Ovestin

Package Leaflet: Information for the User

Ovestin, 0.5 mg, pessaries

Estriol

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

• You should 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 Package 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 their last natural period.

Ovestin is used to relieve symptoms of menopause that occur in the vagina, such as dryness or irritation. In medical terms, this 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 inflammatory conditions and increased 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 ovaries in women. 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 for:

• accelerating the healing of postoperative wounds in 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 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, your 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 these check-ups, 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 you are unsure, 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").
• you have or have had breast cancer or there is a suspicion of breast cancer.
• you have or have had estrogen-dependent tumors, such as endometrial cancer (cancer of the lining of the uterus), or there is a suspicion of such a tumor.
• you have vaginal bleeding of unknown origin.
• you have untreated endometrial hyperplasia (thickening of the lining of the uterus).
• you have or have had blood clots in the blood vessels (venous thromboembolism), such as deep vein thrombosis or pulmonary embolism.
• you have blood clotting disorders (such as protein C, protein S, or antithrombin deficiency).
• you have or have recently had diseases caused by the presence of blood clots in the arteries, such as heart attack, stroke, or angina pectoris.
• you have or have had liver disease, and liver function tests have not returned to normal.
• you have a rare blood disease called porphyria, which is inherited through family members.

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 apply to you now or have applied in the past, as they may return or worsen during treatment with Ovestin. If this happens, you should visit your doctor more often:

• uterine fibroids (uterine leiomyoma)
• endometriosis (growth of endometrial tissue outside the uterus) or a history of endometrial hyperplasia
• increased risk of blood clots (see "Blood clots in the veins (venous thromboembolism)")
• increased risk of estrogen-dependent tumors (such as breast cancer in your mother, sister, or grandmother)
• high blood pressure
• liver disorders, such as liver tumors
• diabetes with or without vascular complications
• gallstones
• migraine or severe headaches
• systemic lupus erythematosus (SLE; a chronic disease affecting connective tissue with skin lesions)
• epilepsy
• asthma
• otosclerosis (a disease affecting the eardrum and causing hearing loss)
• fluid retention due to heart or kidney disease
• hereditary or acquired angioedema

Tell your doctor if you have hepatitis C and are taking 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 ALT enzyme 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:

• 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 with difficulty breathing, suggesting angioedema
• significant increase in blood pressure (possible symptoms include headache, fatigue, dizziness)
• migraine-like headaches 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 period or you are under 50, you may need to use an additional method of contraception. Consult your doctor.

HRT and Cancer

Endometrial Hyperplasia and Endometrial Cancer

Using estrogen-only HRT in tablet form for a long time may increase the risk of endometrial cancer.

It is not certain whether a similar risk exists with repeated or prolonged (longer than one year) use of Ovestin. However, it has been shown that Ovestin is absorbed into the bloodstream in very small amounts, and therefore, adding a progestogen is not necessary.

Bleeding or spotting is not usually a cause for concern, but you should consult your doctor. This 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).

The risks described below are associated with HRT medicines that enter the bloodstream. Ovestin, on the other hand, is used 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 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 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 Your Doctor If You Notice Any Changes, Such As:

• retraction of the skin
• changes in the nipple
• 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 between 50 and 54 years old 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 Blood Vessels

Blood Clots in the Veins (Venous Thromboembolism)

The risk of 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.

The formation of 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 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")
• severe obesity (body mass index over 30 kg/m2)
• blood clotting disorders that require long-term use of anticoagulant medications
• venous thromboembolism in the legs, lungs, or other organs in close relatives
• systemic lupus erythematosus (SLE; a chronic disease affecting connective tissue with skin lesions)
• cancer

Symptoms of venous thromboembolism 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 thromboembolism 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 (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 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 taking now or have taken recently, 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

Eating and drinking do not affect treatment with 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 in women after menopause only. 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 is unlikely to affect your ability to drive or use machines. However, individual reactions to the medicine may vary.

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.

For atrophic changes in the lower genital tract, Ovestin is usually used as 1 pessary per day for the first few weeks (up to 4 weeks), then the dose is gradually reduced to 1 pessary twice a week.

To improve wound healing in postmenopausal women who have undergone vaginal surgery, 1 pessary is usually used per day for 2 weeks before surgery and 1 pessary twice a week for 2 weeks after surgery.

To facilitate the interpretation of cervical smears in postmenopausal women, 1 pessary is usually used every other day in the week preceding the smear.

The pessary should be inserted deeply into the vagina in a recumbent position before going to bed. The pessary should not be used rectally.

Your doctor will try to prescribe the lowest dose that should be used for the shortest time necessary to relieve your symptoms.

If you feel that the action of Ovestin is too strong or too weak, ask your doctor.

Using More Ovestin Than Prescribed

If you have taken more Ovestin than prescribed, consult your doctor or pharmacist immediately.

If you have swallowed a pessary, it is not a danger to your health and life. However, you should tell your doctor about it. Symptoms of overdose are usually nausea and vomiting.

In women, after a few days, bleeding from the genital tract may also occur.

Missing a Dose of Ovestin

Do not use a double dose to make up for a missed dose.

If you miss a dose, use it as soon as you remember, unless it is time for your next dose. If you miss a dose and it is time for your next dose, skip the missed dose and continue with your regular schedule.

Need for Surgery

If you are going to have surgery, tell your surgeon that you 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 the 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 medicines used vaginally, such as 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 body, usually manifesting as swelling of the ankles or feet
• local irritation or itching
• flu-like symptoms

Most of these symptoms will disappear after a few weeks of treatment.

The following side effects have been reported in women using other HRT medicines:

• cholecystitis
• 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 red patches 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. You can also report side effects 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

You can also report side effects to the marketing authorization holder.

By reporting side effects, you can help provide 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 "EXP".

Store in a temperature between 2°C and 25°C. Protect from light and moisture.

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. Each pessary contains 0.5 mg of estriol.
• The other ingredients are: Witepsol S 58.

What Ovestin Looks Like and Contents of the Pack

Ovestin is a white, oval pessary.

It is available in PVC/PE blisters, in a cardboard box.

Package size: 15 pessaries (3 blisters of 5 pessaries each).

Marketing Authorization Holder

Aspen Pharma Trading Limited

3016 Lake Drive

Citywest Business Campus

Dublin 24, Ireland

tel: +48 22 104 21 00

Manufacturer

Unither Industries

Zone Industrielle Le Malcourlet

17 Avenue Des Portes Occitanes

Gannat, 03800, France

Date of Last Revision of the Leaflet:06/2024