Ovestin

Leaflet attached to the packaging: information for the user

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

Ovestin, 1 mg/g, vaginal cream

Estriol

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

• •This leaflet should be kept so that it can be read again if necessary.
• In case of any doubts, the doctor or pharmacist should be consulted.
• This medicine has been prescribed to a specific person. It should not be given to others. The medicine may harm another person, even if the symptoms of their illness 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 belongs to a group of medicines known as hormone replacement therapy (HRT) for vaginal use. The medicine contains the female sex hormone estriol (estrogen). Ovestin is used in postmenopausal women, at least 12 months after the last natural menstrual period. Ovestin is used to alleviate menopausal symptoms in the vagina, such as dryness or irritation. In medical terminology, this phenomenon is referred to as "atrophic vaginitis". It is caused by a decrease in estrogen levels in the body and occurs naturally after menopause. If the ovaries are surgically removed before menopause (a procedure called oophorectomy), estrogen production decreases very quickly. 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. These symptoms often disappear after using estrogen-containing medications. Noticeable improvement usually occurs after a few days or weeks of treatment. Ovestin works by replacing estrogen, which is normally produced by the woman's ovaries. The medicine is administered vaginally, so the hormone is released where it is needed. This can alleviate the feeling of discomfort in the vagina. Improvement may only be noticeable after a few days or even weeks. In addition to the above indications, Ovestin may also be used for:

• accelerating the healing of postoperative wounds in women undergoing vaginal surgery
• accurate assessment of cervical smears in postmenopausal women.

2. Important information before using Ovestin

Medical history and regular check-ups

Using 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 be varied. The doctor should always be consulted. Before starting (or resuming) HRT, the doctor will take a medical history and may decide to perform a physical examination, including a breast and/or gynecological examination. After starting Ovestin, regular check-ups with the doctor should be scheduled (at least once a year). During the check-up, the benefits and risks associated with continuing Ovestin should be discussed with the doctor. Regular breast exams should be performed as recommended by the doctor.

When not to use Ovestin

Ovestin should not be used if any of the following situations apply to the patient. In case of uncertainty, the doctor should be consulted before using Ovestin. When not to use Ovestin:

• if the patient is allergic to estriol or any of the other ingredients of this medicine (listed in section 6 "Contents of the packaging and other information").
• if the patient has or has had breast cancer or if there is a suspicion of breast cancer.
• if the patient has or has had an estrogen-dependent tumor, such as endometrial cancer (cancer of the uterine lining), or if there is a suspicion of such a tumor.
• if the patient has vaginal bleeding of unknown cause.
• if the patient has untreated excessive thickening of the uterine lining (endometrial hyperplasia).
• if the patient has or has had blood clots in the blood vessels (venous thrombosis), such as in the deep veins of the legs (deep vein thrombosis) or in the pulmonary vessels (pulmonary embolism).
• if the patient has blood clotting disorders (such as protein C deficiency, protein S deficiency, or antithrombin deficiency).
• if the patient currently has or has recently had diseases caused by the presence of blood clots in the arteries, such as heart attack, stroke, or angina pectoris.
• if the patient has or has had liver disease, and liver function tests have not returned to normal.
• if the patient has a rare blood disease called porphyria, which is inherited by family members.

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

Warnings and precautions

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 return or worsen during Ovestin use. If this happens, the doctor should be consulted more frequently:

• uterine fibroids (smooth muscle tumor)
• 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 developing an estrogen-dependent tumor (e.g., breast cancer in the mother, sister, or grandmother)
• high blood pressure
• liver disorders, such as a benign liver tumor
• diabetes with or without vascular changes
• gallstones
• migraine or severe headache
• immune system disease affecting multiple internal organs (systemic lupus erythematosus; chronic connective tissue disease with skin changes 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
• hereditary and acquired angioedema.

The doctor should be informed if the patient has hepatitis C and is being treated with medications such as ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin. Taking these medications with some estrogen-containing medications may cause elevated liver function test results (increased ALT enzyme activity); the risk of this occurring with Ovestin is currently unknown. The doctor should be told if any changes in the patient's condition are noticed while using Ovestin. Ovestin use should be stopped and the doctor consulted immediatelyif any of the following symptoms occur during HRT use:

• 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
• swelling of the face, tongue, and/or throat, and/or difficulty swallowing or hives, along with difficulty breathing, suggesting angioedema.
• significant increase in blood pressure (possible symptoms include headache, fatigue, dizziness)
• migraine-like headaches that occur for the first time
• pregnancy
• symptoms 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 the last menstrual period or the patient is under 50 years old, an additional method of contraception may be necessary. The doctor should be consulted.

