Ovestin

Leaflet accompanying the packaging: information for the user

Ovestin, 2 mg, tablets

Estriol

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

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

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

1. What is Ovestin and what is it used for

Ovestin is used as part of hormone replacement therapy (HRT). The medicine contains the female sex hormone estriol (estrogen). Ovestin is used in women after menopause, at least 12 months after the natural menstrual cycle has stopped. Ovestin is used to alleviate symptoms that occur after menopause. During menopause, the amount of estrogen produced by the woman's body gradually decreases. If the ovaries are surgically removed (a procedure called oophorectomy) before menopause, estrogen production decreases very quickly. In many cases, the decrease in estrogen levels in the body leads to the occurrence of menopausal symptoms, such as hot flashes or night sweats. Estrogen deficiency can cause dryness and increased sensitivity of the vaginal walls, which is the cause of painful intercourse and the occurrence of inflammatory conditions and severe itching of the vagina. Estrogen deficiency can also cause symptoms of urinary incontinence and recurrent urinary tract infections. Ovestin alleviates symptoms that occur after menopause. Improvement may only be noticeable after a few days or even weeks. Ovestin is only recommended by a doctor if the symptoms seriously disrupt the patient's daily life. In addition to the above indications, Ovestin may also be used for:

• treatment of certain forms of infertility
• acceleration of wound healing after surgical operations in postmenopausal women undergoing vaginal surgery
• accurate assessment of cervical smears in postmenopausal women.

2. Important information before taking Ovestin

Medical history and regular check-ups

Taking HRT is associated with a risk that should be considered when deciding to start or continue hormone replacement therapy. The experience with treating women who have premature menopause (due to ovarian failure or after surgery) is limited. In women with premature menopause, the risk associated with HRT may vary. You should always consult a doctor. Before starting (or resuming) HRT, the doctor will take a medical history of the patient and any diseases that occur in the family. They may also decide to perform a physical examination, including a breast examination and/or gynecological examination through the vagina, if necessary. After starting Ovestin, you should regularly visit your doctor for check-ups (at least once a year). During the check-up, you should discuss the benefits and risks associated with continuing to take Ovestin with your doctor. You should regularly perform breast exams as recommended by your doctor.

When not to take Ovestin:

Ovestin should not be taken if any of the following situations apply to the patient. If in doubt, consult your doctor before taking Ovestin. When not to take Ovestin:

If any of the above health conditions occur for the first time while taking Ovestin, you should stop taking it and contact your doctor immediately.

Warnings and precautions

Before starting treatment, inform your doctor if any of the following conditions are currently present or have occurred in the past, as they may recur or worsen during Ovestin treatment. If this happens, you should visit your doctor more often:

• uterine fibroids (leiomyoma)
• growth of cells lining the uterus (endometriosis) or a history of excessive growth of the uterine lining (endometrial hyperplasia)
• increased risk of blood clots [see "Blood clots in veins (venous thrombosis)"]
• increased risk of estrogen-dependent tumors (such as breast cancer in the mother, sister, or grandmother)
• high blood pressure
• liver disorders, such as benign liver tumors
• diabetes with or without vascular complications
• gallstones
• migraine or severe headaches
• immune system disease affecting multiple internal organs (systemic lupus erythematosus - SLE, a chronic disease of the connective tissue with skin changes throughout the body)
• epilepsy
• asthma
• disease affecting the eardrum and causing hearing loss (otosclerosis)
• fluid retention in the body due to heart or kidney disease
• hereditary and acquired angioedema.

Stop taking Ovestin and contact your doctor immediatelyif any of the following symptoms occur while taking HRT:

• any of the conditions listed in "When not to take Ovestin"
• yellowing of the skin and whites of the eyes (jaundice), which may be a sign of liver disease
• swelling of the face, tongue, and/or throat, and/or difficulty swallowing or hives with difficulty breathing, which suggest angioedema
• significant increase in blood pressure (possible symptoms include headache, fatigue, dizziness)
• migraine-like headaches that occur for the first time
• pregnancy
• symptoms indicating the formation of blood clots, such as:
• painful swelling and redness of the legs
• sudden chest pain
• difficulty breathing. More information is provided in "Blood clots in veins (venous thrombosis)".

