Ovestin

Package Leaflet: Information for the User

Ovestin, 1 mg/g, Vaginal Cream

Estriol

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

Table of 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 pack 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. The medicine contains the female sex hormone estriol (estrogen). Ovestin is used in women after menopause, at least 12 months after the last natural menstrual period.
Ovestin is used to relieve symptoms of menopause that occur in the vagina, such as dryness or irritation. In medical terminology, this condition is called "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 can lead to painful intercourse and the occurrence of inflammation and severe itching of the vagina. Estrogen deficiency can also cause symptoms of urinary incontinence and recurrent urinary tract infections. These symptoms often disappear after using 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, so the hormone is released where it is needed.
This can relieve discomfort in the vagina.
Improvement may only be noticeable after a few days or even weeks.
In addition to the above indications, Ovestin may also be used to:

• accelerate wound healing after vaginal surgery in women
• facilitate the evaluation of cervical smears in postmenopausal women.

2. Important information before using Ovestin

Medical history and regular check-ups

Using HRT is associated with risks that need to be considered when deciding to start or continue hormone replacement 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 HRT may vary. You should always consult a doctor.
Before starting (or resuming) HRT, the doctor will take a medical history and may decide to perform a physical examination, including a breast examination and/or a gynecological examination.
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 of continuing Ovestin 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 conditions apply to you. If in doubt, consult your doctor before using Ovestin.
When not to use Ovestin:

• If any of the above conditions occur for the first time while using Ovestin, you should stop using it immediately and consult your doctor.

Warnings and precautions

Before starting treatment, tell your doctor if any of the following conditions currently exist or have existed in the past, as they may recur or worsen during Ovestin treatment. If this happens, you should visit your doctor more often:

• uterine fibroids (uterine leiomyoma)
• growth of endometrial cells outside the uterus (endometriosis) or a history of 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 liver tumors
• diabetes with or without vascular complications
• gallstones
• migraine or severe headache
• systemic 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 loss (otosclerosis)
• fluid retention due to heart or kidney disease
• hereditary and acquired angioedema.

Tell your doctor if you have hepatitis C and are being treated with medicines that include ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin. Taking these medicines with some estrogen-containing medicines may increase liver function test results (increase in liver enzyme ALT activity); the risk of this happening with Ovestin is currently unknown.
Tell your doctor if you notice any changes in your condition while using Ovestin.
Stop using Ovestin and consult your doctor immediatelyif you experience any of the following symptoms during HRT:

• 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
• swelling of the face, tongue, and/or throat, and/or difficulty swallowing or hives, in combination with difficulty breathing, which suggest angioedema.
• significant increase in blood pressure (possible symptoms include headache, fatigue, dizziness)
• migraine-like headaches that occur for the first time
• pregnancy
• symptoms of blood clots, such as:
• painful swelling and redness of the legs
• sudden chest pain
• difficulty breathing.

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

HRT and tumors

Endometrial hyperplasia and endometrial cancer

Using estrogen-only HRT in tablet form for a long time may increase the risk of developing endometrial cancer.
It is not certain whether a similar risk exists with 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 a progestogen is not necessary.
Bleeding or spotting is not usually a cause for concern, but you should consult your doctor. It may be a sign of endometrial hyperplasia.
To prevent endometrial stimulation, do not exceed the maximum dose or take it for longer than a few weeks (maximum 4 weeks).

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.

Check your breasts regularly and report any changes to your doctor, such as:

• indentation of the skin
• changes in the nipples
• any visible or palpable 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. Using 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 in about 2 out of 2000 women over 5 years. 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 circulation

Blood clots in veins (venous thrombosis)

The risk of developing blood clots in the veins is about 1.3 to 3 times higher in women using HRT than in those not using HRT, especially in the first year of treatment.
Developing blood clots can have serious consequences, and if a clot reaches the lungs, it can cause chest pain, shortness of breath, fainting, or even death.
The likelihood of developing blood clots in the veins increases with age and in the following situations. If any of these situations apply to you, tell 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/m²)
• blood clotting disorders that require long-term use of anticoagulant medications
• venous thrombosis in the legs, lungs, or other organs in a close relative
• systemic lupus erythematosus (SLE; chronic connective tissue disease with skin changes throughout the body)
• cancer.

