OVESTINONE 1 mg/g VAGINAL CREAM

2. What you need to know before you start using Ovestinon 1 mg/g Vaginal Cream

Medical History and Medical Examinations

The use of hormone replacement therapy (HRT) involves risks that need to be considered when deciding whether to start treatment or continue taking 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 HRT 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 conditions apply to you, or if you are unsure about any of them, consult your doctorbefore using Ovestinon.

Do not use Ovestinon:

• If you are allergicto 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 may have it.
• If you have a cancer that is sensitive to estrogens, such as cancer of the tissue that lines the uterus (endometrium), or if you suspect you may have it.
• If you have any unexplained vaginal bleeding.
• If you have excessive growth of the tissue that lines 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 deficiency, protein S deficiency, or antithrombin deficiency).
• If you have or have recently 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 in families.

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

Warnings and Precautions

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

• fibroids in the uterus
• growth of the tissue that lines the uterus outside the uterus (endometriosis) or a history of excessive growth of the tissue that lines 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 had breast cancer)
• high blood pressure
• a liver disorder, such as a benign liver tumor,
• diabetes,
• gallstones,
• migraine or severe headaches,
• a disease that affects many organs in 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 estrogens may cause increases in liver function test results (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 section "Do not use Ovestinon",
• 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, fatigue, dizziness),

• migraine-like headaches that appear for the first time,
• painful swelling and redness of the 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 tissue that lines the uterus (endometrial hyperplasia) and cancer of the tissue that lines the uterus

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

It is not clear whether 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 stain, it is usually nothing to worry about, but you should schedule 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 (maximum 4 weeks).

The following risks apply to hormone replacement therapy (HRT) 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 worsen or reappear 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 whether 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 changes, 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 to you.

Ovarian Cancer

Ovarian cancer is rare: much rarer than breast cancer. The use of HRT that contains only estrogen 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 additional 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 who use hormone replacement therapy than in those who do not, 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 conditions apply to you:

• you are unable to walk for a long time due to major surgery, injury, or illness (see also section 3 "If you need to have surgery"),
• you are severely overweight (BMI > 30 kg/m2),
• you have a blood clotting disorder that requires long-term treatment with a medicine to prevent blood clots,
• if 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 taken 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 additional case).

Heart Disease (Heart Attack)

Women who are 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 who use hormone replacement therapy than in those who do not. The number of additional 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 who have taken hormone replacement therapy for more than 5 years, there will be 11 cases per 1,000 users (i.e., 3 additional 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 using 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 you had your last menstrual period or you are under 50, you may still need to use a contraceptive method to avoid becoming pregnant. 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 may 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 estrogens may cause increases in liver function test results (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 during treatment with Ovestinon.

Pregnancy, Breast-feeding, and Fertility

If you are pregnant or breast-feeding, 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 breast-feeding, 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.

Important Information about Some of the Ingredients of Ovestinon

This medicine may cause local skin reactions (such as contact dermatitis) because it contains cetyl alcohol and stearyl alcohol.

3. How to use Ovestinon 1 mg/g vaginal cream

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

Never exceed the dose that your doctor has prescribed for you.

The recommended dose for vaginal discomfort is one daily application during the first weeks (maximum 4 weeks) and then the dose is gradually decreased to, for example, one application twice a week.

To improve wound healing in postmenopausal women undergoing vaginal surgery, the usual dose is 1 daily application for 2 weeks before surgery and then 1 application twice a week for 2 weeks after surgery.

To help evaluate vaginal smears in postmenopausal women, the usual dose is 1 daily application 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

Use the applicator to apply the cream to the vagina. It is advisable to do this before going to bed.

One application (full applicator up to the mark) contains 0.5 g of Ovestinon cream, which in turn contains 0.5 mg of estriol.

1. Open the tube, invert the cap, and use the sharp tip to open the tube's seal.
2. Screw the applicator onto the tube. Make sure the plunger is completely inserted into the cylinder.

1. Squeeze the tube slowly so that enough cream enters the applicator to fill it up to the mark (red mark, see the dates in the drawing below).

1. Unscrew the applicator and reclose the tube.
2. To apply the cream, lie down and insert the end of the applicator deeply into the vagina.
3. Slowly push the plunger until the applicator is empty.

1. After use, remove the plunger from the cylinder by passing the point of resistance and wash it along with the applicator in warm soapy water, rinsing well afterwards. Do not use detergents. Rinse well after.

DO NOT PUT THE APPLICATOR IN HOT OR BOILING WATER.

1. The applicator can be reassembled by inserting the plunger completely into the cylinder, passing the point of resistance.

Discard the applicator once the tube is empty.

The maximum dose (1 application 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, let your doctor know.

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.

If someone ingests some of the cream, they should consult a doctor. 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:

• pseudoflu-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 reddish nodules on the skin (erythema nodosum),
• skin rash with reddish lesions or papules in a target shape (erythema multiforme).

Reporting of 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 Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Ovestinon 1 mg/g vaginal cream

Keep this medication out of the 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.

Store in the original packaging.

Do not store at a temperature above 25°C.

Do not freeze.

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 gram of cream contains 1 mg (milligram) of estriol.
• The other components are octyldodecanol, cetostearyl ester wax, glycerol (E-422), cetyl alcohol, stearic alcohol, polysorbate 60, sorbitan stearate, lactic acid, chlorhexidine dihydrochloride, sodium hydroxide, and purified water.

Appearance of the product and package contents

Homogeneous, smooth, white to almost white, creamy consistency. Ovestinon cream is presented in a box with a tube containing 15 g of cream and an applicator.

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

Aspen Bad Oldesloe GmbH

Industriestrasse 32-36

D-23843 Bad Oldesloe

Germany

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/