OESTRACLIN 0.6 mg/g GEL

Introduction

Package Leaflet: Information for the User

Oestraclin0.6 mg/g gel

Estradiol

Contents of the Package Leaflet:

1. What is Oestraclin and what is it used for
2. What you need to know before you start using Oestraclin
3. How to use Oestraclin
4. Possible side effects
5. Storage of Oestraclin
6. Package contents and further information

1. What is Oestraclin and what is it used for

Oestraclin is a hormone replacement therapy (HRT). It contains the female hormone estrogen. This medicine is used in postmenopausal women.

It is used to:

Relieve symptoms after menopause

During menopause (natural or surgically induced), the amount of estrogen produced by the woman's body decreases. This can cause symptoms such as hot flashes in the face, neck, and chest, night sweats, and urogenital disorders (atrophic vulvovaginitis). Oestraclin relieves these symptoms after menopause. This medicine will only be prescribed to you if your symptoms seriously affect your daily life.

Prevention of osteoporosis

After menopause, some women may develop bone fragility (osteoporosis). You should discuss all available options with your doctor.

If you have a higher risk of fractures due to osteoporosis and other medicines are not suitable for you, you can use this medicine to prevent osteoporosis after menopause.

This medicine should not be used to prevent heart disease or to increase intellectual ability.

This medicine is not a contraceptive, nor does it restore fertility.

2. What you need to know before starting to use Oestraclin

Medical history and periodic reviews

The use of HRT involves risks that must be taken into account when deciding whether to start using it or to continue using it.

Experience in the treatment of women with premature menopause (due to ovarian failure or surgery) is limited. If you have premature menopause, the risks of using HRT may be different. Talk to your doctor.

Before starting (or restarting) HRT, your doctor will ask you about your medical history and that of your family. Your doctor may decide to perform a physical examination. This may include an examination of your breasts and/or an internal examination, if necessary.

Once you have started using Oestraclin, you should go to your doctor for periodic reviews (at least once a year). In these reviews, discuss with your doctor the benefits and risks of continuing with Oestraclin.

Undergo periodic breast examinations, as recommended by your doctor.

Do not use Oestraclin

If any of the following points apply to you. If you are not sure about any of the following points, talk to your doctorbefore taking Oestraclin.

Do not take Oestraclin:

• If you are allergic(hypersensitive) to Estradiol or to any of the other components of Oestraclin included in section 6 Additional information;
• If you have or have had breast canceror if you suspect you may have it;
• If you have a hormone-sensitive cancer, such as uterine cancer (endometrium), or if you suspect you may have it;
• If you are pregnant or suspect you may be pregnant;
• If you have abnormal vaginal bleeding;
• If you have excessive thickening of the uterine lining(endometrial hyperplasia) that is not being treated;
• If you have or have had a blood clot in a vein(thrombosis), for example in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism);
• If you have any disorder that affects blood clotting(such as protein C, protein S, or antithrombin deficiency);
• If you have or have recently had a disease caused by blood clots in the arteries, such as angina pectoris, myocardial infarction, stroke, or eye artery damage;
• If you have or have had liver diseaseand your liver function tests have not returned to normal;
• If you have a rare blood disorder called "porphyria" that is inherited from parents to children (hereditary);

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

Warnings and precautions

Consult your doctor or pharmacist before starting to use Oestraclin.

As it is a hydroalcoholic solution, it should not be applied directly to mucous membranes. Frequent applications can cause skin irritation and dryness.

Visit your doctor regularly and at least once a year. Talk to your doctor at each visit about the need to adjust or continue treatment.

For the treatment of climacteric symptoms (before and during menopause), HRT should be started when symptoms affect the quality of life of the woman. In all cases, a careful assessment of the risks and benefits should be made at least annually, and HRT should only be continued while the benefits outweigh the risks. The administration of the lowest dose and the shortest treatment duration should always be considered.

Before starting hormone replacement therapy (HRT), you should inform your doctor about your personal and family medical history. Your doctor will perform a complete physical and gynecological examination before starting treatment and periodically throughout it.

Tell your doctor if you have ever had any of the following problems before starting treatment, as they may reappear or worsen during treatment with Oestraclin. If so, you should go to your doctor more often for reviews:

• Gynecological disorders of any kind
• Fibroids inside the uterus
• Growth of the uterine lining outside the uterus (endometriosis) or a history of excessive growth of the uterine lining (endometrial hyperplasia)
• Increased risk of developing blood clots (see "Blood clots in a vein (thrombosis)")
• Increased risk of developing a hormone-sensitive cancer (e.g., having a mother, sister, or grandmother who has had breast cancer)
• Changes or alterations in the breasts
• Very high levels of fat in the blood (triglycerides)
• High blood pressure
• Liver disorders, such as a benign liver tumor
• Diabetes
• Gallstones
• Migraines or severe headaches
• Immune system disease that affects many organs of the body (systemic lupus erythematosus, SLE)
• Epilepsy
• Asthma
• Disease that affects the eardrum and hearing (otosclerosis);
• Fluid retention due to heart or kidney problems
• Hereditary and acquired angioedema
• Pregnancy

Be careful not to exceed the recommended doses.

During hormone replacement therapy, some serious diseases such as blood clots (thrombosis) and some types of tumors may appear more frequently.

Stop using Oestraclin and go to the doctor immediately.

If you notice any of the following symptoms when taking HRT:

• any of the conditions mentioned in the section "Do not use Oestraclin";
• yellowing of the skin or the whites of the eyes (jaundice). These can be signs of liver disease;
• swelling of the face, tongue, and/or throat and/or difficulty swallowing or urticaria, along with difficulty breathing, which are suggestive of angioedema;
• a large increase in blood pressure (symptoms may be headache, fatigue, dizziness);
• migraine-type headaches that occur for the first time;
• if you become pregnant
• if you notice signs of blood clots, such as:
• • painful swelling and redness of the legs;
  • sudden chest pain
  • difficulty breathing;

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

Note:Oestraclin is not a contraceptive. If it has been less than 12 months since your last menstruation or you are under 50 years old, you may need to use additional contraceptive methods to avoid pregnancy. Consult your doctor.

HRT and cancer

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

Taking HRT with only estrogens will increase the risk of excessive thickening of the uterine lining (endometrial hyperplasia) and uterine lining cancer (endometrial cancer).

Using a progestogen in addition to estrogen for at least 12 days of each 28-day cycle will protect you from this additional risk. Therefore, your doctor will prescribe a progestogen separately if you still have your uterus. If you have had your uterus removed (hysterectomy), consult your doctor to see if you can safely take this product without a progestogen.

In women who still have their uterus and do not use HRT, endometrial cancer will be diagnosed in an average of 5 out of 1,000 between the ages of 50 and 65.

In the case of women aged 50 to 65 who still have their uterus and use HRT with only estrogens, between 10 and 60 women out of 1,000 will be diagnosed with endometrial cancer (i.e., between 5 and 55 additional cases), depending on the dose and duration of treatment.

Unexpected bleeding

You will have a monthly bleeding (so-called withdrawal bleeding) while taking Oestraclin. However, if in addition to monthly bleeding you have unexpected bleeding or spotting that:

• lasts for more than the first 6 months;
• starts after you have been using Oestraclin for more than 6 months;
• continues after you have stopped using Oestraclin;

go to your doctor as soon as possible

Thrombosis (blood clots)

Hormone replacement therapy increases the risk of blood clots (thrombosis), and this risk is greater during the first year of use.

Blood clots can block major blood vessels. If a blood clot forms in the deep veins of the legs, it can break loose and block the pulmonary arteries (pulmonary embolism). Similarly, blood clots can occur, although much less frequently, in the heart arteries (myocardial infarction, angina pectoris), in the cerebral arteries (cerebral thrombosis), or in the eyes (loss of vision or double vision).

If you identify the appearance of any possible signs of a blood clot, inform your doctor immediately. These symptoms include:

• Pain and swelling in one leg
• Sudden cough
• Severe chest pain and sometimes also arm pain
• Difficulty breathing
• Severe and unusual headache
• Vision problems (loss of vision, double vision)
• Difficulty speaking clearly
• Dizziness
• Seizures
• Weakness or numbness that affects one part of the body
• Difficulty walking or holding things

The risk of blood clots may increase temporarily if you need to be immobilized for a period due to surgery or another reason. Therefore, in these cases, you should consult your doctor, as it may be advisable to interrupt treatment until you fully recover your mobility. If you are going to undergo surgery and know in advance that you will be bedridden for a period, inform your doctor.

Breast cancer

Existing data show that the use of hormone replacement therapy (HRT) with estrogen-progestogen combinations or with only estrogens increases the risk of breast cancer.

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The additional risk depends on the duration of HRT use. The additional risk becomes apparent after 3 years of use. After stopping HRT, the additional risk will decrease over time, but the risk may persist for 10 years or more if HRT has been used for more than 5 years.

Your doctor will guide you on how to detect anomalies in your breast and will perform periodic checks throughout treatment.

Comparison

In women aged 50 to 54 who are not using HRT, an average of 13 to 17 out of 1,000 will be diagnosed with breast cancer over a 5-year period.

In women aged 50 who start hormone replacement therapy with only estrogens for 5 years, there will be between 16 and 17 cases per 1,000 women users (i.e., between 0 and 3 additional cases).

In women aged 50 who start taking HRT with estrogen-progestogen combinations for 5 years, there will be between 21 cases per 1,000 women users (i.e., between 4 and 8 additional cases).

In women aged 50 to 59 who are not taking HRT, an average of 27 cases of breast cancer will be diagnosed per 1,000 women over a 10-year period.

In women aged 50 who start hormone replacement therapy with only estrogens for more than 10 years, there will be 34 cases per 1,000 women users (i.e., 7 additional cases).

In women aged 50 who start HRT with estrogen-progestogen combinations for 10 years, there will be 48 cases per 1,000 users (i.e., 21 additional cases).

Regularly review your breasts. Go to 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. For mammography, it is important to inform the nurse or healthcare professional performing the X-ray that you are using HRT, as this medication can increase the density of your breasts, which can affect the result of the mammography. When breast density increases, it is possible that the mammography may not detect all lumps.

Ovarian cancer

Ovarian cancer is rare – much rarer than breast cancer. The use of HRT with only estrogens or with estrogen-progestogen combinations 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 to 54 who are not undergoing HRT, around 2 cases of ovarian cancer will be diagnosed per 2,000 women over a 5-year period. In women treated with HRT for 5 years, there will be around 3 cases per 2,000 patients (i.e., around 1 additional case).

Effects of HRT on the heart and circulation

Blood clots in a vein (thrombosis)

The risk of blood clots in the veinsis 1.3 to 3 times higher in HRT users than in non-users, especially during the first year of use.

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

It is more likely that you will develop a blood clot in your veins as you get older and if any of the following situations occur. Inform your doctor if any of these situations occur:

• you cannot walk for a long time due to major surgery, injury, or illness (see also section 3, If you need to undergo surgery);
• you are severely overweight (BMI >30 kg/m2);
• you have a blood clotting disorder that requires long-term treatment with a medication used to prevent blood clots;
• any of your close relatives have ever had a blood clot in the leg, lung, or other organ;
• you have systemic lupus erythematosus (SLE);
• you have cancer;

For information on the signs of a blood clot, see "Stop taking Oestraclin" and go to the doctor immediately"

Comparison

In the case of women aged 50 who do not take HRT, it is expected that, on average, 4 to 7 out of 1,000 women will suffer a blood clot in a vein over a 5-year period.

In the case of women aged 50 who have been taking HRT with estrogen-progestogen combinations for more than 5 years, 9 to 12 cases will occur per 1,000 users (i.e., 5 additional cases).

In the case of women aged 50 who have had their uterus removed and have been taking HRT with only estrogens for more than 5 years, 5 to 8 cases will occur per 1,000 users (i.e., 1 extra case).

Heart disease (myocardial infarction)

There is no evidence that HRT prevents myocardial infarction.

Women over 60 years old who use HRT with estrogens and progestogens have a slightly higher risk of suffering from heart disease than those who do not take HRT.

In the case of women who have had their uterus removed and take treatment based only on estrogens, there is no increased risk of developing heart disease.

Stroke

The risk of suffering a stroke is approximately 1.5 times higher in HRT users than in non-users. The number of additional stroke cases due to HRT use will increase with age.

Comparison

In the case of women aged 50 who do not take HRT, it is expected that, on average, 8 out of 1,000 will suffer a stroke over a 5-year period. In the case of women aged 50 who take HRT, 11 cases will occur per 1,000 users over 5 years (i.e., 3 additional cases).

Other conditions

Oestraclin is not a contraceptive and should not be used as such; it also does not restore fertility.

Hormone replacement therapy does not improve memory or intellectual ability. There is evidence of a higher risk of memory loss in women who start using HRT after the age of 65. Consult your doctor

Other medications and Oestraclin

Tell your doctor or pharmacist if you are using or have recently used or may need to use any other medication.

Some medications may interfere with the effect of Oestraclin. This could cause irregular bleeding. This applies to the following medications:

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

HRT may affect the functioning of other medications:

• A medication for epilepsy (lamotrigine), as it may increase the frequency of seizures;
• Medications for hepatitis C virus (HCV) (such as the combination regimen ombitasvir/paritaprevir/ritonavir with or without dasabuvir, as well as a regimen with glecaprevir/pibrentasvir) may cause increases in blood test results for liver function (increase in liver enzyme ALT) in women using CHC that contain ethinylestradiol. Oestraclin contains estradiol instead of ethinylestradiol. It is unknown whether an increase in liver enzyme ALT can occur when using Oestraclin with this combined HCV regimen;
• An anti-inflammatory (phenylbutazone);
• Antibiotics and other anti-infective medications (e.g., erythromycin, ketoconazol);
• Certain anti-ulcer medications (cimetidine)

The effect of these last preparations remains until two weeks after they have been stopped.

Tell your doctor or pharmacist if you are using or have recently used other medications, including those purchased without a prescription, herbal remedies, or other natural products. Your doctor will advise you.

Laboratory tests

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

Children

The estradiol in spray/gel can be accidentally transferred from the skin to other people. Do not allow others, especially children, to come into contact with the exposed area of your skin, and cover the area if necessary, after the spray/gel has dried. If a child comes into contact with the area of the skin where estradiol has been sprayed/applied, wash their skin immediately.

3. How to use Oestraclin

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

The dose should be established according to the blood hormone levels of each patient. The daily dose is variable (depending on each individual patient) and should be faithfully followed as prescribed by the doctor.

Your doctor will try to prescribe the lowest dose to treat your symptom for the shortest time necessary. Talk to your doctor if you think this dose is too strong or insufficient.

The normal dose is 2.5 g of gel per day, i.e., one 2.5 g measure of the applicator, for 21 to 31 days a month.

Your doctor may recommend other doses adapted to your specific case.

In patients with an intact uterus, estrogen should be supplemented, as indicated by the doctor, with the sequential administration of a progestogen, for at least the last 12 days of treatment with Oestraclin.

The posology can be cyclic when estrogen is dosed cyclically with a rest interval, normally 21 days of treatment and 7 days of rest. The progestogen is usually added for 12 or 14 days of the cycle.

The posology can be continuous sequential when estrogen is dosed continuously. The progestogen is usually added for at least 12-14 days of the 28-day cycle, sequentially.

The posology can be continuous combined when estrogen and progestogen are administered daily, without a rest period.

This cycle will be repeated successively for several months, as indicated by the doctor. Since it is a replacement treatment, it usually lasts quite a long time.

The administration of this medicine should be done by the same patient, in the morning or at night.

How to use the tube and applicator:

It is preferable to apply the gel once a day, always at the same time and after bathing (the skin should be clean, dry, and free of wounds or other skin lesions).

To measure a daily dose of 2.5 g:

• Screw the applicator onto the tube mouth.
• Squeeze the tube to fill the applicator with the gel, until the plunger stops at the 2.5 g mark.
• Separate the applicator from the tube and apply the gel to the skin.
• After each application, separate the plunger from the cannula and wash them.

At this dose, an 80 g tube will yield approximately 25 applicator measures.

Method of use:

Spread the gel over a large area so that it is fully absorbed in approximately two minutes. No massage or rubbing is necessary. Let it dry before dressing. Oestraclin does not smell or stain.

Correct application areas:

• NECK
• SHOULDERS AND INNER ARM
• ABDOMEN
• INNER THIGH

Areas where it should not be applied:

• BREASTS (Risk of swelling and pain)
• VULVOVAGINAL MUCOSA (Irritation and itching)

If you use more Oestraclin than you should

Consult your doctor or pharmacist immediately or go to the nearest hospital. Given the characteristics of this medicine, it is unlikely that an overdose will occur, although the administration of higher doses than necessary should be corrected by the doctor.

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 medicine and the amount ingested.

If you forget to use Oestraclin

• If there are more than 12 hours left until the next dose, apply the gel as soon as you remember and apply the next dose at the usual time.
• If there are less than 12 hours left until the next dose, skip the forgotten dose and apply the next dose at the usual time.
• Do not use a double dose (two doses at the same time) to make up for the forgotten dose. If you forget a dose, you may experience intermenstrual bleeding or spotting.

Do not allow others to touch the skin area where the spray/gel has been applied until it has dried and cover it with clothing if necessary.

If you need to undergo surgery

If you are going to undergo surgery, inform the surgeon that you are using this medicine. You may need to stop using it 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 Oestraclin again.

4. Possible side effects

Like all medicines, Oestraclin can cause side effects, although not everyone will experience them.

The following diseases are reported more frequently in women using HRT compared to women not using HRT:

• breast cancer;
• abnormal growth or cancer of the uterine lining (hyperplasia or endometrial cancer);
• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolism);
• heart disease;
• stroke;
• possible memory loss if HRT is started after age 65;

For more information on these side effects, see section 2.

Adverse reactions are listed below, classified according to their frequency, according to the following criteria:

Common (may affect up to 1 in 10 people)

Uncommon (may affect up to 1 in 100 people)

Rare (may affect up to 1 in 1,000 people)

Very rare (may affect up to 1 in 10,000 people)

Exceptional cases of chloasma or melasma that can be persistent, erythema multiforme, erythema nodosum, and hepatic adenoma have been reported in women treated with estrogens.

Venous thromboembolic disorders, i.e., deep vein thrombosis and pulmonary embolism, are more frequent among HRT users than among non-users.

If you experience any type of side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the Spanish Medicines Surveillance System for Human Use: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Oestraclin

No special storage conditions are required.

Keep this medicine out of the sight and reach of children.

Do not use Oestraclin after the expiration date shown on the box after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through wastewater or household waste. Deposit the containers and medicines you no longer need at the SIGRE point in the pharmacy. Ask your pharmacist how to dispose of the containers and medicines you no longer need. This will help protect the environment.

6. Package contents and additional information

Oestraclin composition

• The active ingredient is estradiol. Each gram of gel contains 0.6 mg of estradiol.
• The other ingredients (excipients) are: carbomers, tromethamine, 96% ethanol, and purified water.

Oestraclin appearance and package contents

Transparent and colorless gel.

It is presented in a tube with 80 g and a dosing applicator.

Marketing authorization holder and manufacturer

SEID, S.A.

Carretera de Sabadell a Granollers, Km. 15

08185 - Lliçà de Vall (Barcelona)

Date of last revision of this leaflet: June 2024

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