Estrofem mite

PATIENT INFORMATION LEAFLET

PACKAGE LEAFLET: INFORMATION FOR THE USER

Estrofem mite, 1 mg, coated tablets

Estradiol

Read the package leaflet carefully before taking the medicine, as it contains important information for you.

• You should 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 symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents of the package leaflet

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

1. What is Estrofem mite and what is it used for

Estrofem mite is a medicine for hormone replacement therapy (HRT). It contains the female hormone estrogen - estradiol. Estrofem mite is used for women after menopause, especially for women who have had their uterus removed (after a hysterectomy) and therefore do not need to take combined estrogen-progestogen therapy. Estrofem mite is used to:

relieve symptoms occurring after menopause

During menopause, the level of estrogen produced by the body decreases, which can cause symptoms such as hot flashes on the face, neck, and chest. Estrofem mite helps to alleviate these symptoms. Estrofem mite should only be prescribed to a patient when these symptoms seriously disrupt daily life. Experience in treating women over 65 years of age is limited.

2. Important information before taking Estrofem mite

Medical history and regular medical examinations

Taking HRT involves risks that should be considered when a patient decides to start or continue hormone replacement therapy. Experience in treating women with premature menopause (due to ovarian failure or surgery) is limited. If a patient is experiencing premature menopause, the risk associated with HRT may vary. You should talk to your doctor. Before starting (or restarting) HRT, your doctor should take your medical history, including your family history. Your doctor will decide whether to perform tests, including a breast examination and/or a gynecological examination, if necessary. If you decide to take Estrofem mite, you should regularly visit your doctor for check-ups (at least once a year). During these check-ups, you should discuss with your doctor the benefits and risks of taking Estrofem mite. You should also have regular mammograms as recommended by your doctor.

When not to take Estrofem mite

If you have any of the following conditions or if you are unsure, you musttell your doctorbefore taking Estrofem mite. Do not start taking Estrofem mite if:

• you are allergic to estradiol or any of the other ingredients of this medicine (listed in section 6. "Contents of the pack and other information");
• you have been diagnosed with, suspected, or had breast cancer in the past;
• you have been diagnosed with, suspected, or had estrogen-dependent tumors, such as endometrial cancer (cancer of the lining of the uterus);
• you have abnormal vaginal bleeding that has not been diagnosed by a doctor;
• you have excessive growth of the lining of the uterus (endometrial hyperplasia) and it is not being treated;
• you have been diagnosed with or had blood clots in the veins (venous thromboembolism), in the veins of the legs (deep vein thrombosis) or in the lungs (pulmonary embolism);
• you have blood clotting disorders (coagulation disorders with a tendency to form blood clots, such as protein C, protein S, or antithrombin deficiency);
• you have had or have conditions caused by blood clots in the arteries (thromboembolic disorders), such as coronary heart disease or heart attack;
• you have had or have liver disease, and liver function tests have not returned to normal;
• you have a rare, inherited blood disorder called porphyria.

If any of the above conditions occur for the first time while taking Estrofem mite, you should stop taking it and consult your doctor.

Warnings and precautions

Before starting Estrofem mite, you should discuss it with your doctor or pharmacist. Before starting treatment, you should inform your doctor if you currently have or have had any of the following conditions, as they may recur or worsen while taking Estrofem mite. In these cases, your doctor may decide that you need to be closely monitored:

• uterine fibroids (fibroids),
• endometriosis or excessive growth of the uterine lining (endometrial hyperplasia) in your medical history,
• factors that increase the risk of blood clots (see "Blood clots in the veins (venous thromboembolism)"),
• factors that increase the risk of estrogen-dependent tumors (breast cancer in your mother, sister, or grandmother),
• high blood pressure,
• liver disease, such as liver tumors (benign liver tumors),
• diabetes,
• gallstones,
• migraines or severe headaches,
• systemic lupus erythematosus (an autoimmune disease),
• epilepsy,
• asthma,
• otosclerosis (a condition that leads to gradual hearing loss),
• high levels of fats in the blood (triglycerides),
• fluid retention in the body due to heart or kidney failure,
• hereditary and acquired angioedema.

