OVESTINON 0.5 mg VAGINAL SUPPOSITORIES

Introduction

Package Leaflet: Information for the User

Ovestinon 0.5 mg vaginal tablets

Estriol

Read this package leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the package leaflet

1. What is Ovestinon 0.5 mg vaginal tablets and what is it used for
2. What you need to know before you use Ovestinon 0.5 mg vaginal tablets
3. How to use Ovestinon 0.5 mg vaginal tablets
4. Possible side effects
5. Storing Ovestinon 0.5 mg vaginal tablets
6. Contents of the pack and other information

1. What is Ovestinon 0.5 mg vaginal tablets and what is it used for

Ovestinon belongs to a group of medicines called hormone replacement therapy (HRT). It contains the female hormone estriol (estrogen). Ovestinon is used in postmenopausal women who have had their last natural menstrual period at least 12 months ago.

It is used to relieve symptoms of menopause in the vagina, such as dryness or irritation. In medical terms, this is known as "vaginal atrophy". This is caused by a fall in estrogen levels in your body. This happens naturally after menopause.

If your ovaries are surgically removed (oophorectomy) before menopause, the decrease in estrogen production occurs very abruptly.

The lack of estrogen during menopause can cause the vaginal wall to become thin and dry (vaginal dryness). Therefore, sexual intercourse can become painful and may cause vaginal irritation and infections. The lack of estrogen can also lead to symptoms such as urinary incontinence and recurrent cystitis.

Ovestinon works by replacing the estrogen that is normally produced by the ovaries. It is inserted into your vagina, so the hormone is released where it is needed. This can relieve vaginal discomfort.

It may take several days or even weeks before you notice an improvement.

In addition to the uses mentioned above, Ovestinon may be used to:

• help heal wounds in postmenopausal women who have undergone vaginal surgery.

help with the study of the cervical smear (Pap test) in postmenopausal women.

2. What you need to know before you use Ovestinon 0.5 mg vaginal tablets

Medical history and medical examinations

The use of hormone replacement therapy involves risks that need to be considered when deciding whether to start treatment or continue it.

Experience with treatment in women with premature menopause (due to ovarian failure or surgical intervention) is limited. If you have premature menopause, consult your doctor, as the risks of using hormone replacement therapy may be different.

Before you start (or restart) hormone replacement therapy, your doctor will ask you about your medical history and that of your family. Your doctor may decide to perform a physical examination, which may include a breast examination and/or an internal examination, if necessary.

Once you have started taking Ovestinon, you should see your doctor for regular check-ups (at least once a year). During these check-ups, discuss the benefits and risks of continuing Ovestinon with your doctor.

Have regular mammograms as recommended by your doctor.

Do not use Ovestinon

If any of the following applies to you, or if you are not sure, consult your doctorbefore using Ovestinon.

Do not use Ovestinon:

• If you are allergic to estriol or any of the other ingredients of this medicine (listed in section 6).
• If you have or have had breast canceror if you suspect you might have it.
• If you have an estrogen-sensitive cancer, such as cancer of the lining of the uterus (endometrium), or if you suspect you might have it.
• If you have any unexplained vaginal bleeding.
• If you have excessive growth of the lining of the uterus(endometrial hyperplasia) that is not being treated.
• If you have or have had a blood clot in a vein(thrombosis), in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism).
• If you have a blood clotting disorder(such as protein C, protein S, or antithrombin deficiency).
• If you have or have had a disease caused by blood clots in the arteries, such as heart attack, stroke, or angina.
• If you have or have had a liver diseaseand your liver function tests have not returned to normal.
• If you have a rare blood disorder called porphyria that is inherited.

If any of the above conditions appear for the first time while taking Ovestinon, stop taking it immediately and consult your doctor.

