Ovestin

Leaflet attached to the packaging: patient information

Warning! Keep the leaflet, information on the immediate packaging in a foreign language!

Ovestin(Physiogine)

0.5 mg, vaginal capsules

Estriol
Ovestin and Physiogine 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 you need to.
• If you have 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 or pharmacist. See section 4.

Table of contents of the leaflet:

• 1. What Ovestin is and what it is 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 Ovestin is and what it is used for

Ovestin belongs to a group of medicines called hormone replacement therapy (HRT) for vaginal use. The medicine contains the female sex hormone estriol (estrogen). Ovestin is used in women after menopause, at least 12 months after the end of natural menstruation.
Ovestin is used to relieve menopausal symptoms 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 inflammation 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 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, so the hormone is released where it is needed.
This can relieve discomfort in the vagina.
Improvement may only be noticeable after a few days or even weeks.
In addition to the above indications, Ovestin vaginal capsules may also be used for:

• accelerating the healing of post-operative wounds in women who have undergone vaginal surgery
• accurate assessment of cervical smears 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 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 HRT may vary. You should always consult a doctor.
Before starting (or resuming) HRT, the doctor will take a medical history and examine the patient's health and family medical history. 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 self-examinations as recommended by your doctor.

When not to use Ovestin:

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

• If the patient is allergicto estriol or any of the other ingredients of this medicine (listed in section 6 "Contents of the packaging and other information").
• If breast canceris present or has been diagnosed in the past, or if there is a suspicion of breast cancer.
• If there is an estrogen-dependent tumor, such as endometrial cancer (the lining of the uterus), or if such a tumor is suspected.
• If there is vaginal bleedingof unknown cause.
• If there is untreated endometrial hyperplasia(thickening of the lining of the uterus).
• If blood clots in blood vessels(thrombosis) have occurred or are occurring, such as deep vein thrombosis or pulmonary embolism.
• If there are blood clotting disorders(such as protein C or protein S deficiency, or antithrombin deficiency).
• If there are or have been arterial diseasescaused by blood clots, such as heart attack, stroke, or angina pectoris.
• If there is or has been liver disease, and liver function tests have not returned to normal.
• If the patient has a rare blood disease called "porphyria", which is inherited through family members.

If any of the above health conditions occur for the first time while using Ovestin, treatment should be stopped immediately and a doctor consulted.

Warnings and precautions

Before starting treatment, the doctor should be informed if any of the following conditions are present or have occurred, as they may return or worsen during Ovestin treatment. If this happens, the doctor should be consulted more frequently:

• uterine fibroids (uterine leiomyoma)
• endometriosis (growth of endometrial tissue outside the uterus) or a history of 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 liver tumors
• diabetes with or without vascular complications
• gallstones
• migraine or severe headaches
• systemic lupus erythematosus (SLE); chronic connective tissue disease with skin changes
• epilepsy
• asthma
• otosclerosis (a disease affecting the eardrum and causing hearing loss)
• fluid retention due to heart or kidney disease

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 increase liver enzyme levels (ALT); the risk of this occurring with Ovestin is currently unknown.
The doctor should be told if any changes in the patient's condition occur while using Ovestin.
Ovestin treatment should be stopped and a doctor consulted immediatelyif any of the following conditions occur during HRT:

• any of the conditions listed in "When not to use Ovestin"
• yellowing of the skin and eyes (jaundice), which may be a sign of liver disease
• significant increase in blood pressure (which may cause headaches, 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
• breathing difficulties

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. A doctor should be consulted.

HRT and tumors

Endometrial hyperplasia (thickening of the uterine lining) and endometrial cancer.

Long-term use of estrogen-only HRT in the form of tablets may increase the risk of endometrial cancer.
It is not certain whether this risk also applies to 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 should not usually be a cause for concern, but a doctor should be consulted. This may be a sign of endometrial hyperplasia.
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 following risks 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 following conditions will worsen or recur during Ovestin treatment, but if in doubt, a doctor should be consulted.

Breast cancer

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

Regular breast examinations and consultation with a doctor in case of any changes, such as:

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

In addition, it is recommended to undergo regular mammography screening as advised by the 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 aged 50-54 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.
Venous thrombosis can have a severe course. 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, 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 that require long-term use of anticoagulant medications
• venous thrombosis in the legs or lungs, or other organs, in close relatives
• systemic lupus erythematosus (SLE); chronic connective tissue disease with skin changes
• cancer.