Note:Ovestin 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 contraception. You should consult your doctor.

HRT and tumors

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

Taking only estrogen HRT increases the risk of excessive thickening of the uterine lining (endometrial hyperplasia) and uterine lining cancer (endometrial cancer). This additional risk is protected against by taking a medicine that contains estrogen and a progestogen at the same time for at least 12 days of each 28-day menstrual cycle. Therefore, if the patient has a uterus, the doctor will prescribe a progestogen separately. If the patient has had a hysterectomy (removal of the uterus), they should discuss with their doctor whether they can safely take this medicine without a progestogen. Among women with a uterus who do not take HRT, endometrial cancer is diagnosed in approximately 5 out of 1000 women between the ages of 50 and 65. Among women with a uterus between the ages of 50 and 65 who take only estrogen HRT, endometrial cancer is diagnosed in 10-60 out of 1000 women (i.e., 5-55 additional cases), depending on the dose and duration of treatment. One epidemiological study found that long-term oral administration of small doses of estriol may increase the risk of endometrial cancer. This risk increases with the duration of treatment and disappears within a year after treatment is stopped. Tumors diagnosed in women taking estriol were less advanced clinically than in women not taking estriol. To reduce the risk of endometrial stimulation, the maximum daily dose should not be exceeded, and the maximum daily dose should not be taken for more than a few weeks. In the case of long-term use, the doctor may perform a control examination of the uterus or alternatively prescribe a progestogen.

Irregular bleeding

During the first 3-6 months of taking Ovestin, irregular bleeding or spotting may occur. However, if irregular bleeding:

• persists after the first 6 months of treatment,
• occurs after a period of more than 6 months after starting Ovestin,
• persists after stopping Ovestin, you should contact your doctor, who will decide whether these symptoms require further examination.

Breast cancer

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

Regular breast exams should be performed and a doctor should be consulted if any changes are noticed, such as:

• skin dimpling
• nipple changes
• any visible or palpable lumps.

In addition, it is recommended to perform screening mammograms. When performing screening mammograms, it is essential to inform the nurse or medical staff that you are taking HRT, as this medicine may increase breast density, which can affect the mammogram results. In the case of increased breast density, the mammogram may not detect all lumps. It is not known whether taking Ovestin is associated with the same increased risk of breast cancer as taking other HRT medicines. People concerned about the risk of breast cancer should discuss the benefits and risks of such treatment with their doctor.

Ovarian cancer

Ovarian cancer is rare - much rarer than breast cancer. Taking only estrogen HRT or combined estrogen-progestogen HRT 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 in approximately 2 out of 2000 women over a 5-year period. In women who took HRT for 5 years, ovarian cancer occurs in approximately 3 out of 2000 women (i.e., 1 additional case). It is not known whether taking Ovestin is associated with the same increased risk as taking other HRT medicines.

Effect of HRT on the heart or circulatory system

Blood clots in veins (venous thrombosis)

The risk of blood clots in veins is approximately 1.3-3 times higher in women taking HRT than in those not taking HRT, especially in the first year of treatment. The formation of blood clots can have serious consequences and can cause chest pain, shortness of breath, fainting, or even death if it reaches the lungs. The likelihood of blood clots in veins increases with age and in the following situations. If any of the following situations apply to you, inform your doctor:

• prolonged immobilization due to major surgery, injury, or illness (see also section 3 "Need for surgery")
• significant obesity (body mass index over 30 kg/m²)
• blood clotting disorders that require long-term use of anticoagulant medications
• venous thrombosis in the legs or lungs or other organs in a close relative
• systemic lupus erythematosus (SLE; a chronic disease of the connective tissue with skin changes throughout the body)
• cancer.

