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 (Synapause-E), 1 mg/g, vaginal cream

Estriol
Ovestin and Synapause-E are different trade names for the same medicine.

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 necessary.
• In case of any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed to a specific person. It should not be given to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. 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 packaging 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 (estrogen). Ovestin is used in postmenopausal women, at least 12 months after the cessation of natural menstruation.
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 is the cause of painful intercourse and the occurrence of inflammatory conditions and severe itching of the vagina. Estrogen deficiency can also cause symptoms of urinary incontinence and recurrent urinary tract infections. These ailments 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 cream may also be used for:

• accelerating the healing of postoperative wounds in postmenopausal women who have undergone vaginal surgery
• 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 a risk 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 the use of HRT may be varied. You should always consult a doctor.
Before starting (or resuming) HRT, the doctor will collect a medical history of the patient's health and family diseases. They 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 associated with continuing Ovestin therapy with your doctor.
You should regularly perform breast examinations as recommended by your doctor.

When not to use Ovestin

Ovestin should not be used if any of the following situations apply to the patient. In case of uncertainty, before using Ovestin, you should consult a doctor.
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 breast canceris currently present or has occurred in the past, or 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 excessive thickening of the lining of the uterus(endometrial hyperplasia).
• If blood clots in blood vessels(venous thrombosis) are currently present or have occurred in the past, such as in the blood vessels of the legs (deep vein thrombosis) or lungs (pulmonary embolism).
• If there are blood clotting disorders(such as protein C deficiency, protein S deficiency, or antithrombin deficiency).
• If there are currently or recently arterial diseases caused by blood clots, such as heart attack, stroke, or angina pectoris.
• If there is currently or has been liver disease, and liver function test results have not returned to normal.
• If there is a rare blood disease called "porphyria", which is inherited by family members.

If any of the above health conditions occur for the first time while using Ovestin, you should stop the treatment immediately and consult a doctor without delay.

Warnings and precautions

Before starting treatment, you should inform your doctor if any of the following conditions are currently present or have occurred in the past, as they may recur or worsen during Ovestin treatment. If this happens, you should visit your doctor more frequently:

• uterine fibroids (leiomyoma)
• growth of endometrial cells outside the uterus (endometriosis) or a history of excessive growth of the uterine lining (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 mother, sister, or grandmother)
• high blood pressure
• liver disorders, such as a benign liver tumor
• diabetes with or without vascular complications
• gallstones
• migraine or severe headache
• immune system disease affecting multiple internal organs (systemic lupus erythematosus; chronic connective tissue disease with skin changes throughout the body)
• epilepsy
• asthma
• disease affecting the eardrum and causing hearing impairment (otosclerosis)
• fluid retention in the body due to heart or kidney disease.

You should 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. Taking these medications with some estrogen-containing medications may cause elevated liver function test results (increased ALT enzyme activity); the risk of this occurring with Ovestin is currently unknown.
You should tell your doctor if you notice any changes in your condition while using Ovestin.
You should stop using Ovestin and consult a doctor immediatelyif any of the following conditions occur during HRT use:

• any of the conditions listed in "When not to use Ovestin"
• yellowing of the skin and whites of the eyes (jaundice), which may be a sign of liver disease
• significant increase in blood pressure (which may manifest as headache, fatigue, dizziness)
• migraine-like headaches that occur for the first time
• pregnancy
• symptoms indicating the formation of blood clots, such as:
• painful swelling and redness of the legs
• sudden chest pain
• breathing difficulties. More information is provided in "Blood clots in veins (venous thrombosis)".

Note:Ovestin is not a contraceptive. If it has been less than 12 months since your last menstrual period or you are under 50 years old, you should use contraception to avoid pregnancy. You should consult a doctor.

HRT and tumors

Excessive thickening of the uterine lining (endometrial hyperplasia) and uterine lining cancer (endometrial cancer)

The use of estrogen-only HRT in tablet form for a long time may increase the risk of developing uterine lining cancer (endometrium).
It is not certain whether a similar risk exists with the repeated or long-term (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 progestogen is not necessary.
Bleeding or spotting should not normally be a cause for concern, but you should consult a doctor. This may be a sign of endometrial thickening.
To prevent endometrial stimulation, you should not exceed the maximum dose or take it for longer than a few weeks (up to 4 weeks).
The following risks are associated with HRT medications that enter the bloodstream. However, Ovestin is used locally vaginally and is absorbed into the bloodstream in very small amounts. It is less likely that the following conditions will worsen or recur during Ovestin treatment, but if you have any doubts, you should consult a doctor.

Breast cancer

Data indicate that the use of 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 consult a doctor if you notice any changes, such as:

• indentation or retraction of the skin
• changes in the nipples
• any visible or palpable thickening and/or lumps.

In addition, it is recommended to perform screening mammograms as advised by your 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 within 5 years in about 2 out of 2000 women. 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 circulatory system

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 it, especially in the first year of treatment.
Venous thrombosis can have a severe course. If a clot enters the lungs, it can cause chest pain, shortness of breath, fainting, or even death.
The likelihood of developing venous thrombosis increases with age and in the following situations. If any of the following situations apply to you, you should inform your doctor:

• prolonged immobilization due to major surgery, injury, or illness (see also section 3 "Need for surgery")
• significant obesity (body mass index over 30 kg/m)
• blood clotting disorders requiring long-term use of anticoagulant medications
• venous thrombosis in the legs, lungs, or other organs in a close relative
• systemic lupus erythematosus
• cancer.