HRT and tumors

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

Using estrogen-only HRT in tablet form for a long time may increase the risk of developing uterine lining cancer (endometrium). There is no certainty whether a similar risk exists with repeated or long-term (longer than one year) use of Ovestin. However, it has been shown that Ovestin is absorbed into the bloodstream to a very small extent, and therefore, adding a progestogen is not necessary. Bleeding or spotting is not usually a cause for concern, but the doctor should be consulted. This may be a sign of endometrial thickening. To prevent endometrial stimulation, the maximum dose should not be exceeded, and it should not be taken for longer than a few weeks (up to 4 weeks). The risks described below are associated with HRT medications that enter the bloodstream. However, Ovestin is used locally in the vagina and is absorbed into the bloodstream in very small amounts. It is less likely that the conditions listed below will worsen or recur while using Ovestin, but if there are any doubts, the doctor should be consulted.

Breast cancer

Data indicate that using Ovestin does not increase the risk of breast cancer in women who have never had it before. It is not known whether Ovestin can be safely used in women who have had breast cancer.

The following changes should be reported to the doctor:

• indentation of the skin
• changes in the nipples
• any visible or palpable lumps.

In addition, it is recommended to perform screening mammograms as advised by the doctor.

Ovarian cancer

Ovarian cancer is rare – much rarer than breast cancer. Using estrogen-only HRT is associated with a slightly increased risk of ovarian cancer. The risk of ovarian cancer depends on age. For example, in women between 50 and 54 years old who do not use HRT, ovarian cancer will be diagnosed in about 2 out of 2000 women over a 5-year period. In women who use HRT for 5 years, ovarian cancer will be diagnosed in about 3 out of 2000 women (i.e., about 1 additional case).

Effect of HRT on the heart or circulatory system

Blood clots in veins (venous thrombosis)

The risk of blood clots in veins is about 1.3 to 3 times higher in women using HRT than in those not using HRT, especially in the first year of treatment. The formation of blood clots can have serious consequences, and if a clot reaches 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 these situations apply to the patient, the doctor should be informed:

• 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 requiring long-term use of anticoagulant medications
• venous thrombosis in the legs, lungs, or other organs in a close relative
• systemic lupus erythematosus (chronic connective tissue disease with skin changes throughout the body)
• cancer.

Symptoms of venous thrombosis are listed in "When to stop using Ovestin and consult a doctor immediately". The comparison: in women over 50 years old who do not use HRT, venous thrombosis is expected to occur in about 4 to 7 out of 1000 women over a 5-year period. In women over 50 years old who have used estrogen-only HRT for more than 5 years, the number of cases will be 5 to 8 out of 1000 women (i.e., 1 additional case).

Heart disease (heart attack)

In women using estrogen-only HRT, the risk of developing heart disease is not increased.

Stroke

The risk of stroke is about 1.5 times higher in women using HRT than in those not using HRT. The number of additional stroke cases associated with HRT use increases with age. The comparison: in women over 50 years old who do not use HRT, stroke is expected to occur in about 8 out of 1000 women over a 5-year period, while in women of the same age using 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. The doctor should be consulted about this.

Ovestin and other medications

The doctor or pharmacist should be told about all medications the patient is currently taking or has recently taken, including those that are available without a prescription, herbal remedies, or other natural products. Some medications may affect the action of Ovestin, which can lead to irregular bleeding. These include:

• antiepileptic medications(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)

Laboratory tests

If there is a need to perform blood tests, the doctor or laboratory staff should be informed about Ovestin use, as it may affect the results of some tests.

Ovestin with food and drink

Food and drink do not affect the action of Ovestin.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before using this medicine. Ovestin is intended for use in postmenopausal women only. If pregnancy occurs, Ovestin use should be stopped, and the doctor should be consulted. Breastfeeding women should consult their doctor before using Ovestin.

Driving and using machines

Using Ovestin is unlikely to affect the ability to drive or use machines. However, individual reactions to the medication may vary.

Ovestin contains cetyl alcohol and stearyl alcohol.

The medicine may cause local skin reactions (e.g., contact dermatitis).

3. How to use Ovestin

This medicine should always be used as directed by the doctor or pharmacist. In case of doubts, the doctor or pharmacist should be consulted. For atrophic changes in the lower urinary and genital tracts, the recommended dose is 1 application per day for the first weeks (up to 4 weeks), then the dose is gradually reduced to 1 application twice a week. To improve wound healing in postmenopausal women who have undergone vaginal surgery, the recommended dose is 1 application per day for 2 weeks before surgery and 1 application twice a week for 2 weeks after surgery. To facilitate the interpretation of cervical smear results in postmenopausal women, the recommended dose is 1 application every other day in the week preceding the smear. Ovestin cream should be used vaginally with an applicator, preferably before bedtime. 1 application (applicator filled to the circular mark) contains 0.5 g of cream, which corresponds to 0.5 mg of estriol.

