Ovestins

Package leaflet: Information for the user

Warning! Keep this leaflet. The information on the immediate packaging is in a foreign language.
Ovestin (Physiogine), 0,5 mg, globules
Estriolum
Ovestin and Physiogine are different trade names for the same medicinal product.
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

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

Table of contents:

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 pack and other information

1. What Ovestin is and what it is used for

Ovestin belongs to a group of medicines called local oestrogen replacement therapy (HRT) for vaginal use. The medicine contains the female sex hormone estriol (an oestrogen). Ovestin is used in postmenopausal women, at least 12 months after the last natural menstrual period.

Ovestin is used to relieve menopausal symptoms in the vagina, such as dryness or irritation. This condition is medically known as "atrophic vaginitis". It is caused by a decrease in oestrogen levels in the body and occurs naturally after menopause.

If the ovaries are surgically removed before menopause (a procedure called oophorectomy), oestrogen production decreases rapidly.

A lack of oestrogen may cause dryness and increased sensitivity of the vaginal walls, leading to painful sexual intercourse, inflammation and intense vaginal itching. Oestrogen deficiency may also cause urinary incontinence and recurrent urinary bladder infections. These symptoms often improve with oestrogen-containing medicines. Noticeable improvement usually occurs within a few days or weeks of starting treatment.

Ovestin works by replacing the oestrogen normally produced by a woman's ovaries. The medicine is administered vaginally, so the hormone is released exactly where it is needed. This may 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 after vaginal surgery
• to facilitate accurate assessment of cervical smears in postmenopausal women

2. Important 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 have premature menopause (due to ovarian failure or surgical removal of the ovaries) is limited. In women with premature menopause, the risks associated with HRT may differ.
Always consult your doctor.
Before starting (or resuming) HRT, your doctor will take a detailed medical history, including family medical history. Your 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, you should have regular check-ups with your doctor (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing Ovestin treatment.
You should have regular breast examinations as recommended by your doctor.

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

Do not use Ovestin:

• if you are allergic to estriol or any of the other ingredients of this medicine (listed in section 6, "Contents of the pack and other information").
• if you currently have or have had breast cancer in the past, or if breast cancer is suspected.
• if you have an estrogen-dependent tumor, for example endometrial cancer (cancer of the lining of the womb), or if such a tumor is suspected.
• if you have vaginal bleeding of unknown cause.
• if you have untreated excessive thickening of the lining of the womb (endometrial hyperplasia).
• if you currently have or have 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 blood clot-related diseases, such as myocardial infarction (heart attack), stroke, or angina pectoris.
• if you currently have or have had liver disease in the past, and liver function test results have not returned to normal.
• if you have a rare inherited blood disorder called "porphyria".

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

Warnings and precautions
Before starting treatment, inform your doctor if you currently have or have ever had any of the following conditions, as they may recur or worsen during treatment with Ovestin. If this occurs, you should have more frequent check-ups:

• uterine fibroids (leiomyoma)
• endometriosis (growth of endometrial tissue outside the uterus) or previous excessive growth of the endometrium (endometrial hyperplasia)
• increased risk of blood clots [see section "Blood clots in veins (venous thromboembolism)"]
• increased risk of developing estrogen-dependent cancer (e.g. breast cancer in mother, sister, or grandmother)
• high blood pressure
• liver disorders, such as benign liver tumors
• diabetes with or without vascular complications
• gallstones
• migraine or severe headaches
• systemic autoimmune disease affecting multiple organs (systemic lupus erythematosus – SLE; chronic connective tissue disease with skin lesions throughout the body)
• epilepsy
• asthma
• otosclerosis (a disease affecting the ear bones and causing hearing loss)
• fluid retention due to heart or kidney disease
• hereditary or acquired angioedema.

Inform your doctor if you have hepatitis C and are being treated with medications such as ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin. Concurrent use of these drugs with certain estrogen-containing medicines may increase liver function test results (elevated liver enzyme ALT); the risk of this occurring with Ovestin is currently unknown.
Tell 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
• swelling of the face, tongue, and/or throat and/or difficulty swallowing or hives combined with breathing difficulties, suggesting angioedema
• significant increase in blood pressure (possible symptoms: headache, fatigue, dizziness)
• new-onset migraine-type headaches
• pregnancy
• symptoms suggesting blood clots, such as:
  • painful swelling and redness in the legs
  • sudden chest pain
  • difficulty breathing
    More information is provided in the section "Blood clots in veins (venous thromboembolism)".

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, you may need to use an additional method of contraception. Consult your doctor.

HRT and cancer

Excessive thickening of the womb lining (endometrial hyperplasia) and cancer of the womb lining (endometrial cancer)
Long-term use of oral estrogen-only HRT may increase the risk of developing cancer of the lining of the womb (endometrium).
It is uncertain 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 consult your doctor, as it may be a sign of endometrial thickening.
To avoid stimulating the endometrium, do not exceed the maximum dose or use it for longer than a few weeks (maximum 4 weeks).

The risks described below apply to systemic HRT medicines that enter the bloodstream. Ovestin, however, is applied locally in the vagina and is absorbed into the blood in very small amounts. It is less likely that the conditions listed below will worsen or recur during treatment with Ovestin, but if you have any doubts, consult your doctor.