Symptoms of venous thrombosis are listed in "Stop taking Ovestin and contact your doctor immediately". ComparisonIn women around the age of 50 who do not take HRT, venous thrombosis can be expected to occur in approximately 4-7 out of 1000 women over a 5-year period. In women around the age of 50 who take combined estrogen-progestogen HRT, the number of cases will be 9-12 out of 1000 women over a 5-year period (i.e., 5 additional cases). In women around the age of 50 who have had a hysterectomy and take only estrogen HRT for more than 5 years, the number of cases will be 5-8 out of 1000 women (i.e., 1 additional case). It is not known whether taking Ovestin is associated with the same increased risk as taking other HRT medicines.

Heart disease (heart attack)

There is no evidence that HRT prevents heart attacks. In women over 60 years old who take combined estrogen-progestogen HRT, the risk of heart disease is slightly higher than in women not taking HRT. In women who have had a hysterectomy and take only estrogen HRT, the risk of heart disease is not increased.

Stroke

The risk of stroke is approximately 1.5 times higher in women taking HRT than in those not taking HRT. The number of additional stroke cases associated with HRT increases with age. ComparisonIn women over 50 years old who do not take HRT, stroke can be expected to occur in approximately 8 out of 1000 women over a 5-year period, and in women of the same age taking HRT, the rate is 11 cases per 1000 women over a 5-year period (i.e., 3 additional cases).

Other conditions

HRT will not prevent memory loss. Some evidence suggests a higher risk of memory loss in women who start HRT after the age of 65. You should consult your doctor about this.

Ovestin and other medicines

Certain medicines may affect the action of Ovestin, which can lead to irregular bleeding. These include:

• antiepileptic drugs (such as phenobarbital, phenytoin, and carbamazepine)
• medicines used to treat tuberculosis (such as rifampicin, rifabutin)
• medicines used to treat HIV (such as nevirapine, efavirenz, ritonavir, and nelfinavir)
• herbal products containing St. John's wort (Hypericum perforatum)

HRT may affect the action of other medicines:

• the antiepileptic drug lamotrigine, as it may increase the frequency of seizures
• medicines used to treat hepatitis C (such as the treatment regimen with ombitasvir/paritaprevir/ritonavir with or without dasabuvir, and the treatment regimen with glecaprevir/pibrentasvir) may cause increased liver enzyme levels in blood tests (increased ALT activity) in women taking combined hormonal contraceptives containing ethinyl estradiol. Ovestin contains estradiol instead of ethinyl estradiol. It is not known whether increased ALT activity may occur when taking Ovestin with such a hepatitis C treatment regimen.

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take, including those available without a prescription, herbal medicines, and other natural products. Your doctor will provide you with appropriate instructions.

Lab tests

If lab tests are necessary, inform your doctor or lab staff that you are taking Ovestin, as it may affect the results of some tests.

Ovestin with food and drink

Food and drink do not affect treatment with Ovestin.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a baby, consult your doctor or pharmacist before taking this medicine. Ovestin is intended for use only in postmenopausal women. If you become pregnant, stop taking Ovestin and consult your doctor. Women who are breastfeeding should consult their doctor before taking Ovestin.

Driving and using machines

Taking Ovestin should not affect your ability to drive or use machines. However, individual reactions to the medicine may vary.

