Ovestin

Leaflet accompanying the packaging: information for the user

Warning! Keep the leaflet! Information on the immediate packaging in a foreign language.

Ovestin (Physiogine)

0.5 mg, vaginal globules

Estriol
Ovestin and Physiogine are different trade names for the same medicine.

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 administration. 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 symptoms of menopause that occur 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 can lead to painful intercourse and the occurrence of inflammatory conditions and intense itching of the vagina. Estrogen deficiency can also cause symptoms of urinary incontinence and recurrent urinary tract infections. These symptoms often disappear after the use of 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, and 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

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 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 or pharmacist. See section 4.
• for the accurate assessment of a cervical smear in postmenopausal women.

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 hormone replacement 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 vary. You should always consult a doctor. Before starting (or resuming) HRT, the doctor will take a medical history and ask about the patient's health and any diseases that occur in the family. They may also decide to perform a physical examination, including a breast examination and/or a 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 with your doctor the benefits and risks associated with continuing to use Ovestin. 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. In case of uncertainty, before using Ovestin, you should consult a doctor. When not to use Ovestin:

If any of the above conditions occur for the first time during the use of Ovestin, you should stop using it immediately and consult a doctor.

Warnings and precautions

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

• 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 developing an estrogen-dependent tumor (such as breast cancer in the mother, sister, or grandmother).
• high blood pressure
• liver disorders, such as a benign liver tumor
• diabetes with or without vascular complications
• gallstones
• migraine or severe headaches
• an immune system disease affecting multiple organs (systemic lupus erythematosus - SLE; chronic connective tissue disease with skin changes throughout the body)
• epilepsy
• asthma
• a disease affecting the eardrum and causing hearing loss (otosclerosis)
• fluid retention in the body due to heart or kidney disease
• hereditary and acquired angioedema.

You should inform your doctor if the patient has hepatitis C and is being treated with medications such as ombitasvir/paritaprevir/ritonavir and dasabuvir, given with ribavirin or without. Taking these medications with some estrogen-containing medications may cause elevated liver function test results (increased liver enzyme ALT activity); the risk of this occurring with Ovestin is currently unknown. You should tell your doctor if you notice any changes in your condition while using Ovestin. You should stop using Ovestin and consult a doctor immediatelyif you experience any of the following symptoms during 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
• 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 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)".

Warning: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, it may be necessary to use an additional method of contraception. You should consult a doctor.

HRT and tumors

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

The use of estrogen-only HRT in the form of tablets for a long time may increase the risk of developing uterine lining cancer (endometrium). There is no certainty whether a similar risk exists in the case of 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, the addition of progestogen is not necessary. Bleeding or spotting is not usually a cause for concern, but you should consult a doctor. It may be a sign of endometrial thickening. To prevent endometrial stimulation, you should not exceed the maximum dose or take it for longer than a few weeks (up to 4 weeks). The risks described below are related to HRT medications that enter the bloodstream. Ovestin, on the other hand, 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 during the use of Ovestin, but if you have any doubts, you should consult a doctor.

Breast cancer

Data indicate that the use of 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.

You should regularly examine your breasts and consult a doctor if you notice any changes, such as:

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

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

Ovarian cancer

Ovarian cancer is rare - much rarer than breast cancer. The use of 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 the ages of 50 and 54 who do not use HRT, ovarian cancer will be diagnosed in about 2 out of 2000 women over a period of 5 years. 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 developing blood clots in the veins is about 1.3 to 3 times higher in women using HRT than in those who do not use HRT, especially in the first year of treatment. The development 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 developing blood clots in the veins increases with age and in the following situations. If any of the following situations apply to you, you should 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/m)
• blood clotting disorders that require long-term use of anticoagulant medications
• venous thrombosis in the legs, lungs, or other organs in a close relative
• systemic lupus erythematosus (SLE; 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". ComparisonIn women over 50 years old who do not use HRT, on average, 4 to 7 out of 1000 women can expect to develop venous thrombosis over a period of 5 years. 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 who do not use HRT. The number of additional cases of stroke associated with HRT increases with age. ComparisonIn women over 50 years old who do not use HRT, on average, 8 out of 1000 women can expect to develop stroke over a period of 5 years, and in women of the same age using HRT, the rate is 11 cases per 1000 women over a period of 5 years (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 a doctor about this.

Ovestin and other medicines

You should 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 that are available without a prescription, herbal medicines, or other natural products. Some medicines may affect the action of Ovestin, which can lead to irregular bleeding. This applies to the following medicines:

• antiepileptic drugs(such as phenobarbital, phenytoin, and carbamazepine)
• medicines used to treat tuberculosis(such as rifampicin, rifabutin)
• medicines used to treat HIV infection(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, 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 treatment with Ovestin.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should consult a doctor or pharmacist before using this medicine. Ovestin is intended for use only in postmenopausal women. 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.

3. How to use Ovestin

This medicine should always be used as directed by your doctor or pharmacist. If you are unsure, you should consult a doctor or pharmacist. In the case of atrophic changes in the lower urinary and genital tract, 1 globule is usually used per day for the first few weeks (up to 4 weeks), then the dose is gradually reduced to 1 globule twice a week. To improve wound healing in postmenopausal women who have undergone vaginal surgery, 1 globule is usually used per day for 2 weeks before surgery and 1 globule twice a week for 2 weeks after surgery. To facilitate the interpretation of cervical smear results in postmenopausal women, 1 globule is usually used every other day in the week preceding the smear. The globule should be inserted deep into the vagina in a half-lying position before going to bed at night. The globule should not be used rectally. Your doctor will try to prescribe the lowest possible dose that should be taken for the shortest time necessary to alleviate the 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. If you have swallowed a globule, it does not pose a risk to your health and life. However, you should inform your doctor about it. 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 dose, you should take it as soon as possible, unless you are due to take the next globule on the same day. If you miss a dose and it is the day you are due to take the next globule, you should skip the missed dose and continue with 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 to 6 weeks before surgery to reduce the risk of blood clots (see section 2 "Blood clots in veins"). You should ask your doctor when you can start using Ovestin again. If you have any further doubts about the use of 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. The following diseases are more frequently reported in women using HRT in the form of medications that enter the bloodstream than in women who do not use HRT. These risks apply to a lesser extent to medications used vaginally, such as Ovestin:

• ovarian cancer
• blood clots in the veins of the legs or lungs (venous thromboembolism)
• 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:

• 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
• local irritation or itching
• flu-like symptoms.

Most patients experience these symptoms during the first few weeks of treatment and they usually disappear on their own. 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 lumps on the skin (erythema nodosum)
• a rash with round redness 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 or pharmacist. Side effects can be reported directly to the Department of Drug Safety, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. By reporting side effects, you can help gather more information on the safety of the medicine.

5. How to store Ovestin

The medicine should be stored out of sight and reach of children. Do not store above 25°C. Protect from light and moisture. Do not use Ovestin after the expiry date stated on the packaging. The expiry date refers to the last day of the specified 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. Each globule contains 0.5 mg of estriol. The other ingredients are: solid fat (contains macrogol ester of stearic acid and glycerol ricinoleate).

What Ovestin looks like and what the packaging contains

White, oval globules. Each blister contains 5 vaginal globules. The blisters are in a cardboard box. The packaging contains 15 globules. For more detailed information, you should contact the marketing authorization holder or parallel importer.

Marketing authorization holder in France, the country of export:

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

Manufacturer:

Unither Industries Zone Industrielle le Malcourlet, 03800 Gannat, France

Parallel importer:

InPharm Sp. z o.o. ul. Strumykowa 28/11 03-138 Warsaw

Repackaged by:

InPharm Sp. z o.o. Services sp. k. ul. Chełmżyńska 249 04-458 Warsaw Marketing authorization number in France, the country of export:3400932969005 3296900 Parallel import authorization number:24/10

Date of leaflet approval: 30.01.2025

[Information about the trademark]