taken too many Ryeqo tablets, contact your doctor or pharmacist for advice.

If you forget to take Ryeqo
If you miss a tablet, take it as soon as you remember and then continue taking the
tablet the next day as usual. Do not take a double dose to make up for a missed
tablet.
If you forget to take two or more consecutive tablets, consult your doctor and use a non-
hormonal contraceptive (e.g. condoms) for the next 7 days of treatment.

If you stop taking Ryeqo
If you want to stop taking Ryeqo, talk to your doctor first. Your doctor will explain
the effects of stopping treatment and discuss other possibilities with you.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets 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 and are listed according to how
frequently they occur.
Very commonside effects (may affect more than 1 in 10 people):

• headache;
• hot flush.

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

• irritability;
• decreased sexual interest;
• dizziness;
• nausea;
• hair loss;
• increased sweating;
• night sweats;
• joint pain;
• excessive, irregular or prolonged uterine bleeding (uterine hemorrhage)
• vaginal dryness.

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

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

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. You can also report side effects directly
through the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-
avverse. By reporting side effects you can help provide more information on the
safety of this medicine.

5. How to store Ryeqo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the outer packaging and on the bottle
after Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Ryeqo contains

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

Description of the appearance of Ryeqo and contents of the pack
Ryeqo is a round, film-coated tablet, light yellow to yellow in colour, 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 a desiccant, closed with a child-resistant polypropylene cap with an induction seal or in
PVC/Al blisters with a desiccant packaged in a triplex PET/Al/PE sachet. Each pack
contains one or three bottles with 28 tablets; or two or six blisters with 14 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Gedeon Richter Plc.
Gyömrői út 19-21.
1103 Budapest
Hungary

Manufacturer (release batch sites)
Gedeon Richter Plc.
Gyömrői út 19-21.
1103 Budapest
Hungary

Other sources of information
More detailed information on this medicine is available on the European Medicines Agency website, http://www.ema.europa.eu .