Symptoms of venous thrombosis are listed in "When to stop using Ovestin and consult a doctor immediately".
Comparison
In the population of women over 50 who do not use HRT, on average, 4 to 7 out of 1000 women can expect to develop venous thrombosis over a 5-year period.
In the group of women over 50 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 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 increases with age.
Comparison
It is estimated that in women over 50 who do not use HRT, stroke will occur in about 8 out of 1000 women over a 5-year period, and in women of the same age using HRT, the rate will be 11 cases per 1000 women over a 5-year period (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. A doctor should be consulted in this regard.

Ovestin and other medicines

The doctor or pharmacist should be told about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including those that are available without a prescription, herbal medicines, or other natural products.
Some medicines may affect the effectiveness of Ovestin, and Ovestin may affect the action of other medicines. This may 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

When laboratory blood tests are necessary, the doctor or laboratory staff should be informed about the use of Ovestin, as it may affect the results of some tests.

Ovestin with food and drink

Food and drink do not affect the effectiveness of Ovestin treatment.

Pregnancy and breastfeeding

Ovestin is intended for use only in women after menopause. If pregnancy occurs, Ovestin treatment should be stopped and a doctor consulted.
Women who are breastfeeding should consult a doctor before using Ovestin.

Driving and operating machinery

The use of Ovestin should not affect the ability to drive or operate machinery. However, individual reactions to the medicine may vary.

3. How to use Ovestin

This medicine should always be used as directed by a doctor or pharmacist. If in doubt, consult a doctor or pharmacist.
In the case of atrophic changes in the lower genital tract, 1 vaginal capsule is usually used daily for the first weeks (up to 4 weeks), then the dose is gradually reduced to 1 vaginal capsule twice a week.
To improve wound healing in postmenopausal women who have undergone vaginal surgery, 1 vaginal capsule is usually used daily for 2 weeks before surgery and 1 vaginal capsule twice a week for 2 weeks after surgery.
To facilitate the interpretation of cervical smear results in postmenopausal women, 1 vaginal capsule is usually used every other day in the week preceding the smear.
The vaginal capsule should be inserted deeply into the vagina in a half-lying position before going to bed. The vaginal capsule should not be used rectally.
The doctor will try to prescribe the lowest possible dose that should be taken for the shortest time necessary to relieve symptoms.
If you feel that the effect of Ovestin is too strong or too weak, you should consult a doctor.

Using more than the recommended dose of Ovestin

In case of taking a higher dose of Ovestin than recommended, a doctor or pharmacist should be consulted immediately.
If a vaginal capsule is swallowed, it does not pose a risk to health and life. However, a doctor should be informed. 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

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

Need for surgery

Patients who are to undergo surgery should tell 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"). A doctor should be asked when it will be possible to start using Ovestin again.
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 in the form of medications that enter the bloodstream, the following diseases have been reported more frequently. The following risks are less likely to apply to vaginal medications like Ovestin:

• ovarian cancer
• blood clots in veins (venous thromboembolic disease)
• stroke
• possible memory loss if HRT is started at an age over 65

For more information on side effects, see 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, usually manifested 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.
The following side effects have been reported during the use of other HRT medications:

• cholecystitis (inflammation of the gallbladder)
• 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 patches or ulcers (erythema multiforme).

Reporting side effects

If any side effects occur, including any side effects not listed in this leaflet, a doctor or pharmacist should be told. 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 181 C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting side effects 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.
Store at a temperature below 25°C. Protect from light and moisture.
Do not use this medicine after the expiry date stated on the packaging.
The batch number and expiry date are embossed on the edges of the blister pack.
Medicines should not be disposed of via wastewater or household waste. A pharmacist should be asked 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, 0.5 mg.
The other ingredients are Witepsol S 58.

What Ovestin looks like and contents of the pack

White, oval vaginal capsules. The packaging contains 15 vaginal capsules. PVC/PE blisters are located in a cardboard box.
For more detailed information, the marketing authorization holder or parallel importer should be consulted.

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:

Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź

Repackaged by:

Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Laboratorium Galenowe Olsztyn Sp. z o.o.
ul. Spółdzielcza 25A
11-001 Dywity
Pharma Innovations Sp. z o.o.
ul. Jagiellońska 76
03-301 Warszawa
CEFEA Sp. z o.o. Sp. komandytowa
ul. Działkowa 56
02-234 Warszawa
IVA Pharm Sp. z o.o.
ul. Drawska 14/1
02-202 Warszawa
CANPOLAND SPÓŁKA AKCYJNA
ul. Beskidzka 190
91-610 Łódź
Marketing authorization number in France, the country of export: 34009 329 690 0 5
329 690-0
Parallel import authorization number: 228/18
Date of leaflet approval: 08.05.2023
[Information about the trademark]