FEMOSTON

Patient Information Leaflet

Warning! Keep this leaflet! Information on the immediate packaging is in a foreign language.
Femoston (Femoston 2/10)
2 mg (brick-red), 2 mg + 10 mg (yellow), coated tablets
Estradiol, Estradiol + Dydrogesterone
Femoston and Femoston 2/10 are different brand names for the same medicine.
Please read this leaflet carefully before taking the medicine, as it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents

1. What Femoston is and what it is used for
2. Important information before taking Femoston
3. How to take Femoston
4. Possible side effects
5. How to store Femoston
6. Contents of the pack and other information

1. What Femoston is and what it is used for

Femoston is a medication used in Hormone Replacement Therapy (HRT). It contains two types of female hormones: an oestrogen called estradiol and a progestagen called dydrogesterone.
Femoston is indicated for use in women who have symptoms of deficiency in female sex hormones (oestrogens) and in whom at least 6 months have passed since the last menstrual period.
Femoston is used for the following purposes:
Treatment of postmenopausal symptoms
During menopause, the amount of oestrogens produced by a woman's body decreases. This may lead to symptoms such as hot flushes affecting the face, neck, and chest. Femoston relieves symptoms occurring in postmenopausal women. Femoston is prescribed when these symptoms significantly interfere with daily life.
Prevention of osteoporosis
Some postmenopausal women may develop brittle bones (osteoporosis). All available treatment options should be discussed with the doctor.
In cases of increased risk of fractures due to osteoporosis and when the patient cannot take other medications, Femoston may be used to prevent osteoporosis in postmenopausal women.

2. Important information before using Femoston

Medical history and regular check-ups
HRT carries risks that should be considered when deciding whether to start or continue treatment.
Experience with treating women with premature menopause (due to ovarian dysfunction or after surgical removal of ovaries) is limited. In cases of premature menopause, the risks of HRT may differ. Consult your doctor.
Before starting (or restarting) HRT, your doctor should take a full medical history, including family history. Your doctor may decide to carry out additional tests, including breast examination and/or gynaecological examination, if considered necessary.
After starting Femoston, you should have regular check-ups with your doctor (at least once a year). During these visits, you and your doctor should discuss together the benefits and risks of continuing Femoston treatment.
You should undergo regular breast screening according to your doctor's recommendations.

DO NOT take Femoston if any of the following symptoms or medical conditions are present or have occurred previously. If you are uncertain about any of the conditions listed below before taking Femoston, you should contact your doctor.

When not to take Femoston

• if you have been diagnosed with, have had previously, or your doctor suspects breast cancer
• if you have or your doctor suspects the presence of a tumour dependent on oestrogens, e.g. endometrial cancer (cancer of the endometrium)
• if you have or your doctor suspects the presence of a tumour dependent on progestogens
• if you have meningioma or have ever been diagnosed with meningioma (usually a benign tumour of the membrane between the brain and skull)
• if you have vaginal bleeding of unknown cause
• if you have untreated abnormal thickening of the endometrium (endometrial hyperplasia)
• if you have or have had blood clots in the veins (thrombosis), e.g. in the legs (deep vein thrombosis) or lungs (pulmonary embolism)
• if you have a blood clotting disorder (such as protein C deficiency, protein S deficiency or antithrombin deficiency)
• if you have or recently had a disease caused by blood clots in the arteries, e.g. heart attack, stroke or coronary heart disease
• if you have or have had liver disease and liver function test results have not returned to normal
• if you have a rare inherited blood disorder called porphyria
• if you are allergic (hypersensitive) to estradiol, dydrogesterone or any of the other ingredients of Femoston (listed in section 6).

If any of the above conditions occur for the first time while taking Femoston, you must stop taking it immediately and consult your doctor.

Warnings and precautions
Before starting treatment, inform your doctor if you have ever had any of the following conditions, as they may recur or worsen during treatment with Femoston. If you have ever had any of the conditions listed below, you should have more frequent medical check-ups:

• uterine fibroids
• presence of endometrial tissue outside the uterus (endometriosis) or history of abnormal thickening of the endometrium (endometrial hyperplasia)
• presence of risk factors for blood clots (see "Blood clots in the veins (thrombosis)")
• increased risk of oestrogen-dependent cancer (e.g. family history of breast cancer in mother, sister or grandmother)
• high blood pressure
• liver diseases, such as benign liver tumours
• diabetes
• gallstones
• migraine or severe headaches
• autoimmune disease affecting multiple organs (systemic lupus erythematosus)
• epilepsy
• asthma
• ear disease damaging the eardrum and impairing hearing (otosclerosis)
• very high levels of fats in the blood (triglycerides)
• fluid retention due to heart or kidney disorders
• hereditary or acquired angioedema.

