OVESTIN

Package leaflet: Information for the user

Warning! Keep the leaflet. Information on the immediate packaging in a foreign language.
Ovestin, 0.5 mg, globules
Estriol
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

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 package 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. Ovestin contains the female sex hormone estriol (an estrogen). Ovestin is used in postmenopausal women, at least 12 months after the natural cessation of menstruation.

Ovestin is used to relieve menopausal symptoms in the vagina, such as dryness or irritation. In medical terminology, this condition is known as "atrophic vaginitis." It is caused by decreased estrogen levels in the body and occurs naturally after menopause.

If the ovaries have been surgically removed before menopause (a procedure called oophorectomy), estrogen production decreases rapidly.

Estrogen deficiency may cause dryness and increased sensitivity of the vaginal walls, leading to painful sexual intercourse and the occurrence of inflammatory conditions and intense vaginal itching. Estrogen deficiency may also cause urinary incontinence and recurrent urinary bladder infections. These complaints often improve after treatment with estrogen-containing medicines. Noticeable improvement usually occurs within a few days or weeks after starting treatment.

Ovestin works by replacing the estrogen normally produced by a woman's ovaries. The medicine is administered vaginally, so the hormone is released exactly where it is needed. This may help relieve vaginal discomfort.

Improvement may become noticeable after several days or even weeks.

In addition to the indications described above, Ovestin globules may also be used:

• to accelerate healing of wounds after vaginal surgery,
• to enable accurate assessment of cervical smears in postmenopausal women.

2. Information before using Ovestin

Medical history and regular check-ups
Hormone replacement therapy (HRT) carries risks that should be considered when deciding whether to start or continue treatment.
Experience with treating women who experience premature menopause (due to ovarian failure or surgical intervention) is limited. In women with premature menopause, the risks associated with HRT may differ. Always consult a doctor.
Before starting (or resuming) HRT, the doctor will take a detailed medical history, including family medical conditions. The doctor may also decide to perform a physical examination, including, if necessary, a breast examination and/or a vaginal gynecological examination.
After starting treatment with Ovestin, regular check-ups with your doctor are required (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing Ovestin therapy.
Regular breast examinations should be performed as recommended by your doctor.

When not to use Ovestin:
Do not use Ovestin if any of the following conditions apply to you. If in doubt, consult your doctor before using Ovestin.

• If you are allergic to estriol or any of the other ingredients of this medicine (listed in section 6, "Contents in the pack and other information").
• If you currently have or have previously had breast cancer, or if breast cancer is suspected.
• If you have an estrogen-dependent tumour, for example endometrial cancer (lining of the uterus), or if such a tumour is suspected.
• If you have vaginal bleeding of unknown cause.
• If you have untreated excessive thickening of the uterine lining (endometrial hyperplasia).
• If you currently have or have previously had blood clots in blood vessels (venous thromboembolism), for example in the deep veins of the legs (deep vein thrombosis) or in the lungs (pulmonary embolism).
• If you have blood clotting disorders (such as protein C deficiency, protein S deficiency, or antithrombin deficiency).
• If you currently have or have recently had arterial diseases caused by blood clots, such as myocardial infarction, stroke, or angina pectoris.
• If you currently have or have previously had liver disease, and liver function tests have not returned to normal.
• If you have the rare inherited blood disorder called "porphyria".

If any of the above medical conditions occur for the first time during treatment with Ovestin, stop treatment immediately and contact your doctor without delay.

Warnings and precautions
Before starting treatment, inform your doctor if any of the following conditions currently exist or have occurred previously, as these symptoms may recur or worsen during treatment with Ovestin. If this happens, more frequent check-ups with your doctor may be necessary:

• Uterine fibroids (leiomyoma),
• Growth of endometrial tissue outside the uterus (endometriosis), or previous excessive growth of the uterine lining (endometrial hyperplasia),
• Increased risk of blood clots (see section "Venous thromboembolism"),
• Increased risk of developing estrogen-dependent tumours (e.g. breast cancer in mother, sister, or grandmother),
• Hypertension,
• Liver disorders, such as benign liver tumours,
• Diabetes, with or without vascular complications,
• Gallstones,
• Migraine or severe headaches,
• Systemic autoimmune disease affecting multiple internal organs (systemic lupus erythematosus - SLE; chronic connective tissue disease with skin lesions throughout the body),
• Epilepsy,
• Asthma,
• Otosclerosis (a disease affecting the ear ossicles and causing hearing loss),
• Fluid retention associated with heart or kidney disease.