Symptoms of venous thrombosis are listed in "When to 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 within 5 years.
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 (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
It is estimated that in women over 50 years old who do not use HRT, stroke will occur within 5 years in about 8 out of 1000 women, and in women of the same age using HRT, the rate will be 11 cases per 1000 women within 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. You should consult a doctor about this.

Ovestin and other medicines

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take, including those available without a prescription, herbal medicines, or other natural products.
Some medicines may affect the efficacy of Ovestin, and Ovestin may interfere with the action of other medicines, which can 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(such as nevirapine, efavirenz, ritonavir, and nelfinavir)
• herbal products containing St. John's Wort(Hypericum perforatum)

Laboratory tests

If blood tests are necessary, you should inform your doctor or laboratory staff that you are using 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 you become pregnant, you should stop using Ovestin and consult a doctor.
Women who are breastfeeding should consult a doctor before using Ovestin.

Driving and using machines

Using Ovestin should not affect your ability to drive or operate machines. However, individual reactions to the medicine may vary.

Ovestin cream contains cetyl alcohol and stearyl alcohol.

This may cause local skin reactions (e.g., contact dermatitis).

3. How to use Ovestin

This medicine should always be used as directed by your doctor or pharmacist. If you have any doubts, you should consult a doctor or pharmacist.
In the case of atrophic changes in the lower urinary and genital tracts, 1 application per day is usually used for the first weeks (up to 4 weeks), then the dose is gradually reduced to 1 application twice a week.
To improve wound healing in postmenopausal women who have undergone vaginal surgery, 1 application per day is usually used for 2 weeks before surgery and 1 application twice a week for 2 weeks after surgery.
To facilitate the interpretation of cervical smear results in postmenopausal women, 1 application every other day is usually used in the week preceding the smear.
Ovestin cream should be used vaginally with an applicator, preferably before going to bed at night.
1 application (applicator filled to the circular mark) contains 0.5 g of cream, which corresponds to 0.5 mg of estriol.

• 1. Remove the cap from the tube, turn it upside down, and open the tube with the sharp end.
• 2. Screw the applicator onto the tube. Make sure the plunger is fully inserted into the applicator.

• 3. Slowly squeeze the cream into the applicator until you feel resistance from the plunger (the plunger will stop at the point marked by the red ring indicated by the arrows in the figure below).

• 4. Unscrew the applicator from the tube and put the cap back on the tube.
• 5. In a lying position, insert the applicator tip with the cream deep into the vagina.

• 6. Slowly push the entire contents of the cream into the vagina using 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 PUT 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 try to prescribe the lowest possible dose that should be taken for the shortest time necessary to alleviate the symptoms.
If you feel that the effect of Ovestin is too strong or too weak, you should consult a doctor.

Using a higher dose of Ovestin than recommended

If a higher dose of Ovestin than recommended is used, you should consult a doctor or pharmacist immediately.
In the event of swallowing the cream, it does not pose a risk to health and life. Nevertheless, you should inform your doctor. Symptoms of overdose are usually nausea and vomiting; in women, menstrual bleeding may also occur a few days later.

Missing a dose of Ovestin

You should not take a double dose to make up for a missed dose.
If you miss a dose, you should take the medicine as soon as possible, unless you notice the miss on the day of the next application. If the miss is noticed on the day of the next application, you should skip the missed dose and continue with the previously established schedule.

Need for surgery

Individuals who are to undergo surgery should inform their 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)"). You should ask your doctor when you can start using Ovestin again.
If you have any further doubts about using this medicine, you should consult a doctor or pharmacist.

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

• ovarian cancer
• presence of 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:

• swelling and increased tenderness of the breasts
• mild vaginal bleeding
• increased vaginal discharge
• nausea
• fluid retention in the body, 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:

• inflammation of the gallbladder
• various skin disorders
• changes in skin pigmentation, especially on the face or neck (chloasma)
• painful red bumps on the skin (erythema nodosum)
• rash with plate-like, red lesions or ulcers (erythema multiforme).

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration 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, you can help gather more information 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 below 25°C. Do not freeze. Store in the original packaging to protect from light.
Do not use this medicine after the expiration date stated on the packaging. The expiration date refers to the last day of the specified month.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Ovestin contains

• The active substance of Ovestin vaginal cream is estriol in an amount of 1 milligram per 1 gram of cream (0.1%). The other ingredients are octyldodecanol, cetyl palmitate, glycerol, cetyl alcohol, stearyl alcohol, polysorbate 60, sorbitan stearate, lactic acid, chlorhexidine dihydrochloride, sodium hydroxide, and purified water.

What Ovestin looks like and what the packaging contains

Ovestin cream is a homogeneous, white or almost white mass. Ovestin is available in a 15 g aluminum tube. The cardboard box contains a tube with cream and an applicator marked with the CE conformity symbol.
For more detailed information, you should contact the marketing authorization holder or parallel importer.

Marketing authorization holder in the Netherlands, 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:

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
Netherlands marketing authorization number: RVG 08977

Parallel import authorization number: 130/22 Date of leaflet approval: 15.03.2022

[Information about the trademark]