InfoCons Consumer Protection informs you – FYLREVY – Package Leaflet

Before anything else

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.

ℹ️ 1. What FYLREVY is and what it is used for

FYLREVY is a hormone r eplacement therapy (HRT). It contains the natural oestrogen hormone , estetrol. FYLREVY is used in :

• postmenopausal women who have had their uterus (womb) removed (have had a hysterectomy ), and;
• postmenopausal women with an intact uterus (have not had a hysterectomy) and who have not had a natural menstrual period for at least 12 months .

Relief of symptoms occurring after menopause During the menopause, the amount of the oestrogen produced by a woman’s body drops. This can cause symptoms such as hot face, neck and chest (“hot flushes”). FYLREVY alleviates these symptoms after menopause. You will only be prescribed FYLREVY if your symptoms seriously hinder your daily life.

⚠️ 2. What you need to know before you take FYLREVY

Medical history and regular check -ups The use of HRT carries risks which need to be considered when deciding whether to start taking it, or whether to carry on taking it.

The experience in treating women with a premature menopause (due to ovarian failure or surgery) is limited. If you have a premature menopause the risks of using HRT may be different. Please talk to your doctor.

34 Before you start (or restart) HRT, your doctor will ask about your own and your family’s medical history. Your doctor may decide to perform a physical examination. This may include an examination of your breasts and/or an internal examination, if necessary.

Once you have started on FYLREVY you should see your doctor for regular check- ups (at least once a year). At these check -ups, discuss with your doctor the benefits and risks of continuing with FYLREVY .

Go for regular breast screening, as recommended by your doctor .

Do not take FYLREVY

If any of the following applies to you. If you are not sure about any of the points below, talk to your doctor before taking FYLREVY .

Do not take FYLREVY

• If you are allergic (hypersensitive) to estetrol , or any of the other ingredients of this medicine (listed in section 6);
• If you have or have ever had breast cancer, or if you are suspected of having it;
• If you have cancer which is sensitive to oestrogens, such as cancer of the womb lining (endometrium), or if you are suspected of having it;
• If you have any unexplained vaginal bleeding ;
• If you have excessive thickening of the womb lining that is not being treated;
• If you have or have ever had a blood clot in a vein (thrombosis), such as in the legs (deep venous thrombosis) or the lungs (pulmonary embolism);
• If you have a blood clotting disorder (such as protein C, protein S, or antithrombin deficiency);
• If you have or recently have had a disease caused by blood clots in the arteries, such as a heart attack, stroke or angina;
• If you have or have ever had a liver disease and your liver function tests have not returned to normal;
• If you have a rare blood problem called “porphyria” which is passed down in families (inherited) .

If any of the above conditions appear for the first time while taki ng FYLREVY , stop taking it at once and consult you r doctor immediately .

Warnings and precautions

Talk to your doctor or pharmacist before taking FYLREVY .

Tell your doctor if you have ever had any of the following problems, before you start the treatment, as these may return or become worse during treatment with FYLREVY . If so, you should see your doctor more often for check- ups:

• fibroids inside your womb;
• growth of womb lining outside your womb (endometriosis) or a history of excessive growth of the womb lining (endometrial hyperplasia);
• increased risk of developing blood clots (see “Blood clots in a vein (thrombosis)”);
• increased risk of getting an oestrogen- sensitive cancer (such as having a mother, sister or grandmother who has had breast cancer);
• high blood pressure;
• a liver disorder, such as a benign liver tumour;
• diabetes;
• gallstones;
• migraine or severe headaches;
• a disease of the immune system that affects many organs of the body (systemic lupus erythematosus, SLE);
• epilepsy;
• asthma;

35 – a disease affecting the eardrum and hearing (otosclerosis);

• a very high level of fat in your blood (triglycerides);
• fluid retention due to cardiac or kidney problems;
• hereditary and acquired angioedema.

Stop taking FYLREVY and see a doctor immediately If you notice any of the following when taking HRT:

• any of the conditions mentioned in the ‘DO NOT take FYLREVY ’ section;
• yellowing of your skin or the whites of your eyes (jaundice). These may be signs of a liver disease;
• swollen face, tongue and/or throat and/or difficulty swallowing or hives, together with difficulty breathing which are suggestive of an angioedema;
• a large rise in your blood pressure (symptoms may be headache, tiredness, dizziness) ;
• migraine -like headaches which happen for the first time;
• if you become pregnant;
• if you notice signs of a blood clot, such as:
• painful swelling and redness of the legs;
• sudden chest pain;
• difficulty in breathing;

For more information, see ‘Blood clots in a vein (thrombosis)’ Note: FYLREVY is not a contraceptive. If it is less than 12 months since your last menstrual period or you are under 50 years old, you may still need to use additional contraception to prevent pregnancy.

Speak to your doctor for advice.

HRT and cancer Excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the lining of the womb (endometrial cancer) Taking oestrogen- only HRT will increase the risk of excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the womb lining (endometrial cancer).

Taking a progestogen in addition to the oestrogen for at least 12 days of each 28- day cycle protects you from this extra risk. So, your doctor will prescribe a progestogen separately if you still have your womb. If you have had your womb removed (a hystere ctomy), discuss with your doctor whether you can safely take this product without a progestogen.

In women who still have a womb and who are not taking HRT, on average, 5 in 1 000 will be diagnosed with endometrial cancer between the ages of 50 and 65.

For women aged 50 to 65 who still have a womb and who take oestrogen- only HRT, between 10 and 60 women in 1 000 will be diagnosed with endometrial cancer (i.e. between 5 and 55 extra cases), depending on the dose and for how long it is taken.

FYLREVY contains a higher dose of oestrogens than other oestrogen- only HRT products. The risk of endometrium cancer when using together with a progestogen is not known.

Breast cancer Evidence shows that taking combined oestrogen- progestogen and or oestrogen- only HRT increases the risk of breast cancer. The extra risk depends on how long you use HRT. The additional risk becomes clear within 3 years of use. After stopping HRT, the extra risk will decrease with time, but the risk may persist for 10 years or more if you have used HRT for more than 5 years.

Compare Women aged 50 to 54 who are not taking HRT, on average, 13 to 17 in 1 000 will be diagnosed with breast cancer over a 5 -year period.

For women aged 50 who start taking oestrogen- only HRT for 5 years, there will be 16- 17 cases in 1 000 users (i.e. an extra 0 to 3 cases).

For women aged 50 who start taking oestrogen- progestogen HRT for 5 years, there will be 21 cases in 1 000 users (i.e. an extra 4 to 8 cases).

Women aged 50 to 59 who are not taking HRT, on average, 27 in 1 000 will be diagnosed with breast cancer over a 10 -year period.

For women aged 50 who start taking oestrogen- only HRT for 10 years, there will be 34 cases in 1 000 users (i.e. an extra 7 cases).

For women aged 50 who start taking oestrogen- progestogen HRT for 10 years, there will be 48 cases in 1 000 users (i.e. 21 extra cases).

Regularly check your breasts. See your doctor if you notice any changes such as:

• dimpling of the skin;
• changes in the nipple;
• any lumps you can see or feel;

Additionally, you are advised to join mammography screening programs when offered to you. For mammogram screening, it is important that you inform the nurse/healthcare professional who is actually taking the x- ray that you use HRT, as this medication may i ncrease the density of your breasts which may affect the outcome of the mammogram. Where the density of the breast is increased, mammography may not detect all lumps.

Ovarian cancer Ovarian cancer is rare – much rarer than breast cancer. The use of oestrogen -only or combined oestrogen- progest ogen HRT has been associated with a slightly increased risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women aged 50 to 54 who are not taking HRT, about 2 women in 2 000 will be diagnosed with ovarian cancer over a 5- year period. For women who have been taking HRT for 5 years, there will be about 3 cases per 2 000 users (i.e. about 1 extra case).

Effect of HRT on heart and circulation Blood clots in a vein (thrombosis) The risk of blood clots in the veins is about 1.3 to 3 times higher in HRT users than in non- users, especially during the first year of taking it.

Blood clots can be serious, and if one travels to the lungs, it can cause chest pain, breathlessness, fainting or even death.

You are more likely to get a blood clot in your veins as you get older and if any of the following applies to you. Inform your doctor if any of these situations applies to you:

• you are unable to walk for a long time because of major surgery, injury or illness (see also section 3, If you need to have surgery);
• you are seriously overweight (BMI > 30 kg/m 2);
• you have any blood clotting problem that needs long- term treatment with a medicine used to prevent blood clots;
• if any of your close relatives has ever had a blood clot in the leg, lung or another organ;
• you have systemic lupus erythematosus (SLE);
• you have cancer;

For signs of a blood clot, see “Stop taking FYLREVY and see a doctor immediately”.

Compare Looking at women in their 50s who are not taking HRT, on average, over a 5- year period, 4 to 7 in 1 000 would be expected to get a blood clot in a vein.

For women in their 50s who have been taking oestrogen- progestogen HRT for over 5 years, there will be 9 to 12 cases in 1 000 users (i.e.an extra 5 cases).

For women in their 50s who have had their womb removed and have been taking oestrogen- only HRT for over 5 years, there will be 5 to 8 cases in 1 000 users (i.e. 1 extra case).

Heart disease (heart attack) There is no evidence that HRT will prevent a heart attack.

Women over the age of 60 years who use oestrogen- progestogen HRT are slightly more likely to develop heart disease than those not taking any HRT.

For women who have had their womb removed and are taking oestrogen- only therapy there is no increased risk of developing heart disease.

Stroke The risk of getting a stroke is about 1.5 times higher in HRT users than in non-users. The number of extra cases of stroke due to use of HRT will increase with age.

Compare Looking at women in their 50s who are not taking HRT, on average, 8 in 1 000 would be expected to have a stroke over a 5- year period. For women in their 50s who are taking HRT, there will be 11 cases in 1 000 users, over 5 years (i.e. an extra 3 cases).

Other conditions

• HRT will not prevent memory loss. There is some evidence of a higher risk of memory loss in women who start using HRT after the age of 65. Speak to your doctor for advice .

Children and adolescents

FYLREVY should not be taken by children and adolescents.

Other medicines and FYLREVY

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines including medicines obtained without a prescription, herbal medicines or other natural products.

Some medicines may interfere with the effect of some HRTs. FYLREVY has a low potential for interacting with other drugs.

HRT can affect the way some other medicines work:

• Medicines for Hepatitis C virus (HCV) (such as combination regimen s ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin; glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir may cause increases in liver function blood test results (increase in alanine aminotransferase ( ALT ) liver enzyme) in women

using CHCs containing ethinylestradiol. FYLREVY contains estetrol instead of ethinylestradiol.

It is not known whether an increase in ALT liver enzyme can occur when using FYLREVY with this HCV combination regimen.

Laboratory tests If you need a blood test, tell your doctor or the laboratory staff that you are taking FYLREVY , because this medicine can affect the results of some tests.

38 FYLREVY with food and drink FYLREVY may be taken with or without food, if necessary, with a small amount of water.

Pregnancy and breast -feeding FYLREVY is for use in postmenopausal women only. If you become pregnant, stop taking FYLREVY and contact your doctor .

Driving and using machines

FYLREVY has no or negligible influence on the ability to drive and use machines.

FYLREVY contains lactose and sodium

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine .

This medicine contains less than 1 mmol sodium (23 mg) per film -coated tablet, that is to say essentially ‘sodium -free’.

💊 3. How to take FYLREVY

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Your doctor will aim to prescribe the lowest dose to treat your symptom for as short as necessary.

In women without a uterus (womb), FYLREVY 18.9 mg should be used.

Speak to your doctor if you think this dose is too strong or not strong enough.

Take one tablet each day at about the same time, with some water if necessary.

Continuous administration is recommended.

Women with an intact uterus may experience irregular vaginal bleeding or spotting (minimal blood loss requiring at most one tampon) while taking FYLREVY , mainly during the first 3 months of treatment. In case of persistent or significant vaginal bleeding, talk to your doctor.

If you still have a uterus, FYLREVY must be taken in combination with a progestogen continuously as prescribed by your doctor .

If you take more FYLREVY than you should

There are no reports of serious harm ful results of taking too many FYLREVY tablets.

If you take several FYLREVY tablets at once, you may feel sick, experience low abdominal pain, nipple pain, or vomit or bleed from the vagina.

If you have taken too many FYLREVY tablets, or you discover that a child has taken some, ask your doctor or pharmacist for advice.

If you forget to take FYLREVY

If you forgot to take a tablet at your usual time , it should be taken as soon as possible. If more than 12 hours have pass ed, do not take the forgotten tablet and take the next tablet at the usual time. Do not take an extra table to make up for a forgotten dose.

Missed tablets may increase the likelihood of breakthrough bleeding or spotting in women with a uterus.

If you stop taking FYLREVY

You can stop taking FYLREVY at any time . You should talk to your doctor before stop ping to take FYLREVY .

39 If you need to have surgery If you are going to have surgery, tell the surgeon that you are taking FYLREVY . You may need to stop taking FYLREVY about 4 to 6 weeks before the operation to reduce the risk of a blood clot (see section 2, Blood clots in a vein). Ask your doctor when you can start taking FYLREVY again.

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 .

The following diseases are reported more often in women using HRT compared to women not using HRT:

• breast cancer;
• abnormal growth or cancer of the lining of the womb (endomethrial hyperplasia or cancer);
• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolism);
• heart disease;
• stroke;
• probable memory loss if HRT is started over the age of 65.

There is no experience with estetrol -containing HRT .

For more information about these side effects, see section 2.

The following side effects have been reported while using FYLREVY :

Very common (may affect more than 1 in 10 people)

• vaginal bleeding ;
• thickening of the lining of the womb (endometrial thickening) ;

Common (may affect up to 1 in 10 people)

• vaginal fungal infection (candidiasis) ;
• non-cancerous growth of the womb (uterine leiomyoma) ;
• dizziness ;
• lower belly ( abdominal ) pain,
• belly ( abdominal ) pain ;
• bloating;
• feeling sick (nausea) ;
• constipation
• pain in arms or legs (pain in extremity);
• abnormal growth of the lining of the womb (disordered proliferative endometrium) ;
• pain in the brea sts;
• tender breasts ;
• pain in the nipples ;
• contractions of the womb;
• vaginal discharge;
• itchy vulva or vagina (vulvovaginal pruritus)
• extreme tiredness (asthenia) ;
• increase in weight .

Uncommon (may affect up to 1 in 100 people)

• harm ful blood clots in a vein for example o in a leg or foot (deep vein thrombosis) o in a lung (i.e. pulmonary embolism)
• itchy skin rash (urticaria) ;

40 • excessive thickening of the lining of the womb (endometrial hyperplasia) ;

• polyps (smal l growths) in the womb ;
• the lining of the womb (endometrium) growing into the muscle layer of the womb (adenomyosis);
• lump in the breast s;
• swollen breasts ;
• sac of fluid within the ovaries (ovarian cyst) ;
• swelling in arms or legs (peripheral swelling ).

The following side effects have been reported with other HRTs:

• gall bladder disease ;
• various skin disorders:
• discoloration of the skin especially of the face or neck known as “pregnancy patches” (chloasma);
• painful reddish skin nodules (erythema nodosum);
• rash with target -shaped reddening or sores (erythema multiforme).

Reporting of side effects

If you get any side effects, talk to your doctor , pharmacist or nurse . This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V . By reporting side effects you can help provide more information on the safety of this medicine.

🌡️ 5. How to store FYLREVY

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 blister and carton after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

📦 6. Contents of the pack and other information

What FYLREVY contains

• The active substance is estetrol .

FYLREVY 14.2 mg film -coated tablets Each film -coated tablet contains 14.2 mg estetrol (as estetrol monohydrate) .

FYLREVY 18.9 mg film -coated tablets Each film -coated tablet contains 18.9 mg estetrol (as estetrol monohydrate) .

• The other ingredients are:

Tablet core : Lactose monohydrate, sodium starch glycolate (see section 2, ‘ FYLREVY contains lactose and sodium’) , maize starch, povidone K30 , magnesium stearate ( E572).

Tablet coating : Hypromellose (E464), hydroxypropylcellulose (E463), talc (E553b), c ottonseed oil, hydrogenated, titanium dioxide (E171), iron oxide yellow (E172), iron oxide red (E172).

What FYLREVY looks like and contents of the pack

FYLREVY 14.2 mg film -coated tablets 41 The film -coated tablets are orange, 6 mm diameter, round, biconvex with a drop- shaped debossing on one side.

FYLREVY 18.9 mg film -coated tablets The film -coated tablets are yellow, 6 mm diameter, round, biconvex with a drop- shaped debossing on one side.

FYLREVY is presented in transparent PVC/aluminium blisters of 28 film-coated tablets packed in a carton with a n etui storage case.

Pack sizes: 28 , 84 or 168 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Gedeon Richter Plc.

Gyömrői út 19- 21.

1103 Budapest Hungary

Manufacturer

Gedeon Richter Plc.

Gyömrői út 19- 21 1103 Budapest Hungary Haupt Pharma Münster GmbH Schleebrüggenkamp 15 48159 Münster Germany

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site: https://www.ema.europa.eu .

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information FYLREVY (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/26/2020).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.