Ovestin

Leaflet accompanying the packaging: information for the user

Warning! The leaflet should be kept. Information on the immediate packaging in a foreign language.

Ovestin (Synapause-E)

2 mg, tablets

Estriol
Ovestin and Synapause-E are different trade names for the same medicine.

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet so that you can read it again if necessary.
• In case of any doubts, you should consult a 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, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is Ovestin and what is it used for
• 2. Important information before using Ovestin
• 3. How to use 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 postmenopausal women, at least 12 months after the cessation of natural menstruation.
Ovestin is used to alleviate symptoms that occur after menopause.
During menopause, the amount of estrogen produced in 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 recommended by a doctor only when symptoms seriously disrupt the patient's daily life.
In addition to the above-mentioned use of Ovestin tablets, this medicine can also be used in the following cases:

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

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2. Important information before using Ovestin

Medical history and regular check-ups

The use of HRT is associated with a risk that should be considered when deciding to start or continue therapy.
Experience with the treatment of women who have premature menopause (due to ovarian failure or after surgery) is limited. In women with premature menopause, the risk associated with the use of HRT may be varied. You should always consult a doctor.
Before starting (or resuming) HRT, the doctor will take a medical history of the patient's health and family diseases. 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 of continuing therapy with Ovestin with your doctor.
You should regularly perform breast examinations as recommended by your doctor.

When not to use Ovestin:

Ovestin should not be used if any of the following situations apply to the patient. If in doubt, consult a doctor before using Ovestin.

When not to use Ovestin:

If any of the above health conditions occur for the first time while using Ovestin, treatment should be stopped immediately and a doctor should be consulted without delay.

Warnings and precautions

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Before starting treatment, the doctor should be informed 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 endometrial cells outside 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 (e.g., 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 - a chronic connective tissue disease with skin lesions throughout the body)
• epilepsy
• asthma
• disease affecting the eardrum and causing hearing impairment (otosclerosis)
• fluid retention in the body due to heart or kidney disease.

You should inform your doctor if you have hepatitis C and are being treated with drugs such as ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin. Taking these drugs with some estrogen-containing medications may cause elevated liver function test results (increased ALT enzyme activity); the risk of this happening with Ovestin is currently unknown.
You should tell your doctor if you notice any changes in your condition while using Ovestin.

Stop using Ovestin and consult a doctor immediately

if any of the following conditions occur while using HRT:

• any of the conditions listed in "When not to use Ovestin"
• yellowing of the skin and whites of the eyes (jaundice), which may be a sign of liver disease
• significant increase in blood pressure (which may manifest as 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
• breathing difficulties. 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 the last menstrual period or the woman is under 50 years old, contraception should be used to avoid pregnancy. You should consult a doctor.

HRT and tumors

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

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The use of estrogen-only HRT increases the risk of excessive thickening of the uterine lining (endometrial hyperplasia) and uterine lining cancer (endometrial cancer). This additional risk is prevented by taking a medicine containing estrogen and a progestogen 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 (uterus removal), they should discuss with their doctor whether they can safely take this medicine without a progestogen.
Among women with a uterus who do not use HRT, endometrial cancer is diagnosed in an average of 5 out of 1000 women between the ages of 50 and 65.
Among women between the ages of 50 and 65 with a uterus who use estrogen-only 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 use 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 stopping therapy. Tumors diagnosed in women using estriol were less advanced clinically than in women not using estriol.
To reduce the risk of endometrial stimulation, the maximum daily dose should not be exceeded, and the maximum daily dose should not be used 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.

Bleeding or spotting may occur during the first few months of HRT.
However, if bleeding or spotting:

• lasts longer than the first few months,
• occurs after some time using HRT,
• continues even after stopping HRT, you should consult a doctor, who will decide whether these symptoms require further examination.

Breast cancer

Evidence confirms that the use of hormonal replacement therapy (HRT) in the form of combined estrogen-progestogen therapy or estrogen-only therapy increases the risk of breast cancer. This additional risk depends on the duration of HRT and 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 longer if HRT lasted more than 5 years.
Comparison
Breast cancer is diagnosed in an average of 13-17 out of 1000 women between the ages of 50 and 54 who do not use HRT.
In the case of 50-year-old women who start 5-year estrogen-only HRT, the number of cases will be 16-17 out of 1000 patients (i.e., 0-3 additional cases).
In the case of 50-year-old women 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 use HRT, breast cancer is diagnosed in an average of 27 out of 1000 women over a period of 10 years.
In the case of 50-year-old women who start 10-year estrogen-only HRT, the number of cases will be 34 out of 1000 patients (i.e., 7 additional cases).
In the case of 50-year-old women who start 10-year combined estrogen-progestogen HRT, the number of cases will be 48 out of 1000 patients (i.e., 21 additional cases).
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You should regularly examine your breasts and consult a doctor if you notice any changes, such as:

• indentation or retraction of the skin
• changes in the nipples
• any visible or palpable thickening and/or lumps.

It is not known whether the use of Ovestin is associated with the same increased risk of breast cancer as the use of other HRT medications. People concerned about the risk of breast cancer should discuss the benefits and risks of such therapy with their doctor.

Ovarian cancer

Ovarian cancer is rare - much rarer than breast cancer. The use of HRT containing 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 use HRT, ovarian cancer is diagnosed over a period of 5 years in approximately 2 out of 2000 women. In women who have taken HRT for 5 years, it occurs in approximately 3 out of 2000 women (i.e., approximately 1 additional case).
It is not known whether the use of Ovestin is associated with the same increased risk as the use of other HRT medications.

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 using HRT than in those not using HRT, especially in the first year of treatment.
Venous thrombosis can be severe. If a clot enters the lungs, it can cause chest pain, shortness of breath, fainting, or even death.
The likelihood of blood clots in veins increases with age and in the following situations. If any of the following situations apply to the patient, they should inform their 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/m)
• blood clotting disorders requiring long-term use of anticoagulant medications
• venous thrombosis in the legs, lungs, or other organs in a close relative
• systemic lupus erythematosus
• cancer.

Symptoms of venous thrombosis are listed in "Stop using Ovestin and consult a doctor immediately".
Comparison
In the population of women over 50 years old who do not use HRT, venous thrombosis can be expected to occur in 4-7 out of 1000 women over a period of 5 years. In women of the same age using combined estrogen-progestogen HRT, the number of cases will be 9-12 out of 1000 women over a period of 5 years (i.e., 5 additional cases).
In the group of women over 50 years old who have had a hysterectomy and used estrogen-only 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 the use of Ovestin is associated with the same increased risk as the use of other HRT medications.

Heart disease (heart attack)

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

Stroke

The risk of stroke is approximately 1.5 times higher in women using HRT than in those not using HRT. The number of additional stroke cases associated with HRT increases with age.
Comparison
It is estimated that in women over 50 years old who do not use HRT, stroke can be expected to occur over a period of 5 years in approximately 8 out of 1000 women, and in women of the same age using HRT, the number of cases will be 11 out of 1000 women over a period of 5 years (i.e., 3 additional cases).

Other disorders

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

Ovestin and other medications

Some medications may affect the efficacy of Ovestin, and Ovestin may affect the efficacy of other medications, which can lead to irregular bleeding. This applies to the following medications:

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

You should tell your doctor or pharmacist about all medications you are currently taking or have recently taken, as well as any medications you plan to take, including those that are available without a prescription, herbal products, and other natural products.

Lab tests

If blood tests are necessary, you should inform your doctor or laboratory staff that you are using Ovestin, as it may affect the results of some tests.

Ovestin with food and drink

Food and drink do not affect the efficacy of Ovestin therapy.

Pregnancy and breastfeeding

Ovestin is intended for use in postmenopausal women only. If you become pregnant, you should stop using Ovestin and consult a doctor.
Women who are breastfeeding should consult a doctor before using Ovestin.

Driving and using machines

The use of Ovestin should not affect your ability to drive or operate machines. However, individual reactions to the medicine may vary.
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Ovestin contains lactose monohydrate.

If you have been diagnosed with an intolerance to some sugars, you should consult a doctor before taking Ovestin.

3. How to use Ovestin

This medicine should always be used as directed by your doctor or pharmacist. If you are unsure, 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 between patients.
To improve wound healing in postmenopausal women undergoing vaginal surgery, 4-8 mg per day is usually used 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 used for 7 days in the week preceding the smear.
The score line on the tablet is only to facilitate breaking the tablet to make it easier to swallow.
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. Doses should not be divided.
Your doctor will try to prescribe the lowest possible dose that should be taken for the shortest time necessary to alleviate symptoms.
If you feel that the effect of Ovestin is too strong or too weak, you should consult a doctor.

Using a higher dose of Ovestin than recommended

If you have taken more than the recommended dose of Ovestin, you should consult a doctor or pharmacist immediately.
In the case of taking a higher dose of Ovestin than recommended, it does not pose a threat to health and life. However, you should 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

You should not take a double dose to make up for a missed dose.
If you miss a tablet, you should take it as soon as possible, provided that the interval between tablets does not exceed 12 hours. If the interval is longer than 12 hours, you should 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 using Ovestin. It may be necessary to stop using Ovestin about 4-6 weeks before surgery to reduce the risk of blood clots (see "Blood clots in veins").
You should ask your doctor when you can start using Ovestin again.
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If you have any further doubts about using this medicine, you should consult a doctor or pharmacist.

4. Possible side effects

Like all medicines, Ovestin can cause side effects, although not everybody gets them.
In women using HRT, the following diseases occur more frequently than in those not using HRT:

• breast cancer
• abnormal growth or tumors of the uterine lining (hyperplasia or endometrial cancer)
• ovarian cancer
• presence of blood clots in the veins of the legs or lungs (venous thromboembolism)
• heart disease
• stroke
• possible memory loss in case of starting HRT at an age over 65.

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

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

In most patients, these symptoms usually disappear after the first few weeks of treatment.
The following side effects have been reported in the use of other HRT medications:

• gallbladder inflammation
• various skin disorders
• skin discoloration, especially on the face or neck (chloasma)
• painful red lumps on the skin (erythema nodosum)
• rash with plate-like, red lesions or ulcers (erythema multiforme)

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products,
Jerozolimskie Avenue 181C,
02-222 Warsaw,
phone: 22 49-21-301,
fax: 22 49-21-309,
website: https://smz.ezdrowie.gov.pl
By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Ovestin

The medicine should be stored out of sight and reach of children.
Store in a temperature below 30°C. Store in the original packaging to protect from light and moisture.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

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 silica, magnesium stearate, potato starch, povidone, lactose monohydrate.

What Ovestin looks like and contents of the packaging

White, round, flat tablets with a beveled edge, scored. Each tablet has the marking DG above the score line and the number 8 below the score line. The packaging contains 30 tablets.
For more detailed information, you should contact the marketing authorization holder or parallel importer.

Marketing authorization holder in the Netherlands, the country of export:

Aspen Pharma Trading Limited, 3016 Lake Drive, Citywest Business Campus, Dublin 24, Ireland

Manufacturer:

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

Parallel importer:

Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź

Repackaged by:

Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Netherlands marketing authorization number: RVG 09970

Parallel import authorization number: 238/23

Date of leaflet approval: 19.10.2023

[Information about the trademark]
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