You must stop taking Femoston and contact your doctor immediately if you notice any of the following symptoms while using HRT:

• any of the conditions listed under "When not to take Femoston"
• yellowing of the skin or whites of the eyes (jaundice) – these may be signs of liver disease
• swelling of the face, tongue and/or throat and/or difficulty swallowing or hives, combined with breathing difficulties – these may be symptoms of angioedema
• significant increase in blood pressure (symptoms may include: headaches, fatigue, dizziness)
• migraine-type headaches occurring for the first time
• pregnancy
• symptoms of blood clots such as: painful swelling and redness of the legs, sudden chest pain, difficulty breathing. See more information under "Blood clots in the veins (thrombosis)".

Note: Femoston does not have contraceptive effects. If less than 12 months have passed since your last menstrual period and you are under 50 years of age, additional contraception may be necessary to prevent pregnancy. Consult your doctor.

HRT and cancer

Overgrowth of the endometrium (endometrial hyperplasia) and endometrial cancer
Using HRT with oestrogen alone increases the risk of abnormal thickening of the endometrium (endometrial hyperplasia) and endometrial cancer. The progestogen contained in Femoston protects against this additional risk.

Unexpected bleeding
While taking Femoston, you will have a monthly bleed (withdrawal bleeding). However, if in addition to monthly bleeding, unexpected bleeding or spotting occurs which:

• persists for longer than the first 6 months of treatment
• starts after 6 months of taking Femoston
• continues after stopping Femoston
  you should contact your doctor as soon as possible.

Breast cancer
Evidence confirms that taking hormone replacement therapy (HRT), either oestrogen-progestogen combination or oestrogen alone, increases the risk of developing breast cancer. The additional risk depends on how long HRT is used. This additional risk becomes apparent after 3 years of HRT use. After stopping HRT, the additional risk gradually decreases, but the risk may persist for 10 years or longer if HRT was used for more than 5 years.

Comparison
Among women aged 50 to 54 years who do not use HRT, breast cancer will be diagnosed in an average of 13 to 17 out of 1,000 women over a 5-year period.
Among women aged 50 who start a 5-year course of oestrogen-only HRT, the number of cases will be 16–17 per 1,000 women (i.e. 0 to ̄3 additional cases).
Among women aged 50 who start a 5-year course of oestrogen-progestogen HRT, the number of cases will be 21 per 1,000 women (i.e. 4 to 8 additional cases).
Among women aged 50 to 59 who do not use HRT, breast cancer will be diagnosed in an average of 27 out of 1,000 women over a 10-year period.
Among women aged 50 who start a 10-year course of oestrogen-only HRT, the number of cases will be 34 per 1,000 women (i.e. 7 additional cases).
Among women aged 50 who start a 10-year course of oestrogen-progestogen HRT, the number of cases will be 48 per 1,000 women (i.e. 21 additional cases).

• You should regularly examine your breasts. Contact your doctor if you notice any changes such as:
• skin indentation of the breast
• changes around the nipple
• any visible or palpable lumps

Ovarian cancer
Ovarian cancer is rare – significantly less common than breast cancer. Using HRT containing oestrogen alone or oestrogen-progestogen combination is associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer depends on age. For example, among women aged 50 to 54 who do not use HRT, ovarian cancer will be diagnosed in about 2 out of 2,000 women over a 5-year period. Among women who have used HRT for 5 years, it will occur in about 3 out of 2,000 women (i.e. about 1 additional case).

Effects of HRT on the heart and circulation

Blood clots in the veins (thrombosis)
The risk of blood clots in the veins is 1.3 to 3 times higher in women using HRT than in those not using it, especially during the first year of use.
Blood clots can have serious consequences. If they travel to the lungs, they may cause chest pain, breathlessness, fainting or even death.
The risk of venous blood clots increases with age and if any of the following conditions apply. Inform your doctor if you have any of the following:

• inability to walk for a prolonged period due to major surgery, injury or illness (see also section 3 "Planned surgery")
• you are significantly overweight (BMI > 30 kg/m²)
• you have any blood clotting disorders requiring long-term anticoagulant treatment
• any close relatives have ever had blood clots in the legs, lungs or other organs
• you have systemic lupus erythematosus
• you have cancer.