If you experience any of the following conditions while taking HRT, you should stop taking Estrofem mite immediately and consult your doctor:

• if you experience any of the conditions listed in the "When not to take Estrofem mite" section;
• if your skin or the whites of your eyes turn yellow (jaundice) or if you experience liver problems;
• if you experience swelling of the face, tongue, and/or throat, and/or difficulty swallowing or hives, along with difficulty breathing, which may indicate angioedema;
• if you experience a significant increase in blood pressure (symptoms of high blood pressure may include headache, fatigue, dizziness);
• if you experience a migraine headache;
• if you become pregnant;
• if you experience signs of a blood clot, such as:
• painful swelling and redness of the legs,
• sudden chest pain,
• difficulty breathing (shortness of breath). For more information, see "Blood clots in the veins (venous thromboembolism)".

Note:Estrofem mite is not a contraceptive. If it has been less than 12 months since your last menstrual period or you are under 50 years old, you may need to use an additional method of birth control. You should talk to your doctor.

HRT and cancer

Excessive growth of the uterine lining (endometrial hyperplasia) and uterine lining cancer (endometrial cancer)

Taking only estrogens in HRT increases the risk of excessive growth of the uterine lining (endometrial hyperplasia) and uterine lining cancer (endometrial cancer). Taking a progestogen in combination with estrogen for at least 12 days of each 28-day cycle protects against this additional risk, so your doctor may prescribe a progestogen for you if you have a uterus. However, if you have had a hysterectomy (uterus removal), you should discuss with your doctor whether taking this medicine without a progestogen is safe. Comparison In women who have a uterus and do not take HRT, endometrial cancer is diagnosed in about 5 out of 1000 women between the ages of 50 and 65. Depending on the duration of treatment and the dose of estrogen taken, in women between the ages of 50 and 65 who have a uterus and take only estrogens in HRT, endometrial cancer is diagnosed in 10 to 60 out of 1000 women (i.e., an additional 5 to 55 cases).

Unexpected bleeding

While taking Estrofem mite, you will experience monthly bleeding (so-called withdrawal bleeding). However, if you experience unexpected bleeding or spotting between monthly bleedings, which:

• lasts longer than the first 6 months,
• occurs after taking Estrofem mite for more than 6 months,
• continues after stopping HRT, you should contact your doctor as soon as possible.

Breast cancer

Data confirms that taking hormone replacement therapy (HRT) in the form of combined estrogen and progestogen or estrogen alone increases the risk of breast cancer. The additional risk depends on how long you take HRT. This additional risk becomes apparent after 3 years of HRT. After stopping HRT, the additional risk will decrease over time, but the risk may persist for 10 years or more if HRT lasted more than 5 years. Comparison In women between the ages of 50 and 54 who do not take HRT, breast cancer is diagnosed in about 13 to 17 out of 1000 women over a 5-year period. In women aged 50 who start 5-year estrogen-only HRT, the number of cases will be 16-17 out of 1000 patients (i.e., 0 to 3 additional cases). In women aged 50 who start 5-year combined estrogen-progestogen HRT, the number of cases will be 21 out of 1000 patients (i.e., 4 to 8 additional cases). In women between the ages of 50 and 59 who do not take HRT, breast cancer is diagnosed in about 27 out of 1000 women over a 10-year period. In women aged 50 who start 10-year estrogen-only HRT, the number of cases will be 34 out of 1000 patients (i.e., 7 additional cases). In women aged 50 who start 10-year combined estrogen-progestogen HRT, the number of cases will be 48 out of 1000 patients (i.e., 21 additional cases).

You should regularly examine your breasts. You should contact your doctor if you notice any changes in your breasts, such as:

• wrinkling of the skin,
• changes in the nipple,
• lumps that can be seen or felt.