Warnings and precautions

Consult your doctor before starting Ovestinon if you have had any of the following problems, as they may come back or get worse during treatment with Ovestinon. If so, you should see your doctor more often for medical check-ups:

• fibroids in the uterus,
• growth of the lining of the uterus outside the uterus (endometriosis) or a history of excessive growth of the lining of the uterus (endometrial hyperplasia),
• increased risk of developing blood clots (see "blood clots in a vein (thrombosis)"), increased risk of developing an estrogen-sensitive cancer (e.g., if your mother, sister, or grandmother has had breast cancer),
• high blood pressure,
• a liver disorder, such as a benign liver tumor,
• diabetes,
• gallstones,
• migraine or severe headaches,
• a disease of the immune system that affects many parts of the body (systemic lupus erythematosus, SLE),
• epilepsy,
• asthma,
• a disease that affects the eardrum and hearing (otosclerosis),
• fluid retention due to heart or kidney problems,
• hereditary and acquired angioedema.

Tell your doctor if you have hepatitis C and are taking the combination of medicines ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. The combination of these medicines with other medicines that contain estrogen may cause increases in blood tests of liver function (elevations of liver enzymes (ALT)). It is currently unknown whether this risk occurs with Ovestinon.

Stop using Ovestinon and see your doctor immediately

If you notice any of the following while taking hormone replacement therapy:

• any of the conditions mentioned in the "Do not use Ovestinon" section,
• yellowing of the skin or the whites of the eyes (jaundice), which may be a sign of liver disease,
• swelling of the face, tongue, or throat, and difficulty swallowing or hives accompanied by difficulty breathing, which suggest angioedema,
• a large increase in blood pressure (symptoms may be headache, tiredness, dizziness),
• migraine-like headaches that appear for the first time,
• • painful and swollen legs,
  • sudden chest pain,
  • difficulty breathing.

For more information, see "blood clots in a vein (thrombosis)".

Hormone replacement therapy and cancer

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

Taking HRT tablets that contain only estrogen for a long time may increase the risk of developing cancer of the lining of the uterus (endometrium).

It is not clear if there is a similar risk with Ovestinon used for repeated or long-term treatment (more than one year). However, it has been shown that the absorption of Ovestinon into the bloodstream is very low; therefore, the addition of a progestogen is not necessary.

If you bleed or spot, it is usually nothing to worry about, but you should make an appointment to see your doctor. It could be a sign that the endometrium has become thicker.

To avoid endometrial stimulation, do not exceed the maximum daily dose, and do not use this maximum dose for more than a few weeks.

The following risks apply to hormone replacement therapy medicines that circulate in the blood. However, Ovestinon is for local treatment in the vagina and its absorption into the blood is very low. It is less likely that the conditions mentioned below will get worse or come back during treatment with Ovestinon, but you should consult your doctor if you are concerned.

Breast cancer

Available data indicate that using Ovestinon does not increase the risk of breast cancer in women who have not had breast cancer in the past. It is not known if Ovestinon can be used safely in women who have had breast cancer in the past.

Check your breasts regularly. See your doctor if you notice any change, such as:

• dimpling of the skin,
• changes in the nipple,
• any lump that you can see or feel.

In addition, you are advised to participate in breast cancer screening programs when they are offered.

Ovarian cancer

Ovarian cancer is rare, much rarer than breast cancer. The use of HRT that contains estrogen only has been associated with a slightly increased risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women aged 50-54 who are not taking HRT, about 2 women in 2000 will be diagnosed with ovarian cancer over a 5-year period. For women who have been taking HRT for 5 years, there will be about 3 cases per 2000 users (i.e., about 1 extra case).

Effect of hormone replacement therapy on the heart and circulation

Blood clots in a vein

The risk of blood clots in the veinsis approximately 1.3 to 3 times higher in women using hormone replacement therapy than in those not using it, especially during the first year of treatment.

Blood clots can be serious, and if one travels to the lungs, it can cause chest pain, shortness of breath, fainting, or even death.

The likelihood of having a blood clot in the veins increases with age and if you are affected by any of the following conditions. Tell your doctor if any of these apply to you:

• you are unable to walk for a long time due to a major surgery, injury, or illness (see also section 3 "If you need to have surgery"),
• you are seriously overweight (BMI >30 kg/m2),
• you have a blood clotting disorder that requires long-term treatment with a medicine to prevent blood clots,
• a close relative has had a blood clot in the leg, lung, or other organ,
• you have systemic lupus erythematosus (SLE),
• you have cancer.

To know the signs of a blood clot, see the section "Stop using Ovestinon and see your doctor immediately".

Comparison

On average, 4 to 7 out of 1,000 women in their 50s who are not taking hormone replacement therapy may have a blood clot in a vein over a 5-year period. In women in their 50s who have been taking hormone replacement therapy that contains only estrogen for more than 5 years, there will be 5 to 8 cases per 1,000 users (i.e., 1 extra case).

Heart disease (heart attack)

Women taking only estrogen do not have an increased risk of developing heart disease.

Stroke

The risk of having a stroke is about 1.5 times higher in women using hormone replacement therapy than in those not using it. The number of extra stroke cases due to hormone replacement therapy increases with age.

Comparison

On average, 8 out of 1,000 women in their 50s who are not taking hormone replacement therapy may have a stroke over a 5-year period. In women in their 50s taking hormone replacement therapy for more than 5 years, there will be 11 cases per 1,000 users (i.e., 3 extra cases).

Other warnings

Hormone replacement therapy does not prevent memory loss. There is some evidence of a higher risk of memory loss in women who start hormone replacement therapy after the age of 65. Ask your doctor for advice.

Note:Ovestinon is not a contraceptive and should not be used as such. If it has been less than 12 months since your last menstrual period or you are under 50, you may still need to use a contraceptive method to prevent pregnancy. Ask your doctor for advice.

Other medicines and Ovestinon

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription, herbal medicines, or other natural products.

Some medicines may interfere with the effect of Ovestinon, or Ovestinon may interfere with the effect of other medicines. This could cause irregular bleeding. This occurs with the following medicines:

• Medicines for epilepsy(such as phenobarbital, phenytoin, and carbamazepine).
• Medicines for tuberculosis(such as rifampicin, rifabutin).
• Medicines for HIV infection(such as nevirapine, efavirenz, ritonavir, and nelfinavir).
• Herbal medicines that contain St. John's Wort(Hypericum Perforatum).

Tell your doctor if you have hepatitis C and are taking the combination of medicines ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. The combination of these medicines with other medicines that contain estrogen may cause increases in blood tests of liver function (elevations of liver enzymes (ALT)). It is currently unknown whether this risk occurs with Ovestinon.

Using Ovestinon with food and drink

You can eat and drink normally while taking Ovestinon.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Ovestinon should only be used by postmenopausal women. If you become pregnant, stop taking Ovestinon and contact your doctor.

If you are breastfeeding, consult your doctor before using Ovestinon, as it is excreted in breast milk.

Driving and using machines

Ovestinon is not expected to affect your ability to drive a car or operate machinery. However, individual responses to the medicine may vary.

Lab tests

If you need to have a blood test, tell your doctor or the laboratory staff that you are using Ovestinon, as this medicine may affect the results of some tests.

Ovestinon contains macrogol ceto-stearyl ether

Macrogol ceto-stearyl ether may cause local skin reactions (e.g., contact dermatitis).

3. How to use Ovestinon 0.5 mg ovules

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The recommended dose for vaginal discomfort is one ovule per day for the first few weeks (–maximum 4 weeks) and then the dose is gradually decreased to, for example, one ovule twice a week.

To improve wound healing in postmenopausal women undergoing vaginal surgery, the usual dose is one ovule daily for 2 weeks before surgery; after surgery, one ovule twice a week for 2 weeks.

To help evaluate vaginal smears in postmenopausal women, the usual dose is 1 ovule daily every day of the week before the test.

Your doctor may interrupt treatment every 2-3 months for a period of 4 weeks to assess whether it is necessary to continue.

For other situations, a different dose may be prescribed.

Instructions for the correct administration of the preparation

It is advisable to apply the ovule before going to bed. While in a lying position, an ovule will be inserted into the vagina as deeply as possible. The ovules are not intended for rectal insertion.

The maximum dose (1 ovule per day) should not be used for more than 2-3 weeks.

Your doctor will try to prescribe the lowest dose to treat your symptoms for the shortest necessary time. If you feel that the effect of Ovestinon is too strong or too weak, inform your doctor.

If you use more Ovestinon than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

In the case of accidental ingestion of some ovules, the symptoms that may appear are nausea and vomiting; in women and girls, vaginal bleeding may also occur after a few days.

If you forget to use Ovestinon

Do not use a double dose to make up for forgotten doses.

If you forget to administer a dose, do so when you remember, unless you realize on the same day that you are due for the next dose. In this case, do not administer it and simply apply the dose for that day in the usual way.

If you need to undergo surgery

If you are going to undergo surgery, inform the surgeon that you are using Ovestinon. You may need to stop using Ovestinon 4 to 6 weeks before the operation to reduce the risk of a blood clot (see section 2, Blood clots in a vein). Ask your doctor when you can start using Ovestinon again.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

4. Possible side effects

Like all medications, this medication can cause side effects, although not all people experience them.

In comparison with women who do not use hormone replacement therapy, the following diseases have been reported more frequently in women who use hormone replacement therapy that circulates in the blood. These risks affect fewer treatments administered via the vaginal route, such as Ovestinon:

• ovarian cancer,
• blood clots in the veins of the legs or lungs (venous thromboembolism),
• stroke,
• probable memory loss if hormone replacement therapy is started after the age of 65.

See section 2 for more information on these side effects.

Depending on the dose and the patient's sensitivity, Ovestinon may rarely cause side effects such as:

• swelling and increased sensitivity in the breasts.
• mild vaginal bleeding,
• increased vaginal discharge,
• nausea,
• fluid retention in tissues, usually marked by swollen ankles or feet,
• local irritation or itching,

And with unknown frequency:

• flu-like symptoms.

In most patients, these side effects disappear after the first few weeks of treatment.

The following side effects have been reported in association with other hormone replacement therapies.

• gallbladder disease,
• various skin disorders:

• skin pigmentation, especially on the face or neck, known as "pregnancy spots" (chloasma),
• painful and reddened nodules on the skin (erythema nodosum),
• skin rash with red lesions or papules in a target shape (erythema multiforme).

Reporting side effects:

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that is not listed in this prospectus. You can also report them directly through the Spanish Medication Surveillance System for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Conservation of Ovestinon 0.5 mg ovules

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging after "CAD.". The expiration date is the last day of the month indicated.

Do not store at a temperature above 25°C.

Keep in the original packaging to protect it from light and moisture.

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need at the SIGRE Point in the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Ovestinon

The active ingredient is estriol. Each ovule contains 0.5 mg of estriol.

The other components are semi-synthetic solid glycerides.

Appearance of the product and package contents

White torpedo-shaped ovules. Ovestinon is presented in boxes of 10 or 30 ovules for vaginal use. Each blister pack contains 5 ovules.

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Aspen Pharma Trading Ltd

3016 Lake Drive

Citywest Business Campus

Dublin 24

Ireland

Tel: 0034 952010137

Manufacturer

Unither Industries,

Zone Industrielle Le Malcourlet, 17 Avenue Des Portes Occitanes,

Gannat, 03800,

France

Local representative

Aspen Pharmacare España S.L.

Avenida Diagonal, 512

Planta Interior 1, Oficina 4

08006 Barcelona Spain

Date of the last revision of this prospectus:March 2024.

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/