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

You should have regular breast examinations and see your doctor if you notice any changes, such as:

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

Additionally, screening mammograms are recommended as advised by your doctor.

Ovarian cancer
Ovarian cancer is rare – much less common 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, about 2 out of 2,000 women will be diagnosed with ovarian cancer within 5 years. Among women who use HRT for 5 years, about 3 out of 2,000 women will be diagnosed (i.e. about 1 additional case).

Effects of HRT on the heart or circulatory system

Blood clots in veins (venous thromboembolism)
The risk of developing blood clots in veins is approximately 1.3 to 3 times higher in women using HRT than in women not using HRT, especially during the first year of treatment.
Blood clots can have serious consequences; 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. If any of these apply to you, inform your doctor:

• prolonged immobility 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 the legs, lungs, or another organ in a close relative
• systemic lupus erythematosus (SLE; chronic connective tissue disease with skin lesions throughout the body)
• cancer.

Symptoms of thrombosis are listed in the section "When to stop using Ovestin and contact your doctor immediately".

Comparison
Among women over 50 years of age not using HRT, about 4 to 7 out of 1,000 women can be expected to develop venous thrombosis within 5 years.
Among women over 50 years of age who have used estrogen-only HRT for more than 5 years, the number of cases is 5 to 8 per 1,000 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 it. The number of additional stroke cases associated with HRT use increases with age.

Comparison
Among women over 50 years of age not using HRT, about 8 out of 1,000 women can be expected to have a stroke within 5 years. Among women of the same age using HRT, the rate is 11 cases per 1,000 women within 5 years (i.e. 3 additional cases).

Other conditions
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 about this.

Ovestin and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take, including over-the-counter medicines, herbal remedies, or other natural products.
Some medicines may affect the action of Ovestin, leading to irregular bleeding. These include:

• 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 you need to have blood tests, 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 treatment with Ovestin.

Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, you should consult your doctor or pharmacist before using this medicine.
Ovestin is intended for use only in postmenopausal women. If you become pregnant, stop using Ovestin and contact your doctor.
Breastfeeding women should consult their doctor before using Ovestin.

Driving and using machines
Using Ovestin should not affect your 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. If you are unsure,
you should consult your doctor or pharmacist.

For atrophic changes in the lower urogenital tract, 1 suppository is usually used once daily for the first
weeks (up to a maximum of 4 weeks), then the dose is gradually reduced to 1 suppository twice a week.

To improve wound healing in postmenopausal women who have undergone vaginal procedures,
1 suppository is usually used daily for 2 weeks before the procedure and 1 suppository twice a week
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 test.

The suppository should be inserted deeply into the vagina while lying in a semi-reclining position,
before going to bed at night. The suppository must not be used rectally.

Your doctor will aim to prescribe the lowest possible dose, to 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 more Ovestin than prescribed
If you use more Ovestin than prescribed, contact your doctor or pharmacist immediately.
Accidental swallowing 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.

If you forget to use Ovestin
Do not use a double dose to make up for a forgotten dose.
If you forget a dose, use it as soon as possible, unless you notice the omission on the day the next
suppository is due. If the omission 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.

Need for surgery
If you are scheduled for surgery, you should inform the surgeon that you are using Ovestin. It may be
necessary to stop using the medicine approximately 4 to 6 weeks before surgery to reduce the risk of
blood clots (see section 2, "Blood clots in veins").
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 can cause adverse effects, although not everyone will experience them.
The following conditions are reported more frequently in women using systemic hormone therapy (HT)
medicines that enter the bloodstream than in women not using HT. These risks are less relevant to
topical medicines applied vaginally, such as Ovestin:

• ovarian cancer
• blood clots in the legs or lungs (venous thromboembolic disease)
• stroke
• possible memory loss if HT is started after the age of 65. For more information about these adverse effects, see section 2.

Depending on the doses used and individual patient sensitivity, the following adverse effects may occur:

• breast swelling and 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 will resolve after the first few weeks of treatment.
When using other HT medicines, the following adverse effects have been reported:

• inflammation of the gallbladder
• various skin disorders
  • skin discoloration, especially on the face or neck, known as "pregnancy mask" (chloasma)
  • painful red nodules on the skin (erythema nodosum)
  • rash with target-like redness or ulceration (erythema multiforme)

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects can 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 the medicine Ovestin

Keep this medicine out of the sight and reach of children.
Do not store above 25°C. 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 stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the packaging and other information

What the medicine Ovestin contains
The active substance in Ovestin is estriol. Each globule contains 0.5 mg of estriol.
Other ingredients: hard fat (containing polyethylene glycol stearate and glycerol ricinoleate).

What the medicine looks like and what the packaging contains
Ovestin is white, oval globules.
It is supplied in PVC/PE blisters in a cardboard box.
Pack size: 15 globules (3 blisters containing 5 globules each).
For more detailed information, please contact the responsible party or parallel importer.

Marketing Authorisation 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:
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 France, the country of export: 3400932969005
Parallel Import Licence Number: 66/21