Ovestin

Package leaflet: information for the patient

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

• 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 person. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

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 pack and other information

1. What is Ovestin and what is it 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 (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 a decrease in estrogen levels in the body and occurs naturally after menopause.

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

Estrogen deficiency may cause dryness and increased sensitivity of the vaginal walls, leading to painful sexual intercourse, inflammation, and intense vaginal itching. Estrogen deficiency may also cause urinary incontinence and recurrent bladder infections. These symptoms often improve 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 take several days or even weeks to become noticeable.

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

• to accelerate healing of postoperative wounds in women who have undergone vaginal surgery
• for 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 in treating women with premature menopause (due to ovarian failure or surgical removal of ovaries) is limited. In women with premature menopause, the risk associated with HRT may differ. Always consult your doctor.
Before starting (or resuming) HRT, your doctor will take a detailed medical history, including family history of diseases. Your doctor may also decide to perform a physical examination, including, if necessary, a breast and/or vaginal gynecological examination.
After starting 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 therapy.
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 conditions 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 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 lining of the uterus (endometrial hyperplasia).
• If you currently have or have ever had blood clots in blood vessels (venous thromboembolism), for example in the blood vessels of the legs (deep vein thrombosis) or in the lung vessels (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 ever had liver disease, and liver function tests have not returned to normal.
• If you have a rare inherited blood disorder called "porphyria".

If any of the above health 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 are currently present or have occurred previously, as they may recur or worsen during treatment with Ovestin. If this happens, more frequent medical check-ups may be necessary:

• Uterine fibroids (leiomyoma)
• Growth of endometrial tissue outside the uterus (endometriosis) 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)
• Hypertension
• Liver disorders, such as benign liver tumour
• Diabetes with or without vascular complications
• Gallstones
• Migraine or severe headaches
• 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 drum membrane and causing hearing loss)
• Fluid retention due to heart or kidney disease

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.
You should 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)
• First occurrence of migraine-type headaches
• Pregnancy
• Symptoms indicating blood clots, such as:
  • Painful swelling and redness of the legs
  • Sudden chest pain
  • Breathing difficulties
    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 should use contraception to avoid pregnancy. Consult your doctor.

HRT and cancer
Excessive thickening of the lining of the uterus (endometrial hyperplasia) and cancer of the uterine lining (endometrial cancer)
Long-term use of oral estrogen-only HRT increases the risk of developing cancer of the uterine lining (endometrium).
It is not certain whether this risk applies to 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 adding 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 avoid 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 HRT medicines that enter the bloodstream. However, Ovestin is applied locally via the vagina and is absorbed into the blood only in very small amounts. It is less likely that the conditions listed below will worsen or recur during treatment with Ovestin, but if in doubt, consult your doctor.

Breast cancer
Data indicate that using 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 contact your doctor if you notice any changes, such as:

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

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

Ovarian cancer
Ovarian cancer is rare – much rarer than breast cancer. Estrogen-only HRT is associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer depends on 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 users (i.e. about 1 additional case).

Effect of HRT on the heart or circulatory system
Blood clots in veins (venous thromboembolism)
The risk of venous blood clots is about 1.3 to 3 times higher in women using HRT than in those not using it, 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 venous blood clots increases with age and in the following situations. If any of the following 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 legs, lungs, or other organs 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
In women over 50 years of age not using HRT, venous thrombosis is expected in 4 to 7 out of 1000 women over a 5-year period.
In women over 50 using estrogen-only HRT for more than 5 years, the number of cases is 5 to 8 per 1000 women (i.e. 1 additional case).

Heart disease (myocardial infarction)
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 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 among 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 does not prevent memory loss. Some evidence suggests a higher risk of memory loss in women who start HRT after age 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 effectiveness of Ovestin, and Ovestin may affect the action of other medicines. This may lead 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 the effectiveness of Ovestin treatment.

Pregnancy and breastfeeding
Ovestin is intended for use only in postmenopausal women. If you become pregnant, stop using Ovestin and contact your doctor.
Women who are breastfeeding should consult their doctor before using Ovestin.

Driving and operating machinery
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 as directed by your doctor or pharmacist. If you have any doubts,
please consult your doctor or pharmacist.
For atrophic changes in the lower urogenital 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 who have undergone vaginal procedures,
1 suppository daily is usually used 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 deeply into the vagina while lying in a semi-reclining position
before going to bed at night. Do not use the suppositories rectally.
Your doctor will aim to prescribe the lowest possible dose for the shortest duration necessary to
relieve your symptoms.
If you feel that the effect of Ovestin is too strong or too weak, please consult your doctor.
Taking more Ovestin than recommended
If you use more Ovestin than recommended, 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.
Missing a dose of Ovestin
Do not use a double dose to make up for a missed dose.
If you miss a dose, take it as soon as possible, unless you notice the omission on the day when 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 your regular dosing schedule.
Need for surgery
If you are scheduled for surgery, inform your surgeon that you are using Ovestin. It may be necessary
to stop using this medicine approximately 4 to 6 weeks before surgery to reduce the risk of blood
clots (see section 2, "Venous blood clots"). 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 reactions

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

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

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

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

In most patients, these symptoms resolve after the first few weeks of treatment.
The following adverse reactions have been reported during 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 reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 adverse reactions helps provide more information on the safety of the medicine.

5. How to store Ovestin

Keep this medicine out of sight and reach of children.
Store below 25°C. Protect from light and moisture.
Do not use this medicine after the expiry date stated on the package.
Batch number and expiry date are embossed on the edge of the blister.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. These measures help protect
the environment.

6. Contents of the pack and other information

What Ovestin contains
The active substance is estriol 0.5 mg.
The other component is: Witepsol S 58.

What the medicine looks like and contents of the pack
White, oval globules. The pack contains 15 vaginal globules. PVC/PE blisters are contained
in a cardboard box.

For further detailed information, please contact the responsible entity or the 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:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź

Repackaged in:
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

French Marketing Authorisation Number (country of export): 34009 329 690 0 5
329 690-0
Parallel Import Licence Number: 228/18