Symptoms of blood clots are described under "You must stop taking Femoston and contact your doctor immediately".

Comparison
Among women aged 50–60 who do not use HRT, venous blood clots are expected in an average of 4 to 7 out of 1,000 over 5 years.
Among women aged 50–60 who use oestrogen-progestogen HRT for more than 5 years, there will be 9 to 12 cases per 1,000 women (i.e. 5 additional cases).

Heart disease (heart attack)
There is no evidence that HRT prevents heart attacks.
In women over 60 years of age using oestrogen-progestogen HRT, there is a slightly higher tendency to develop heart disease compared to women not using HRT.

Stroke
The risk of stroke is about 1.5 times higher in women using HRT than in those not using it. The number of additional stroke cases due to HRT use increases with age.

Comparison
Among women aged 50 to 60 who do not use HRT, stroke is expected in an average of 8 out of 1,000 over 5 years. Among women aged 50 to 60 who use HRT for more than 5 years, there will be 11 cases per 1,000 women (i.e. 3 additional cases).

Meningioma
Using Femoston is associated with the development of usually benign tumours of the tissue layer between the brain and skull (meningioma). If meningioma is diagnosed, your doctor will discontinue treatment with Femoston (see section "When not to take Femoston"). If you notice any symptoms such as vision disturbances (e.g. double or blurred vision), hearing loss or ringing in the ears, loss of smell, worsening headaches, memory loss, seizures, or weakness in arms or legs, you should inform your doctor immediately.

Other conditions
HRT does not prevent memory loss. There is evidence of increased risk of memory loss in women who start HRT after the age of 65. Consult your doctor.

Children
Femoston is indicated only for women with symptoms of oestrogen deficiency who have had at least 6 months since their last menstrual period.

Femoston and other medicines
Some medicines may affect the action of Femoston, which may cause irregular bleeding. These include:

The following medicines may reduce the effectiveness of Femoston, leading to bleeding or spotting:

• antiepileptic drugs (e.g. phenobarbital, carbamazepine, phenytoin)
• tuberculosis medicines (e.g. rifampicin, rifabutin)
• HIV (AIDS) medicines (e.g. nevirapine, efavirenz, ritonavir and nelfinavir)
• herbal remedies containing St John's wort (Hypericum perforatum)

HRT may affect the action of other medicines:

• the antiepileptic drug lamotrigine, as it may increase seizure frequency
• combination treatment regimens for hepatitis C virus (HCV) infection using ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir (see section 4.4) may increase liver function test parameters in blood (elevated liver enzyme AlAT activity) in women using combined hormonal contraceptives containing ethinylestradiol. Femoston contains estradiol instead of ethinylestradiol. It is not known whether elevated AlAT enzyme activity may occur when Femoston is used concomitantly with such HCV combination therapies.

During treatment with Femoston, dangerously high blood levels may occur with the following medicines:

• tacrolimus, cyclosporine – used e.g. after organ transplantation
• fentanyl – a painkiller
• theophylline – used in asthma and other breathing problems.

Therefore, careful monitoring of drug levels may be necessary for a period of time, and dose reduction of the affected medicine may be required.

You should inform your doctor or pharmacist about all other medicines you are currently taking or have recently taken, including medicines available without a prescription, herbal medicines or other natural remedies (e.g. dietary supplements). Your doctor will provide appropriate advice.

Blood tests
Before any planned blood test, inform your doctor or laboratory staff that you are taking Femoston, as this medicine may affect the results of certain laboratory tests.

Femoston with food and drink
Femoston can be taken with or without food.

Pregnancy and breastfeeding
Femoston is indicated only for women with symptoms of oestrogen deficiency who have had at least 6 months since their last menstrual period.

• If pregnancy occurs, stop taking Femoston and contact your doctor. Femoston is not indicated during breastfeeding.

Driving and using machines
No studies on the effect of Femoston on driving and using machines have been conducted. Such an effect is unlikely.

Femoston contains monohydrate lactose.
If you have previously been diagnosed with intolerance to certain sugars, you should contact your doctor before taking this medicine.

3. How to take Femoston

This medicine should always be taken as prescribed by your doctor. If you have any doubts, please
consult your doctor or pharmacist.
When to start taking Femoston
Do not start treatment with Femoston before at least 6 months have passed since your last natural
menstrual period.
Treatment with Femoston may be started on any day if:

• you are not currently using any hormone replacement therapy (HRT), or
• you are switching from another HRT product used in a "continuous combined" regimen. This regimen involves taking a tablet or applying a patch daily that contains both an estrogen and a progestagen.

Treatment with Femoston may be started the day after completion of a 28-day menstrual cycle if:

• you are switching from an HRT regimen used in a "cyclical" or "sequential" regimen. This regimen involves taking a tablet or applying a patch containing estrogen only during the first part of the cycle, followed by taking a tablet or applying a patch containing both estrogen and a progestagen for the next 14 days.

How to take Femoston

• Swallow the tablet with water.
• Tablets may be taken with or without food.
• Try to take the tablet at the same time each day. This helps maintain a constant level of medicine in your body and may help you remember to take it.
• Take one tablet every day without interruption between packs. The blister pack is marked with days of the week to help you remember when to take each tablet (see the translation of weekday symbols located next to each tablet on the immediate packaging – provided at the end of this leaflet and on the sachet included in the package).

Dosage

• Your doctor will prescribe the lowest effective dose for the shortest duration necessary to treat your symptoms. Consult your doctor if the dose seems too strong or too weak for you.
• If Femoston is being taken to prevent osteoporosis, your doctor will adjust the dose according to your individual needs, based on your bone mass.
• Take one brick-red tablet daily for the first 14 days, followed by one yellow tablet daily for the next 14 days. The 28-day treatment schedule is shown on the blister pack (see also the translation of weekday symbols located next to each tablet on the immediate packaging – provided at the end of this leaflet and on the sachet included in the package).

Planned surgery

• If you are scheduled for surgery, inform your surgeon that you are taking Femoston. You may need to stop taking Femoston approximately 4 to 6 weeks before surgery to reduce the risk of blood clots (see section 2 "Blood clots in the veins (venous thromboembolism)"). Ask your doctor when you can resume taking Femoston.

If you take more Femoston than you should
If you (or someone else) take too many Femoston tablets, it is unlikely to cause harmful effects.
Possible symptoms include nausea, vomiting, breast tenderness or pain, dizziness, abdominal pain,
drowsiness/fatigue, or withdrawal bleeding. No additional treatment is usually required, but if you
have any concerns, consult your doctor.

If you miss a dose of Femoston
Take the missed tablet as soon as possible. If more than 12 hours have passed since the tablet should
have been taken, take the next tablet at your usual time and do not take the missed tablet. Do not
take a double dose to make up for a missed dose. Breakthrough bleeding or spotting may occur.

Stopping Femoston
Do not stop taking Femoston without consulting your doctor.

• If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The following conditions have been reported more frequently in women using hormone replacement therapy (HRT) compared to women not using HRT:

• breast cancer
• abnormal growth or cancer of the uterine lining (endometrial hyperplasia or endometrial cancer)
• ovarian cancer
• blood clots in the legs or lungs (venous thromboembolism, pulmonary embolism)
• heart diseases
• stroke
• probable memory loss if HRT is initiated after the age of 65.

For more information on the above adverse effects, see section 2.
The following adverse effects may occur during treatment with Femoston:

Very common (may occur in more than 1 in 10 women):

• headaches
• abdominal pain
• back pain
• breast tenderness or pain

Common (may occur in up to 1 in 10 women):

• vaginal candidiasis (yeast infection of the vagina caused by Candida albicans)
• depression, nervousness
• migraine. If migraine-type headaches occur for the first time, treatment with Femoston should be discontinued immediately and you should contact your doctor without delay
• dizziness
• nausea, vomiting, flatulence (bloating)
• skin allergic reactions (such as rash, severe itching, urticaria)
• bleeding disorders, such as irregular bleeding or spotting, painful menstruation, excessive or scanty bleeding
• pelvic pain
• hot flushes
• feeling of weakness, fatigue, and general malaise
• swelling of ankles, feet, or fingers (peripheral edema)
• weight gain

Uncommon (may occur in up to 1 in 100 women):

• benign growths in the pelvis (e.g. fibroids) may increase in size
• hypersensitivity reactions, such as breathing difficulties (allergic asthma) or other systemic reactions such as nausea, vomiting, diarrhea, or hypotension
• change in libido
• blood clots causing embolism in blood vessels of legs or lungs (venous thromboembolism or pulmonary embolism)
• liver function disorders, sometimes with jaundice, feeling of weakness or general malaise, and abdominal pain. If yellowing of the skin or whites of the eyes occurs, treatment with Femoston should be stopped immediately and you should contact your doctor without delay
• gallbladder disease
• breast swelling (breast edema)
• premenstrual syndrome
• weight loss

Rare (may occur in up to 1 in 1000 women):

• myocardial infarction (heart attack)
• swelling of tissues in the face and neck causing breathing difficulties (angioedema)
• purple spots or lesions on the skin (purpura)

Other adverse effects reported during HRT use, including Femoston, with unknown frequency:

• benign or malignant tumors that may be influenced by estrogen levels, such as endometrial cancer (cancer of the endometrium), ovarian cancer (for more information see section 2)
• increase in size of tumors that may be influenced by progestogen levels (e.g. meningioma)
• disease causing destruction of red blood cells (hemolytic anemia)
• autoimmune disease that may affect multiple organs (systemic lupus erythematosus)
• worsening of epileptic seizures (epilepsy)
• involuntary muscle spasms (chorea)
• arterial blood clots (arterial thrombosis)
• pancreatitis in women with previously existing high levels of certain blood fats (hypertriglyceridemia)
• various skin disorders: skin pigmentation, especially on face and neck known as "pregnancy mask" (melasma), painful red skin nodules (nodular erythema), rash in the form of red rings or blisters (erythema multiforme)
• leg cramps
• urinary incontinence
• painful/lumpy breasts (fibrocystic breast changes)
• cervical erosion
• worsening of symptoms of a rare disease affecting blood pigments (porphyria)
• high levels of certain fats in the blood (hypertriglyceridemia)
• changes in the cornea of the eye (corneal edema), inability to wear contact lenses (contact lens intolerance)
• increased total concentration of thyroid hormones

Reporting of adverse effects
If any adverse effects occur, including those not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can also be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Reporting adverse effects helps to gather more information on the safety of the medicine.

5. How to store Femoston

Keep this medicine out of sight and reach of children.
No special storage instructions apply to this medicinal product.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such measures help protect the environment.

6. Contents of the pack and other information

What Femoston contains

• The active substances are: estradiol (as estradiol hemihydrate) and dydrogesterone
• Each brick-red tablet contains 2 mg of estradiol
• Each yellow tablet contains 2 mg of estradiol and 10 mg of dydrogesterone
• Other ingredients are: monohydrate lactose, hypromellose, corn starch, colloidal anhydrous silica, magnesium stearate.
  Pink coating Opadry OY-6957 (for brick-red tablets): titanium dioxide (E 171), red iron oxide (E 172), black iron oxide (E 172), yellow iron oxide (E 172), hypromellose, polyethylene glycol 400, talc.
  Yellow coating Opadry OY-02B2264 (for yellow tablets): titanium dioxide (E 171), yellow iron oxide (E 172), hypromellose, polyethylene glycol 400, talc.

What Femoston looks like and contents of the pack

• The coated tablets are round, biconvex, with "379" engraved on one side.
• Femoston contains tablets in two colors. Each blister contains 14 brick-red tablets (for the first 14 days of the cycle) and 14 yellow tablets (for the following 14 days of the cycle).
• Each blister contains 28 tablets. The tablets are packed in PVC/Al blisters and placed in a cardboard box. A sachet is included in the packaging, in which the blister should be placed.
• The pack contains either 28 or 84 coated tablets.

For more detailed information, please contact the responsible entity or parallel importer.
Marketing Authorisation Holder in Romania, country of export:
Theramex Ireland Limited
3rd Floor, Kilmore House, Park Lane, Spencer Dock, Dublin 1, Ireland
Manufacturer:
Abbott Biologicals B.V.
Veerweg 12
8121 AA Olst
The Netherlands
Parallel importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw, Poland
Repackaged by:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw, Poland
Marketing Authorisation numbers in Romania, country of export: 15178/2023/01
15178/2023/02
Parallel import authorisation number: 80/18

Translation of the symbols for days of the week printed next to each tablet in the immediate packaging:
Luni – Monday
Mar – Tuesday
Mie – Wednesday
Joi – Thursday
Vin – Friday
Sâm – Saturday
Dum – Sunday