Symptoms of venous thrombosis are listed in "When to stop using Ovestin and consult your doctor immediately".
Comparison
In women over 50 who do not use HRT, on average, 4 to 7 out of 1000 women can expect to develop venous thrombosis over 5 years.
In women over 50 who have 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 HRT. The number of additional stroke cases associated with HRT increases with age.
Comparison
In women over 50 who do not use HRT, on average, 8 out of 1000 women can expect to have a stroke over 5 years, and in women of the same age using HRT, this number is 11 out of 1000 women over 5 years (i.e., 3 additional cases).

Other conditions

HRT will 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 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 action of Ovestin, which can 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 to treat HIV(such as nevirapine, efavirenz, ritonavir, and nelfinavir)
• herbal products containing St. John's Wort(Hypericum perforatum)

Lab tests

If you need to have lab tests, tell your doctor or lab 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 action of Ovestin.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a baby, ask your doctor or pharmacist for advice before using this medicine.
Ovestin is intended for use only 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 using machines

Using Ovestin should not affect your ability to drive or use machines. However, individual reactions to the medicine may vary.
Ovestin contains cetyl alcohol and stearyl alcohol.
The medicine may cause local skin reactions (e.g., contact dermatitis).

3. How to use Ovestin

Always use this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist.
In the case of atrophic changes in the lower genital tract, the recommended dose is 1 application per day for the first weeks (maximum 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, the recommended dose is 1 application per day 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, the recommended dose is 1 application every other day in the week preceding the smear.
Ovestin cream should be used vaginally with an applicator, preferably before going to bed.
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 red ring indicated by the arrows in the drawing below).

• 4. Unscrew the applicator from the tube and put the cap back on the tube.
• 5. Lie down and 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, discard the applicator.
Your doctor will try to prescribe the lowest dose that will relieve your symptoms and will prescribe it for the shortest time necessary.
If you feel that the action of Ovestin is too strong or too weak, ask your doctor.

Using more Ovestin than recommended

If you use more Ovestin than recommended, consult your doctor or pharmacist immediately.
If you swallow the cream, it is not a danger to your health and life. However, you should inform your doctor. Symptoms of overdose are usually nausea and vomiting.
In women, after a few days, vaginal bleeding may also occur.

Missing a dose of Ovestin

Do not take a double dose to make up for a missed dose.
If you miss a dose, take it as soon as you remember, unless it is the day of the next application. If you miss a dose and it is the day of the next application, skip the missed dose and continue with the previously established schedule.

Need for surgery

People who are going to have surgery should tell 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"). Ask your doctor when you can start using Ovestin again.
If you have any further questions about using this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Ovestin can cause side effects, although not everybody gets them.
The following diseases are more frequently reported in women using HRT in the form of medicines that enter the bloodstream than in women not using HRT. These risks are less likely to apply to vaginally administered medicines like Ovestin:

• ovarian cancer
• blood clots in the veins of the legs or lungs (venous thromboembolism)
• stroke
• possible memory loss if HRT is started after the age of 65. More information on these side effects can be found in section 2.

Depending on the doses used and the patient's sensitivity, the following side effects may occur:

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

Most patients experience these symptoms disappearing after a few weeks of treatment.
The following side effects have been reported during the use of other HRT medicines:

• gallbladder inflammation
• various skin disorders
• skin discoloration, especially on the face or neck, known as "pregnancy spots" (chloasma)
• painful red lumps on the skin (erythema nodosum)
• rash with round redness or ulcers (erythema multiforme).

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, please tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, 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
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of this 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 packaging after "Expiry Date" and on the tube after "EXP".
Store below 25°C. Do not freeze.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Ovestin contains

• The active substance of Ovestin is estriol. One gram of cream contains 1 mg of estriol.
• The other ingredients are: octyldodecanol, cetyl palmitate, glycerol (E 422), cetyl alcohol, stearyl alcohol, polysorbate 60, sorbitan stearate, lactic acid, chlorhexidine dihydrochloride, sodium hydroxide, purified water.

What Ovestin looks like and contents of the pack

Ovestin is a white to almost white, homogeneous, smooth cream with a characteristic weak odor.
It is provided in an aluminum tube with a plastic cap, with an applicator marked with the CE conformity symbol, in a cardboard box.
Pack size: 15 g of cream in a tube.

Marketing authorization holder

Aspen Pharma Trading Limited
3016 Lake Drive
Citywest Business Campus
Dublin 24, Ireland
tel: +48 22 104 21 00

Manufacturer

Aspen Bad Oldesloe GmbH
Industriestrasse 32-36
D-23843 Bad Oldesloe
Germany

Date of last revision of the leaflet: