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, 0.5 mg, vaginal capsules

Estriol

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.
• 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 not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. 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 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 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 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 to:

• accelerate the healing of postoperative wounds in women who have undergone vaginal surgery,
• facilitate the 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 risks 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 ask about the patient's health and family medical history. The doctor 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 the patient currently has or has had breast canceror 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 there is a suspicion of such a tumor.
• If there is vaginal bleeding of unknown cause.
• If there is untreated endometrial hyperplasia(thickening of the lining of the uterus).
• If the patient currently has or has had blood clots in the blood vessels(venous thrombosis), such as deep vein thrombosis or pulmonary embolism.
• If the patient has blood clotting disorders(such as protein C or protein S deficiency or antithrombin deficiency).
• If the patient currently has or has recently had arterial thromboembolic diseases, such as myocardial infarction, stroke, or angina pectoris.
• If the patient currently has or has had liver disease, and liver function tests have not returned to normal.
• If the patient has a rare blood disorder called "porphyria", which is inherited through family members.

If any of the above medical 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 in the past, as they may recur or worsen during treatment with Ovestin. If this happens, the patient should visit the doctor 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 patient's mother, sister, or grandmother),
• hypertension,
• liver disorders, such as liver tumors,
• diabetes with or without vascular complications,
• gallstones,
• migraine or severe headaches,
• systemic lupus erythematosus (SLE); a chronic disease affecting connective tissue with skin lesions all over the body,
• 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 medicines such as ombitasvir/paritaprevir/ritonavir and dasabuvir, taken with or without ribavirin. Taking these medicines with some estrogen-containing medicines may increase liver function test results (increased ALT enzyme activity); the risk of this happening with Ovestin is currently unknown.
The doctor should be told if the patient notices any changes in their condition while using Ovestin.
Ovestin 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",
• jaundice (yellowing of the skin and eyes), which may be a sign of liver disease,
• a significant increase in blood pressure (which may cause 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,
• breathing difficulties. More information can be found 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 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 (cancer of the uterine lining).

The use of estrogen-only HRT in tablet form for a long time may increase the risk of developing endometrial cancer.
It is not certain whether a similar risk exists with the repeated or prolonged (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 a 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 (maximum 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 treatment with Ovestin, 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 should be performed and a doctor consulted if any changes are noticed, such as:

• indentation or retraction of the skin,
• changes in the nipple,
• any visible or palpable thickening and/or 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. 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 circulation

Blood clots in veins (venous thrombosis)

The risk of developing blood clots in veinsis 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 be severe. 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 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"),
• severe obesity (body mass index over 30 kg/m2),
• blood clotting disorders requiring long-term use of anticoagulant medications,
• venous thrombosis in the legs or lungs or other organs in close relatives,
• systemic lupus erythematosus (SLE); a chronic disease affecting connective tissue with skin lesions all over the body,
• 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, 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 years old who 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 (myocardial infarction)

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 increases with age.
Comparison
It is estimated that in women over 50 years old who do not use HRT, over a 5-year period, stroke can be expected to occur in about 8 out of 1000 women, and in women of the same age using HRT, the rate is 11 cases per 1000 women over 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. 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, including those that are not prescribed, herbal medicines, or other natural products.
Some medicines may affect the efficacy 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

If 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 efficacy of Ovestin treatment.

Pregnancy and breastfeeding

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

Driving and using machines

The use of Ovestin should not affect the 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 exactly as advised by the doctor or pharmacist. In case of doubt, consult a doctor or pharmacist.
In the case of atrophic changes in the lower genital tract, 1 capsule is usually used daily for the first weeks (maximum 4 weeks), then the dose is gradually reduced to 1 capsule twice a week.
To improve wound healing in postmenopausal women who have undergone vaginal surgery, 1 capsule is usually used daily for 2 weeks before surgery and 1 capsule twice a week for 2 weeks after surgery.
To facilitate the interpretation of cervical smear results in postmenopausal women, 1 capsule is usually used every other day in the week preceding the smear.
The capsule should be inserted deep into the vagina in a half-lying position before going to bed at night. The capsule should not be used rectally.
The doctor will try to prescribe the lowest dose that should be taken for the shortest time necessary to alleviate the symptoms. If the patient feels that the action of Ovestin is too strong or too weak, they should consult a doctor.

Using more than the recommended dose of Ovestin

In case of taking a higher dose than recommended, a doctor or pharmacist should be consulted immediately.
In case of swallowing the capsule, 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, 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 the missed dose is noticed on 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 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 (venous thrombosis)"). The doctor should be asked when it will be possible to start using Ovestin again.
In case of any further doubts about the use of this medicine, a doctor or pharmacist should be consulted.

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 medicines that enter the bloodstream, the following diseases were more frequently reported. The following risks are less likely to apply to vaginal medicines like Ovestin:

• ovarian cancer,
• blood clots in the veins of the legs or lungs (venous thromboembolic 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:

• breast tenderness and swelling,
• mild vaginal bleeding,
• increased vaginal discharge,
• nausea,
• fluid retention, 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.
The following side effects have been reported during the use of other HRT medications:

• cholecystitis (inflammation of the gallbladder),
• various skin disorders:
• changes in skin pigmentation, 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 not listed in this leaflet, the doctor, pharmacist, or nurse should be informed. Side effects can be reported directly to the Department of Adverse Reaction Monitoring 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.
Store in a temperature between 2°C and 25°C in the original packaging. Protect from light and moisture.
Do not use 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. A 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, 0.5 mg. The other ingredients are: Witepsol S 58.

What Ovestin looks like and contents of the packaging

White, oval capsules. Each blister contains 5 vaginal capsules. The blisters are in a cardboard box.
For more detailed information, the marketing authorization holder or parallel importer should be contacted.

Marketing authorization holder in Romania, the country of export:

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

Manufacturer:

N.V. Organon, Kloosterstraat 6, 5349 AB Oss, Netherlands
UNITHER INDUSTRIES, Zone Industrielle le Malcourlet, 03800 Gannat, France

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
Romanian marketing authorization number: 3386/2011/01

Parallel import authorization number: 210/19 Date of leaflet approval: 11.05.2022

[Information about the trademark]