Ovestin

Package leaflet: Information for the user

Warning! Keep the leaflet, information on the immediate packaging in a foreign language!
Ovestin
1 mg/g, vaginal cream
Estriol
Please read the entire leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you may read it again if necessary.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it 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.

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 known as 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 affecting 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 inflammatory conditions with intense itching of the vagina. Estrogen deficiency may also cause urinary incontinence symptoms and recurrent urinary bladder infections. These symptoms 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 only after several days or even weeks.

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

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

2. Important information before using Ovestin

Medical history and regular check-ups
Hormone replacement therapy (HRT) involves risks that should be considered when deciding whether to start or continue HRT.
Experience with treatment in women who have premature menopause (due to ovarian failure or surgical removal of ovaries) is limited. In women with premature menopause, the risks associated with HRT may differ. Always consult your doctor.
Before starting (or restarting) 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 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 you are unsure, 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 of the pack and other information").
• if you currently have or have had breast cancer or if breast cancer is suspected.
• if you currently have or have had an estrogen-dependent tumor, such as 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 ever 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 ever had liver disease, 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 using the medicine 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 these symptoms may recur or worsen during treatment with Ovestin. If this happens, you should have more frequent check-ups:

• uterine fibroids (leiomyoma)
• endometriosis (growth of endometrial-like tissue outside the uterus) or previous excessive growth of the lining of the uterus (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 tumor
• diabetes with or without vascular complications
• gallstones
• migraine or severe headache
• 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 bones and causing hearing loss)
• fluid retention associated with 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 health while using Ovestin.
Stop using Ovestin and contact your doctor immediately if any of the following symptoms occur during HRT:

• any of the conditions listed in the section "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)
• first occurrence of migraine-type headaches
• pregnancy
• symptoms suggesting blood clot formation, 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 lining of the womb (endometrial hyperplasia) and cancer of the lining of the womb (endometrial cancer)
Long-term use of estrogen-only HRT in tablet form may increase the risk of developing cancer of the lining of the womb (endometrium).
It is not certain whether a similar risk exists with repeated or long-term (longer than one year) use of Ovestin. However, Ovestin has been shown 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. It may be a sign of endometrial thickening.
To prevent stimulation of 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 medicines used in hormone replacement therapy (HRT) that enter the bloodstream. Ovestin, however, is applied locally in the vagina 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 use, 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 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 consult 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 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 5 years. 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 or circulatory system
Blood clots in veins (venous thromboembolism)
The risk of blood clots in veins is about 1.3 to 3 times higher in women using HRT than in those who do not, especially during the first year of treatment.
Venous 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 the situations listed below 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 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 who do not use HRT, venous thrombosis can be expected in 4 to 7 out of 1000 women over 5 years.
Among women over 50 years of age who have used estrogen-only HRT for more than 5 years, the number of cases will be 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 about 1.5 times higher in women using HRT than in those who do not. The number of additional stroke cases associated with HRT use increases with age.
Comparison
Among women over 50 years of age not using HRT, stroke can be expected in about 8 out of 1000 women over 5 years, 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 conditions
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 or have recently taken, including medicines you plan to take, even those available without a prescription, 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 the action of 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 exclusively for use in postmenopausal women.
If you become pregnant, stop using Ovestin and consult 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.
Ovestin contains cetyl alcohol and stearyl alcohol.
This medicine may cause local skin reactions (e.g. contact dermatitis).

3. How to use Ovestin

This medicine should always be used exactly as your doctor or pharmacist has advised. If in doubt,
consult your doctor or pharmacist.
For atrophic changes in the lower urogenital tract, the recommended dose is
1 application daily for the first few weeks (maximum 4 weeks), after which the dose should be
gradually reduced to 1 application twice a week.
To improve wound healing in postmenopausal women who have undergone vaginal procedures,
the recommended dose is 1 application daily for 2 weeks before the procedure and 1 application twice
a week for 2 weeks after the procedure.
To facilitate interpretation of cervical smear results in postmenopausal women, the recommended
dose is 1 application every other day during the week preceding the smear test.
Ovestin cream should be administered intravaginally using the applicator, preferably before going to
bed.
1 application (applicator filled to the circular mark) contains 0.5 g of cream, corresponding to
0.5 mg of estriol.

1. Remove the cap from the tube, turn it upside down and use the pointed end to pierce the seal.
2. Screw the applicator onto the tube. Ensure the plunger is fully inserted into the applicator.

3. Slowly squeeze the cream into the applicator until resistance is felt (the plunger will stop at the position marked by the red ring indicated by arrows in the illustration below).

4. Unscrew the applicator from the tube and replace the cap on the tube.
5. In a lying position, insert the applicator tip containing the cream deeply into the vagina.
6. Slowly push the entire cream content into the vagina by pressing the plunger.

7. After use, remove the plunger from the applicator by overcoming the resistance point and wash both parts thoroughly with warm water and soap. Do not use detergents. After washing, rinse both parts well. DO NOT PLACE THE APPLICATOR IN HOT OR BOILING WATER.
8. The device can be reassembled by inserting the plunger into the applicator, overcoming the resistance point.

After the tube is empty, the applicator should be discarded.
Your doctor will aim to prescribe the lowest possible dose, to be used for the shortest duration necessary to relieve symptoms.
If you feel that the effect of Ovestin is too strong or too weak, consult your doctor.
Use of a higher than recommended dose of Ovestin
If a higher than recommended dose is used, consult your doctor or pharmacist immediately.
Accidental ingestion of the cream 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 a dose is missed, take it as soon as possible, unless the next scheduled dose is due the following day. If the missed dose is noticed on the day of the next scheduled application, skip the missed dose and continue with the previously established dosing schedule.
Need for 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 venous thrombosis (see section 2, "Blood clots in veins"). Ask your doctor when you can 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 all medicines, this medicine can cause adverse effects, although not everyone experiences them.
The following conditions are reported more frequently in women using systemic hormone replacement therapy (HRT) – i.e. HRT administered in a way that allows it to enter the bloodstream – compared to women not using HRT. These risks are less relevant for locally administered medicines, such as Ovestin:

• ovarian cancer
• 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 further information on these adverse effects, see section 2.

Depending on the dose used and individual patient sensitivity, the following adverse effects 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 effects have been reported during the use of other HRT medicines:

• 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-shaped redness or ulceration (erythema multiforme).

Reporting of adverse effects
If any adverse effects occur, including those not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department for 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 helps to provide more information on the safety of the medicine.

5. How to store Ovestin

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer packaging after
"Expiry date (EXP)" and on the tube after "EXP".
Do not store above 25°C. Do not freeze.
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 pack and other information

What Ovestin contains

• The active substance in Ovestin is estriol. One gram of cream contains 1 mg of estriol.
• Other ingredients are: octyldodecanol (eutanol G), cetyl palmitate, glycerol, cetyl alcohol, stearyl alcohol, polysorbate 60, sorbitan stearate, lactic acid, chlorhexidine hydrochloride, sodium hydroxide, purified water.

What the medicine looks like and contents of the pack
Ovestin is a white to almost white, homogeneous, smooth cream with a mild, characteristic odour.
It is supplied in an aluminium tube with a plastic cap, together with an applicator marked with the CE conformity symbol, packed in a cardboard box.
Pack size: 15 g of cream in a tube.
For further information, please contact the marketing authorisation holder 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
Aspen Bad Oldesloe GmbH
Industriestrasse 32-36
D-23843 Bad Oldesloe
Germany
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
Marketing Authorisation number in France, the country of export: 34009 329 691 7 3
Parallel Import Licence Number: 48/24