In addition, it is recommended to participate in offered breast cancer screening programs. It is important to inform the nurse or medical staff performing the X-ray that you are taking hormone replacement therapy, as this medicine may increase breast density, which can affect the results of the mammogram. Not all lumps can be detected during a mammogram in areas with increased breast density.

Ovarian cancer

Ovarian cancer is rare - much rarer than breast cancer. Taking HRT that includes only estrogens or a combination of estrogens and progestogens is associated with a slightly increased risk of ovarian cancer. The risk of ovarian cancer depends on age. For example, in women between the ages of 50 and 54 who do not take HRT, ovarian cancer is diagnosed over a 5-year period in about 2 out of 2000 women. In women who took HRT for 5 years, it occurs in about 3 out of 2000 women taking it (i.e., about 1 additional case).

Effect of HRT on the heart and blood vessels

Blood clots in the veins (venous thromboembolism)

The risk of developing venous thromboembolismis 1.3 to 3 times higher in women taking HRT compared to those not taking it, especially in the first year of treatment. Blood clots can be life-threatening and if they move to the lungs, they can cause chest pain, shortness of breath, fainting, or even death. In patients with a diagnosed tendency to form blood clots, there is a higher risk of venous thromboembolism, and taking HRT may increase this risk. In these patients, HRT is contraindicated. The risk of blood clots in the veins is higher if you are older and if you have any of the following factors. You should tell your doctor if:

• you are unable to walk for a long time due to extensive surgery, injury, or illness (see also section 3. "If surgery is planned");
• you are obese (body mass index - BMI > 30 kg/m2);
• you have had thromboembolic disorders that required taking medicines to prevent blood clots (anticoagulants);
• you or anyone in your close family has had blood clots in the legs, lungs, or other organs;
• you are pregnant or in the postpartum period;
• you have systemic lupus erythematosus;
• you have been diagnosed with cancer.

Symptoms of a blood clot, see "If you experience any of the following conditions while taking HRT, you should stop taking Estrofem mite immediately and consult your doctor". Comparison In women between the ages of 50 and 59 who do not take HRT, the estimated number of cases of blood clots in the veins over 5 years is 4 to 7 out of 1000 women. In women between the ages of 50 and 59 who take combined estrogen-progestogen HRT, the number of cases of blood clots in the veins over 5 years will be 9 to 12 out of 1000 women (i.e., 5 additional cases). In women between the ages of 50 and 59 with a uterus removed who take only estrogen HRT, the number of cases of blood clots in the veins over 5 years will be 5 to 8 out of 1000 women (i.e., 1 additional case).

Coronary heart disease (heart attack)

There is no evidence that HRT helps prevent heart attacks. In women over 60 years old taking combined estrogen-progestogen HRT, there is a slightly increased risk of developing coronary heart disease compared to women not taking HRT. In women with a uterus removed who take only estrogen HRT, there is no increased risk of developing coronary heart disease.

Stroke

The risk of stroke is about 1.5 times higher in women taking HRT compared to those not taking it. The number of additional cases of stroke caused by HRT increases with age. Comparison In women between the ages of 50 and 59 who do not take HRT, a stroke occurs in about 8 out of 1000 women over 5 years. In women between the ages of 50 and 59 who take HRT, the number of cases of stroke over 5 years will be 11 cases out of 1000 women (i.e., 3 additional cases).

Other conditions

HRT does not improve cognitive function (perception, attention, memory). The risk of memory loss may be slightly higher in women who start HRT at an older age. You should consult your doctor.

Estrofem mite and other medicines

Some medicines may affect the effectiveness of Estrofem mite. This may lead to irregular bleeding. This applies to the following medicines:

• •antiepileptic drugs(e.g., phenobarbital, phenytoin, and carbamazepine),
• •antituberculosis drugs(e.g., rifampicin, rifabutin),
• •HIV drugs(e.g., nevirapine, efavirenz, ritonavir, and nelfinavir),
• •herbal preparations containing St. John's Wort(Hypericum perforatum).

HRT may affect the action of other medicines:

• antiepileptic drug (lamotrigine), which may increase the frequency of seizures;
• drugs used to treat hepatitis C virus (HCV; e.g., combination treatment of ombitasvir/paritaprevir/ritonavir with dasabuvir or without dasabuvir, as well as glecaprevir/pibrentasvir) may cause increased liver blood test results (increased liver enzyme activity) in women taking combined hormonal contraceptives containing ethinyl estradiol. Estrofem mite contains estradiol, not ethinyl estradiol. It is not known whether taking Estrofem mite with this combination HCV treatment regimen may increase liver enzyme activity.

Tell your doctor or pharmacistabout all medicines you are taking, have recently taken, or plan to take (e.g., over-the-counter medicines, herbal medicines, or other natural products). Your doctor will advise you on this.

Estrofem mite with food and drink

Tablets can be taken with or without food and drink.

Pregnancy and breastfeeding

Estrofem mite is intended for use only in women after menopause. If pregnancy is detected during treatment with Estrofem mite, treatment should be stopped immediately and your doctor consulted. Estrofem mite is not indicated during breastfeeding.

Driving and using machines

The effect of Estrofem mite on the ability to drive and use machines is not known.

Estrofem mite contains lactose monohydrate

If you have been diagnosed with intolerance to some sugars, you should contact your doctor before taking Estrofem mite.

Laboratory tests

If a blood test is necessary, you should inform your doctor or laboratory staff that you are taking Estrofem mite, as this medicine may affect the results of some tests.

3. How to take Estrofem mite

This medicine should always be taken exactly as your doctor has told you. If you are unsure, ask your doctor or pharmacist. In women with a uterus removed who are not taking any other hormone therapy, treatment with Estrofem mite can be started on any day.

Take one tablet a day, at the same time every day.

After taking all 28 tablets from the calendar pack, treatment should be continued by starting the next pack, without a break in treatment. Instructions for using the calendar pack can be found at the end of this leaflet, in the section titled "INSTRUCTIONS FOR USE". Your doctor will prescribe the lowest possible dose for you to take for the shortest time necessary to relieve your symptoms. If you think that the dose of Estrofem mite is too high or too low, you should consult your doctor. Women with a uterus removed will not be advised to take an additional progestogen (another female hormone) unless endometriosis (growth of uterine lining tissue outside the uterus) has been diagnosed. If you are currently taking other HRT medicines, you should ask your doctor or pharmacist when you can start taking Estrofem mite. If bleeding or spotting occurs during the cycle, it is not a cause for concern, especially in the early months of HRT (for more information, see also section 2. "HRT and cancer", "Excessive growth of the uterine lining (endometrial hyperplasia) and uterine lining cancer (endometrial cancer)").

Taking more than the prescribed dose of Estrofem mite

If you take more than the prescribed dose of Estrofem mite, you should contact your doctor or pharmacist. Overdose of Estrofem mite may cause nausea or vomiting.

Missing a dose of Estrofem mite

If you forget to take a tablet at the usual time, you should take it within the next 12 hours. If more than 12 hours have passed, do not take the missed dose, but take the next dose at the usual time the next day. Do not take a double dose to make up for the missed dose. Missing a dose may increase the likelihood of bleeding and spotting during the cycle, if you have a uterus.

Stopping Estrofem mite treatment

If you want to stop taking Estrofem mite, you should consult your doctor, who will explain the consequences of stopping treatment and discuss other possible therapies. If you have any further questions about taking this medicine, you should ask your doctor or pharmacist.

If surgery is planned

If you are scheduled for surgery, you should tell the surgeon that you are taking Estrofem mite. It may be necessary to stop taking Estrofem mite 4 to 6 weeks before surgery to minimize the risk of blood clots (see section 2. "Blood clots in the veins (venous thromboembolism)"). Before restarting Estrofem mite, you should consult your doctor.

4. Possible side effects

Like all medicines, Estrofem mite can cause side effects, although not everybody gets them. Women taking HRT are at increased risk of developing the following conditions compared to women not taking HRT:

• breast cancer;
• excessive growth or cancer of the uterine lining (endometrial hyperplasia or cancer);
• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolism);
• coronary heart disease;
• stroke;
• possibly cognitive impairment (perception, attention, memory), if HRT is started at an older age.

For more information, see section 2. "Important information before taking Estrofem mite".

Hypersensitivity and/or allergic reactions (uncommon side effects - may occur in less than 1 in 100 women)

Although hypersensitivity is an uncommon side effect, it can occur. Symptoms of hypersensitivity and/or allergic reactions may include any of the following: hives, itching, swelling, difficulty breathing, low blood pressure (pale and cold skin, rapid heartbeat), dizziness, sweating, which may be signs of anaphylactic reaction and/or anaphylactic shock. If you experience any of these symptoms, you muststop taking Estrofem mite and seek medical attention immediately.

Common (may occur in less than 1 in 10 women)

• depression,
• headache,
• abdominal pain,
• nausea,
• leg cramps,
• breast pain, tenderness, or enlargement,
• peripheral edema (fluid retention),
• weight gain.

Uncommon (may occur in less than 1 in 100 women)

• vision disturbances,
• venous thrombosis,
• heartburn (indigestion),
• vomiting,
• bloating and/or gas,
• gallstones,
• rash or hives.

Rare (may occur in less than 1 in 10,000 women)

• generalized allergic reactions (e.g., anaphylactic reaction, anaphylactic shock),
• irregular vaginal bleeding*,
• worsening of migraines,
• stroke,
• dizziness,
• diarrhea,
• hair loss (alopecia),
• increased blood pressure. * in women with a uterus

Other side effects after taking estrogens

• heart attack, congestive heart failure,
• venous thromboembolism, e.g., deep vein thrombosis of the legs or pelvis and pulmonary embolism,
• gallbladder disease,
• skin and subcutaneous tissue disorders:
• skin discoloration, especially on the face or neck, called "pregnancy spots" (chloasma),
• red, painful lumps (erythema nodosum),
• rash, including ring-shaped, red, and swollen patches (erythema multiforme),
• purpura,
• itching,
• fungal infections of the vagina,
• estrogen-dependent benign and malignant tumors, e.g., endometrial cancer, endometrial hyperplasia, or uterine fibroids*,
• insomnia,
• epilepsy,
• libido disorders,
• worsening of asthma,
• possibly dementia. * in women with a uterus

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, you should tell your doctor or pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety, Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych (Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products): Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Estrofem mite

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 label and carton after "EXP". The expiry date refers to the last day of that month. Store below 25°C. Do not store in a refrigerator. Store in the original package. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Estrofem mite contains

• The active substance is estradiol 1 mg (in the form of estradiol hemihydrate).
• The other ingredients are: lactose monohydrate, cornstarch, hydroxypropyl cellulose, talc, and magnesium stearate.
• The ingredients of the tablet coating are: hypromellose, talc, titanium dioxide (E171), propylene glycol, and red iron oxide (E172).

What Estrofem mite looks like and contents of the pack

The coated tablets are red, round, 6 mm in diameter, and have the code NOVO 282 embossed on one side. Pack sizes:

• 28 coated tablets

Marketing authorization holder and manufacturer

Novo Nordisk A/S Novo Allé 2880 Bagsværd, Denmark

For more information, contact your local representative of the marketing authorization holder:

Novo Nordisk Pharma Sp. z o.o. Tel.: 22 444 49 00 Fax: 22 444 49 01

Date of last revision of the leaflet:

Other sources of information

Detailed information about this medicine can be found on the website of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: www.urpl.gov.pl.

INSTRUCTIONS FOR USE

How to use the calendar pack

1. Setting the day indicator

Turn the inner dial so that the day of the week you start treatment is opposite the opening in the outer part.

2. Removing the first tablet

Break off the tablet cover and remove the first tablet.

3. Next tablets

The next day, turn the transparent part one place clockwise, i.e., in the direction indicated by the arrow. Remove the next tablet. Remember to take one tablet a day.

The transparent part can only be turned after the tablet has been removed from the opening.