Inform your doctor if you have hepatitis C and are being treated with medications such as ombitasvir/paritaprevir/ritonavir with or without dasabuvir. Concurrent use of these drugs with certain estrogen-containing medicines may increase liver function test results (elevated liver enzyme ALT activity); the risk of this occurring with Ovestin is currently unknown.
Inform your doctor if you notice any changes in your condition while using Ovestin.

Stop using Ovestin and contact your doctor immediately if any of the following occur during HRT:

• Any of the conditions listed under "When not to use Ovestin",
• Yellowing of the skin or whites of the eyes (jaundice), which may indicate liver disease,
• Significant increase in blood pressure (which may present as headache, fatigue, dizziness),
• New-onset migraine-type headaches,
• Pregnancy,
• Symptoms suggesting blood clot formation, such as:
  • Painful swelling and redness in the legs,
  • Sudden chest pain,
  • Breathing difficulties. Further information is provided in the section "Venous thromboembolism (blood clots in blood vessels)".

Note: Ovestin is not a contraceptive. If less than 12 months have passed since your last menstrual period or if you are under 50 years of age, contraception should be used to prevent pregnancy. Consult your doctor.

HRT and tumours
Excessive thickening of the uterine lining (endometrial hyperplasia) and cancer of the uterine lining (endometrial cancer)
Long-term use of estrogen-only HRT in tablet form may increase the risk of developing cancer of the uterine lining (endometrium).
It is not certain whether a similar risk exists with repeated or long-term (longer than one year) use of Ovestin. However, Ovestin is known to be absorbed into the bloodstream only to a very small extent, and therefore the addition of a progestogen is not necessary.
Bleeding or spotting is usually not a cause for concern, but you should contact your doctor, as it may be a sign of endometrial thickening.
To prevent endometrial stimulation, do not exceed the maximum dose or use it for longer than a few weeks (maximum 4 weeks).

The following risks apply to systemic hormone replacement therapies (HRT) that enter the bloodstream. However, Ovestin is administered locally via the vaginal route and is absorbed into the bloodstream in very small amounts. It is less likely that the conditions listed below will worsen or recur during Ovestin treatment, but if in doubt, consult your doctor.

Breast cancer
Data indicate that Ovestin does not increase the risk of breast cancer in women who have never previously had the disease. It is unknown whether Ovestin can be safely used in women who have had breast cancer.
Regularly examine your breasts and consult your doctor if you notice any changes, such as:

• Dimpling or retraction of the skin,
• Changes in the nipple,
• Any visible or palpable lumps or thickening.

Additionally, screening mammography is recommended as advised by your doctor.

Ovarian cancer
Ovarian cancer is rare – significantly rarer than breast cancer. Estrogen-only HRT is associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer increases with age. For example, among women aged 50 to 54 who do not use HRT, ovarian cancer will be diagnosed in about 2 out of 2000 women over a 5-year period. Among 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).

Effects of HRT on the heart and circulatory system
Venous thromboembolism (blood clots in veins)
The risk of blood clots in veins is approximately 1.3 to 3 times higher in women using HRT than in those not using HRT, especially during the first year of treatment.
Venous thromboembolism can be serious. If a clot travels to the lungs, it may cause chest pain, shortness of breath, fainting, or even death.
The likelihood of developing venous blood clots increases with age and in the following situations. Inform your doctor if any of these apply to you:

• Prolonged immobilization due to major surgery, injury, or illness (see also section 3, "Need for surgery"),
• Significant overweight (body mass index above 30 kg/m²),
• Blood clotting disorders requiring long-term anticoagulant therapy,
• History of venous thrombosis in legs, lungs, or other organs in a close relative,
• Systemic lupus erythematosus (SLE),
• Cancer.

Symptoms of thrombosis are listed under "Stop using Ovestin and contact your doctor immediately".

Comparison
In women over 50 years of age not using HRT, approximately 4 to 7 out of 1000 women can be expected to develop venous thrombosis over a 5-year period.
Among women over 50 using estrogen-only HRT for more than 5 years, the number of cases increases to 5 to 8 per 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 approximately 1.5 times higher in women using HRT than in those not using it. The number of additional stroke cases associated with HRT use increases with age.

Comparison
It is estimated that among women over 50 not using HRT, stroke will 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 per 1000 women over 5 years (i.e. 3 additional cases).

Other disorders
HRT does not prevent memory loss. Some evidence suggests a higher risk of memory loss in women who start HRT after the age of 65. Consult your doctor regarding this issue.

Ovestin and other medicines
Inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those obtained without a prescription, herbal remedies, 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. The following medicines are involved:

• Antiepileptic drugs (such as phenobarbital, phenytoin, and carbamazepine),
• Medicines used to treat tuberculosis (such as rifampicin, rifabutin),
• Medicines used in HIV infection (such as nevirapine, efavirenz, ritonavir, and nelfinavir),
• Herbal products containing St. John's wort (Hypericum perforatum).

Laboratory tests
If blood tests are required, inform your doctor or laboratory staff that you are using Ovestin, as it may affect the results of certain 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 in postmenopausal women only. If pregnancy occurs, stop using Ovestin and contact your doctor.
Women who are breastfeeding should consult their doctor before using Ovestin.

Driving and operating machinery
Ovestin is not expected to affect the ability to drive or operate machinery. However, individual responses to the medicine may vary.

3. How to use Ovestin

This medicine should always be used exactly as directed by your doctor or pharmacist. In case of doubt,
you should consult your doctor or pharmacist.
For atrophic changes in the lower urinary and genital tract, 1 suppository is usually used once daily for the first
weeks (for up to 4 weeks maximum), then the dose is gradually reduced to 1 suppository twice a week.
To improve wound healing in postmenopausal women undergoing vaginal procedures, 1 suppository is
usually used once daily for 2 weeks before the procedure and 1 suppository twice weekly for 2 weeks after the
procedure.
To facilitate interpretation of cervical smear results in postmenopausal women, 1 suppository is usually used
every other day during the week preceding the smear collection.
The suppository should be inserted deep into the vagina while lying in a semi-reclining position, before going
to bed at night. Suppositories must not be used rectally.
Your doctor will try to prescribe the lowest possible dose, which should be used for the shortest duration
necessary to relieve your symptoms. If you feel that the effect of Ovestin is too strong or too weak, you should
consult your doctor.
Use of a higher than recommended dose of Ovestin
If you have used more than the recommended dose of this medicine, you should contact your doctor or
pharmacist immediately.
Ingestion of the suppositories does not pose a health or life hazard. However, you should inform your doctor.
Symptoms of overdose most commonly include nausea and vomiting; in women, vaginal bleeding may also occur
after a few days.
Missed dose of Ovestin
Do not use a double dose to make up for a missed dose.
If you have missed a dose, take it as soon as possible, unless you notice the omission on the day the next dose
is due. If the missed dose is noticed on the day of the next scheduled dose, skip the missed dose and continue
with the next dose according to your regular schedule.
Surgery
Patients scheduled for surgery should inform the surgeon that they are using Ovestin. It may be necessary to
discontinue Ovestin approximately 4 to 6 weeks before surgery to reduce the risk of blood clots (see section 2
"Blood clots in veins (venous thrombosis)"). Please ask your doctor when you may resume using Ovestin.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like any medicine, this medicine may cause adverse effects, although not everyone experiences them.
The following conditions have been more frequently reported in women using systemic HRT (hormone replacement therapy) administered in forms that enter the bloodstream. The risks listed below are less relevant for locally administered vaginal products such as Ovestin:

• ovarian cancer,
• presence of blood clots in the veins of the legs or lungs (venous thromboembolic disease),
• stroke,
• possible memory loss if HRT is initiated after the age of 65.

For more information on adverse effects, see section 2.
Depending on the doses used and individual patient sensitivity, the following adverse effects may occur:

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

In most patients, these symptoms resolve after the first few weeks of treatment.
The following adverse effects have been reported with the use of other medicines in hormone replacement therapy:

• inflammation of the gallbladder,
• various skin disorders:
• skin pigmentation changes, especially on the face or neck (chloasma),
• painful red nodules on the skin (erythema nodosum),
• rash with target-shaped red lesions or erosions (erythema multiforme).

Reporting of adverse effects
If any adverse effects occur, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects can also be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: 22 49-21-301
Fax: 22 49-21-309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse effects allows the collection of additional information on the safety of the medicine.

5. How to store Ovestin

Keep the medicine out of the sight and reach of children.
Store at 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 month indicated.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Contents of the packaging and other information

What Ovestin contains
The active substance in Ovestin is estriol 0.5 mg. The other ingredient is: Witepsol S 58.
What the medicine looks like and contents of the pack
White, oval globules. Each blister contains 5 vaginal globules. Blisters are contained in a
cardboard box.
For more detailed information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in Romania, 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, The 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 in:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Marketing authorisation number in Romania, country of export: 3386/2011/01
Parallel import authorisation number: 210/19