Package Insert: Information for the User

Ovestinon 0.5 mg Vaginal Tablets

Estriol

Read this entire package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others who may have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

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

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

If the ovaries are surgically removed (oophorectomy) before menopause, the drop in estrogen production occurs very suddenly.

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

Ovestinon acts by replacing the estrogen that is normally produced in the ovaries. It is inserted into the 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 earlier, Ovestinon could be used for:

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

helping with cervical smear (Papanicolau) testing in postmenopausal women.

Medical History and Medical Reviews

The use of hormone replacement therapy carries risks that must be taken into account when deciding whether to start treatment or continue taking it.

The experience of 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 starting (or restarting) hormone replacement therapy, your doctor will ask 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 visit your doctor for regular check-ups (at least once a year). In these check-ups, discuss with your doctor the benefits and risks of continuing with Ovestinon.

Have regular mammograms as recommended by your doctor.

Do not use Ovestinon

If you are affected by any of the following situations or have doubts about any of them, consult your doctor before using Ovestinon.Consult your doctorbefore using Ovestinon.

Do not use Ovestinon:

• If you are allergic to estriol or any of the other components of this medication (including those listed in section 6).
• If you have or have hadbreast canceror if you suspect that you may have it.
• If you have acancer sensitive to estrogens, such as endometrial cancer, or if you suspect that you may have it.
• If you have anyunexplained vaginal bleeding.
• If you haveexcessive growth of the endometriumthat is not being treated.
• If you have or have had ablood clot in a vein(thrombosis), in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism).
• If you have ablood clotting disorder(such as protein C deficiency, protein S deficiency or antithrombin deficiency).
• If you have or have had a disease caused by blood clots in the arteries, such asmyocardial infarction, stroke or angina pectoris.
• If you have or have had aliver 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 immediately.

Warnings and Precautions

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

• Fibroids in the uterus,
• Excessive growth of the endometrium outside the uterus (endometriosis) or a history of excessive growth of the endometrium (endometrial hyperplasia),
• Increased risk of developing blood clots (see “blood clots in a vein (thrombosis)), increased risk of developing a cancer sensitive to estrogens (for example, if your mother, a sister or an aunt have had breast cancer),
• High blood pressure,
• A liver disorder, such as a benign liver tumor,
• Diabetes,
• Galstones,
• Migraines 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.

Inform your doctor if you have hepatitis C and are taking the combined medication ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. The combination of these medications with other medications containing estrogens may cause increases in liver function test results (elevations of liver enzymes (ALT)). The risk of this occurring with Ovestinon is currently unknown.

Stop using Ovestinon and visit your doctor immediately

If you notice while taking hormone replacement therapy:

• Any of the conditions mentioned in the section “Do not use Ovestinon”,
• Yellowing of the skin or the white of the eyes (jaundice), which may be a sign of liver disease,
• Swelling of the face, tongue or throat and difficulty swallowing or urticaria accompanied by difficulty breathing, which suggests angioedema,
• A significant increase in blood pressure (symptoms may include headache, fatigue, dizziness),
• Severe headaches of a migrainous type that appear for the first time,
• If you become pregnant,
• If you experience signs of a blood clot, such as:
• • Painful and swollen legs,
  • Sudden chest pain,
  • Difficulty breathing.

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

Hormone Replacement Therapy and Cancer

Endometrial Hyperplasia and Endometrial Cancer

Using hormone replacement therapy tablets containing only estrogen for a prolonged period may increase the risk of developing endometrial cancer.

It is not clear if there is a similar risk with Ovestinon used for repeated or long-term treatments (more than one year). However, it has been shown that the absorption of Ovestinon in the blood 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, nor should you use this maximum dose for more than a few weeks.

The following risks affect medications that circulate in the blood. However, Ovestinon is for local treatment in the vagina and its absorption in the blood is very low. It is less likely that the conditions mentioned below will worsen or recur during treatment with Ovestinon, but you should consult your doctor if you are concerned.

Breast Cancer

The 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. Visit your doctor if you notice any changes such as:

• Moles on the skin,
• Changes in the nipple,
• Any lump that you can see or feel.

Additionally, you are recommended to participate in mammography screening programs when offered.

Ovarian Cancer

Ovarian cancer is rare:much rarer than breast cancer.Hormone replacement therapy containing 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 hormone replacement therapy, approximately 2 women out of every 2,000 will be diagnosed with ovarian cancer over a 5-year period. For women who have been taking hormone replacement therapy for 5 years, there will be around 3 cases per 2,000 users (i.e. around 1 case more).

Effect of Hormone Replacement Therapy on the Heart and Circulation

Blood Clots in a Vein

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

Blood clots can be serious, and if one dislodges and 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 have any of the following situations. Inform your doctor if you apply any of these situations:

• You are unable to walk for a prolonged period due to a major surgical intervention, injury or illness (see also section 3 “If you need to undergo a surgical intervention),
• You have a significant overweight (BMI>30 kg/m2),
• You have a blood clotting disorder that requires prolonged treatment with a medication 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 the presence of a blood clot, see the section “Stop using Ovestinon and visit your doctor immediately”.

Comparison

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

Cardiovascular Disease (Myocardial Infarction)

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

Stroke

The risk of stroke is around 1.5 times higher in women using hormone replacement therapy than in those who do not use it. The number of additional cases of stroke due to hormone replacement therapy increases with age.

Comparison

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

Other Warnings

Hormone replacement therapy does not prevent memory loss. There is some indication of a higher risk of memory loss in women who start using hormone replacement therapy after the age of 65 years. Consult your doctor.

Note:Ovestinon is not a contraceptive and should not be used as such. If you have had your last menstrual period less than 12 months ago or are under 50 years old, you may still need to use a contraceptive method to avoid becoming pregnant. Consult your doctor.

Other Medications and Ovestinon

Inform your doctor or pharmacist if you are using, have used recently or may need to use any other medication,including over-the-counter medications, herbal medications or other natural products.

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

• Medications forepilepsy(such as phenobarbital, phenytoin and carbamazepine).
• Medications fortuberculosis(such as rifampicin, rifabutin).
• Medications forHIV infection(such as nevirapine, efavirenz, ritonavir and nelfinavir).
• Herbal medications containingSt. John's Wort(Hypericum Perforatum).

Inform your doctor if you have hepatitis C and are taking the combined medication ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. The combination of these medications with other medications containing estrogens may cause increases in liver function test results (elevations of liver enzymes (ALT)). The risk of this occurring with Ovestinon is currently unknown.

Use of Ovestinon with Food and Beverages

You can eat and drink normally during treatment with Ovestinon.

Pregnancy, Lactation and Fertility

If you are pregnant orbreastfeeding, think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medication.

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 usingOvestinon, as it is excreted in breast milk.

Driving and Operating Machinery

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

Laboratory Tests

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

Ovestinon contains macrogol cetostearate

Macrogol cetostearate may cause local skin reactions (e.g. contact dermatitis).

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 dosefor vaginal discomfort is one tablet per day during the first weeks (–maximum 4 weeks) and then the dose is gradually reduced, for example, to one tablet two times a week.

For improving wound healing in postmenopausal women undergoing vaginal surgery, the usual dose is one tablet per day for 2weeks before surgery; after surgery, one tablet two times a week for 2weeks.

To help evaluate vaginal smears in postmenopausal women, the usual dose is one tablet per day every day of the week before the test.

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

For other situations, a different dose may be prescribed.

Instructions for correct administration of the preparation

It is recommended to apply the tablet before going to bed. While lying down, one tablet will be inserted into the vagina as deeply as possible. The tablets are not intended for insertion into the rectum.

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

Your doctor will try to prescribe the lowest dose to treat your symptoms for the shortest time necessary. 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 Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

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

If you forgot to use Ovestinon

Do not use a double dose to compensate for the missed doses.

If you forget to administer a dose, do it when you remember, unless you realize the same day that it is time for the next dose. In this case, do not administer it and simply apply the dose of 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 for 4 to 6weeks 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.

Like all medications, this medication may cause side effects, although not everyone will experience them.

Compared to women who do not use hormone replacement therapy, the following diseases have been reported more frequently in women using hormone replacement therapy that circulates in the blood..These risks affect fewer treatments administered vaginally, 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 patient sensitivity, Ovestinon may cause side effects such as:

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

And with unknown frequency:

• pseudogripal symptoms.

Most patients experience these side effects disappearingafter the first few weeks of treatment.

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

• gallbladder diseases,
• various skin disorders:

- skin pigmentation, especiallyon the face or neck, known as "pregnancy spots" (melasma),

-painful and reddish nodules on the skin (erythema nodosum),

- skin rash with lesions or papules in the shape of a target (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 does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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.

Do not store at a temperature above 25°C.

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

Medications should not be disposed of through drains or in the trash. Deposit the packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Ovestinon

The active principle is estriol. Each capsule contains 0.5 mg of estriol.

The other components aresemisynthetic solid glycerides.

Appearance of the product and contents of the packaging

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

Only some packaging sizes may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Aspen Pharma Trading Ltd

3016 Lake Drive

Citywest Business Campus

Dublin 24

Ireland

Tel: 0034 952010137

Responsible for manufacturing

Unither Industries,

Zone Industrielle Le Malcourlet,

03800 Gannat,

France

Local representative

Aspen Pharmacare España S.L.

Avenida Diagonal, 512

Ground Floor, Office 4

08006 Barcelona Spain

Last review date of this leaflet:March 2024.

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