• 1. Remove the cap from the tube, turn it upside down, and open the tube with the sharp end.
• 2. Screw the applicator onto the tube. Make sure the plunger is fully inserted into the applicator.

• 3. Slowly squeeze the cream into the applicator until the plunger stops at the point marked with a red ring (indicated by the arrows in the figure below).

• 4. Unscrew the applicator from the tube and put the cap back on the tube.
• 5. In a lying position, insert the applicator tip with the cream deeply into the vagina.

• 6. Slowly push the entire contents of the cream into the vagina using the plunger.

• 7. After use, the plunger should be removed from the applicator by overcoming the resistance point and both parts should be washed thoroughly with warm water and soap. Do not use detergents. After washing, both parts should be rinsed well. DO NOT PUT THE APPLICATOR IN HOT OR BOILING WATER.
• 8. The device can be reassembled by inserting the plunger into the applicator, overcoming the resistance point.

After the tube is empty, the applicator should be discarded. The attending doctor will try to prescribe the lowest possible dose, which should be taken for the shortest time necessary to alleviate the symptoms. If the effect of Ovestin is thought to be too strong or too weak, the doctor should be consulted.

Using a higher dose of Ovestin than recommended

In case of using a higher dose of Ovestin than recommended, the doctor or pharmacist should be consulted immediately. If the cream is swallowed, it does not pose a risk to health and life. However, the doctor should be informed. Symptoms of overdose are usually nausea and vomiting. In women, menstrual bleeding may also occur a few days later.

Missing a dose of Ovestin

A double dose should not be used to make up for a missed dose. If a dose is missed, the medicine should be used as soon as possible, unless it is the day of the next application. If the missed dose is noticed on the day of the next application, the missed dose should be skipped, and the next doses should be used according to the previously established schedule.

Need for surgery

Patients who are to undergo surgery should tell the surgeon that they are using Ovestin. It may be necessary to stop using Ovestin about 4 to 6 weeks before surgery to reduce the risk of blood clots (see section 2 "Blood clots in veins"). The doctor should be asked when it is possible to start using Ovestin again. If there are any further doubts about using this medicine, the doctor or pharmacist should be consulted.

4. Possible side effects

Like all medicines, Ovestin can cause side effects, although not everybody gets them. The following diseases are more frequently reported in women using HRT medications that enter the bloodstream than in those not using HRT. These risks apply to a lesser extent to vaginally administered medications like Ovestin:

• ovarian cancer
• blood clots in the veins of the legs or lungs (venous thromboembolism)
• stroke
• possible memory loss, if HRT use starts 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:

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

In most patients, these symptoms will disappear after a few weeks of treatment. During the use of other HRT medications, the following side effects have been reported:

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

Reporting side effects

If any side effects occur, including any side effects not listed in this leaflet, the doctor, pharmacist, or nurse should be informed. Side effects can be reported directly to the Department of Drug Safety Monitoring of the 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. 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. It should not be stored at temperatures above 25°C. It should not be frozen. The medicine should not be used after the expiration date stated on the packaging. The expiration date refers to the last day of the specified month. Medicines should not be disposed of in wastewater or household waste. The pharmacist should be asked how to dispose of unused medicines. 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 gram of cream contains 1 mg of estriol. The other ingredients are cetyl alcohol, stearyl alcohol, octyldodecanol, cetyl palmitate, glycerol, polysorbate 60, sorbitan stearate, lactic acid, chlorhexidine dihydrochloride, sodium hydroxide, and purified water.

What Ovestin looks like and what the packaging contains

Ovestin is a white to almost white, homogeneous, smooth cream with a characteristic, mild odor. It is supplied in an aluminum tube with a polyethylene cap and an applicator with a styrene-acrylonitrile cylinder and a polyethylene plunger, in a cardboard box. The packaging size is 15 g of cream in a tube. For more detailed information, the marketing authorization holder or parallel importer should be contacted.

Marketing authorization holder in Austria, the country of export:

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

Manufacturer:

Aspen Bad Oldesloe GmbH, Industriestrasse 32-36, D-23843 Bad Oldesloe, Germany

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
Austrian export license number: 17453

Parallel import license number: 38/25

Date of leaflet approval: 28.01.2025

[Information about the trademark]