Ovestin contains lactose

If you have been diagnosed with an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to take Ovestin

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, consult your doctor or pharmacist. In the case of menopausal symptoms, the dose is usually 4-8 mg per day for the first few weeks of treatment; then the daily dose should be gradually reduced, e.g., to 1-2 mg per day. In the case of treatment of certain forms of infertility, the dose is usually 1-2 mg per day during the period from the 6th to the 15th day of the menstrual cycle. The optimal dose may vary from patient to patient. To improve wound healing in postmenopausal women undergoing vaginal surgery, 4-8 mg per day is usually taken for 2 weeks before surgery and 1-2 mg per day for 2 weeks after surgery. To facilitate the interpretation of cervical smear results in postmenopausal women, 2-4 mg per day is usually taken for 7 days in the week preceding the smear. The break line on the tablet is only to facilitate breaking the tablet to make it easier to swallow. The tablets should be taken with a sufficient amount of water or other liquid. The medicine should be taken regularly, every day at the same time. Do not divide the doses. Your doctor will try to prescribe the lowest dose that should be taken for the shortest time necessary to alleviate the symptoms. If you feel that the action of Ovestin is too strong or too weak, consult your doctor.

Taking a higher dose of Ovestin than recommended

If you have taken more than the recommended dose of Ovestin, consult your doctor or pharmacist immediately. Taking a higher dose of Ovestin than recommended is not a threat to health and life. However, inform your doctor. Symptoms of overdose are usually nausea and vomiting; in women, bleeding from the genital tract may also occur after a few days.

Missing a dose of Ovestin

Do not take a double dose to make up for a missed dose. If you miss a tablet, take it as soon as possible, if the break in taking tablets is not longer than 12 hours. If the break is longer than 12 hours, skip the missed tablet and take the next tablets according to the previously established schedule.

Need for surgery

Patients who are to undergo surgery should inform their surgeon that they are taking Ovestin. It may be necessary to stop taking Ovestin about 4-6 weeks before surgery to reduce the risk of blood clots (see section 2 "Blood clots in veins"). Ask your doctor when you can start taking Ovestin again. If you have any further doubts about taking this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Ovestin can cause side effects, although not everybody gets them. The following diseases are reported more frequently in women taking HRT than in women not taking HRT:

• breast cancer
• abnormal growth or tumors of the uterine lining (hyperplasia or endometrial cancer)
• ovarian cancer
• blood clots in veins (venous thromboembolism)
• heart disease
• stroke
• possible memory loss, if HRT is started after the age of 65.

More information about these side effects can be found in section 2. Depending on the doses used and the patient's sensitivity, the following side effects may occur:

• breast swelling and tenderness
• mild vaginal bleeding
• increased vaginal discharge
• nausea
• fluid retention in tissues, usually manifesting as swelling of the ankles or feet
• flu-like symptoms

Most patients experience these symptoms during the first few weeks of treatment, and they usually disappear. The following side effects have been reported during the use of other HRT medicines:

• inflammation of the gallbladder
• various skin disorders
• skin discoloration, especially on the face or neck, known as "pregnancy spots" (chloasma)
• painful red lumps on the skin (erythema nodosum)
• rash with circular redness or ulcers (erythema multiforme)

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, 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 Ovestin

Keep this medicine out of the sight and reach of children. Store in a temperature between 2°C and 30°C. Protect from light and moisture. Do not use this medicine after the expiry date stated on the packaging after "Expiry Date" and on the blister after "EXP".

6. Contents of the packaging and other information

What Ovestin contains

• The active substance of Ovestin is estriol. One tablet contains 2 mg of estriol.
• The other ingredients are: colloidal anhydrous silica, magnesium stearate, potato starch, and lactose monohydrate.

What Ovestin looks like and contents of the pack

Ovestin is a white, round, flat tablet with a beveled edge, scored on one side. Each tablet has the marking "DG" above the score and "8" below the score. The medicine is available in PVC/Al blisters in a cardboard box. Pack size: 1 blister of 30 tablets.

Marketing authorization holder

Aspen Pharma Trading Limited 3016 Lake Drive Citywest Business Campus Dublin 24, Ireland tel: +48 22 104 21 00

Manufacturer

Cyndea Pharma Polígono Industrial Emiliano Revilla Sanz Avendia de Ágreda 31 42110 Ólvega (Soria) Spain

Date of last revision of the leaflet: