Package Insert: Information for the User

Oestraclin0.6 mg/g Gel

Estradiol

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

It is used for:

To alleviate symptoms after menopause

During menopause (natural or surgically induced), the amount of estrogens produced by the woman's body decreases. This can cause symptoms such as hot flashes in the face, neck, and chest (“hot flashes”), nocturnal sweating, urogenital disorders (vulvovaginitis atrophy). Oestraclin alleviates these symptoms after menopause. This medication will only be prescribed if your symptoms seriously hinder 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 medications are not suitable for you, you may use this medication to prevent osteoporosis after menopause.

This medication should not be used to prevent heart disease or to improve intellectual capacity.

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

Medical History and Regular Check-Ups

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

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

Before starting (or restarting) THS, 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 will need to 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 Oestraclin.

Undergo regular breast check-ups, as recommended by your doctor.

Do not use Oestraclin

If any of the following points apply to you. If you are unsure about any of the following points, talk to your doctor before taking Oestraclin.

Do not take Oestraclin:

• If you areallergic(hypersensitive) to Estradiol or any of the other components of Oestraclin included in section 6 Additional Information;
• 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 arepregnantor suspect that you may be;
• If you haveabnormal vaginal bleeding;
• If you have anexcessive thickening of the uterine lining(endometrial hyperplasia) that is not being treated;
• If you have or have hadblood clots in a vein(thrombosis), for example in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism);
• If you have anyalteration that affects blood clotting(such as protein C deficiency, protein S deficiency, or antithrombin deficiency);
• If you have or have had recently a disease caused by blood clots in the arteries, such asangina pectoris, aheart attack, astroke, aretinal artery disease;
• If you have or have had any time 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 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 may cause skin irritation and dryness.

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

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

Before starting with hormone replacement therapy (HRT), 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 treatment.

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

• Any type of gynecological disorder
• Fibroids within the uterus
• Excessive 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 cancer sensitive to estrogens (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
• Galstones
• Migraines or intense headaches
• Autoimmune 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 especially careful not to exceed the recommended doses.

During HRT treatment, some serious diseases such as blood clots and certain types of tumors may appear more frequently.

Stop using Oestraclin and visit your doctor immediately.

If you notice any of the following symptoms while taking THS:

• Any of the conditions mentioned in the section "Do not use Oestraclin";
• Yellowing of the skin or the white of the eyes (jaundice). These may be signs of liver disease;
• Swelling of the face, tongue, and/or throat and/or difficulty swallowing or urticaria, along with difficulty breathing that are suggestive of angioedema;
• A sudden and significant increase in blood pressure (symptoms may include headache, fatigue, dizziness);
• Migraine-type headaches that occur for the first time;
• If you become pregnant
• If you observe signs of blood clots, such as:
• • Painful and swollen legs;
  • Sudden chest pain
  • Difficulty breathing;

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

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

HRT and Cancer

Endometrial hyperplasia and endometrial cancer

Using HRT with only estrogens will increase the risk of endometrial hyperplasia and 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 a uterus. If you have had your uterus removed (hysterectomy), consult your doctor to see if you can take this product safely without progestogen.

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

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

Unexpected Bleeding

You will have a bleed once a month (the so-called withdrawal bleed) while taking Oestraclin. However, if in addition to the monthly bleed you have an unexpected bleed or spots of blood that:

• Last longer than the first 6 months;
• Begin after having been using Oestraclin for more than 6 months;
• Continue after stopping Oestraclin;

Visit your doctor as soon as possible.

Thrombosis (Blood Clots)

HRT increases the risk of developing thrombosis (blood clots), and this risk is higher during the first year of use.

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

You are more likely to develop a blood clot in a vein as you age and if you have any of the following situations. Inform your doctor if you have any of these situations:

• You are unable to walk for a long time due to a major surgical procedure, an injury, or an illness (see also section 3, If you need to undergo a surgical procedure);
• You have severe obesity (BMI >30 kg/m2);
• You have any blood clotting disorder that requires long-term treatment with a medication used to prevent blood clots;
• Any of your close relatives have had a blood clot in a vein, lung, or other organ;
• You have systemic lupus erythematosus (SLE);
• You have cancer;

To know the signs of a blood clot, see "Stop taking Oestraclin and visit your 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 every 1,000 women will suffer a blood clot in a vein over a period of 5 years.

In the case of women aged 50 who have been taking HRT with estrogens-progestogens for more than 5 years, there will be 9 to 12 cases of every 1,000 users (i.e., 5 additional cases).

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

Cardiovascular Diseases (Heart Attack)

There is no evidence that HRT prevents heart attack.

Women over 60 who use HRT with estrogens and progestogens have a slightly higher probability of developing cardiovascular disease than those who do not take HRT.

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

Stroke

The risk of 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 every 1,000 will suffer a stroke over a period of 5 years. In the case of women aged 50 who take HRT, there will be 11 cases of every 1,000 users in 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.

HRT does not improve memory or intellectual capacity. 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

Inform your doctor or pharmacist if you are using or have used recently 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 forepilepsy(such as phenobarbital, phenytoin, and carbamazepine);
• Medications fortuberculosis(such as rifampicin, rifabutin);
• Medications forinfection with HIV(such as nevirapine, efavirenz, ritonavir, and nelfinavir);
• Medications based on plants that containSt. 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 liver function test results (elevated ALT enzyme) in women using CHC containing ethinylestradiol. Oestraclin contains estradiol instead of ethinylestradiol. It is unknown whether an increase in the ALT enzyme can occur when using Oestraclin with this HCV regimen;
• An anti-inflammatory (phenylbutazone);
• Antibiotics and other anti-infective medications (e.g., erythromycin, ketoconazole);
• Some anti-ulcer medications (cimetidine)

The effect of these last preparations remains for up to two weeks after stopping them.

Inform your doctor or pharmacist if you are using or have used recently other medications, even those acquired 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 area of your skin where the estradiol has been applied and cover the area, if necessary, after the spray/gel has dried. If a child comes into contact with the area of your skin where estradiol has been applied, wash the skin with water and soap as soon as possible. Due to the transfer of estradiol, young children may exhibit signs of unexpected puberty (e.g., the appearance of breasts). In most cases, symptoms will disappear when children stop being exposed to estradiol in spray/gel.

Contact your doctor if you observe any signs or symptoms (breast development or other sexual changes) in a child who may have been accidentally exposed to estradiol in spray/gel.

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Pregnancy and Breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

Do not use Oestraclin if you are pregnant or want to become pregnant.

Do not use Oestraclin if you are breastfeeding.

Driving and Operating Machinery

Your use does not affect your ability to drive vehicles and operate machinery. .

Follow exactly the administration instructions of this medication as 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 followed faithfully according to the medical prescription.

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, that is, one 2.5 g measure from the applicator, from 21 to 31 days per month.

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

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

The dosage 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 added normally during 12 or 14 days of the cycle.

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

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

This cycle will be repeated successively for several months, according to the doctor's indication. Since it is a replacement treatment, it usually lasts for a long time.

The administration ofthis medicationshould be done by the same patient, in the morning or at night.

How to use the tube and the applicator:

It is preferable to apply the gel once a day, always at the same hour and after bathing (the skin must be clean, dry and without cuts or other skin lesions).

To measure a daily dose of 2.5 g:

• Twist the applicator onto the tube mouth.
• Press 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, a 80 g tube will allow approximately 25 measures from the applicator.

Form of use:

Spread the gel over a wide area so that it is completely absorbed in about 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 FACE OF THE ARMS
• ABDOMEN
• INNER FACE OF THE THIGHS

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 medication, it is unlikely that an overdose will occur, but 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 Toxicological Information Service, phone(91) 562 04 20, indicating the medication and the amount ingested.

If you forgot to use Oestraclin

• If more than 12 hours are left before the next dose, apply the gel as soon as you remember and apply the next dose at the usual time.
• If less than 12 hours are left before the next dose, skip the missed dose and apply the next dose at the usual time.
• Do not use a double dose (two doses at the same time) to compensate for the missed 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 medication. You may need to stop using it for 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.

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

The following diseases are reported more frequently in women who use THS compared to women who do not use THS:

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

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

Adverse reactions are listed below classified by frequency according to the following criterion:

Frequent (may affect up to 1 in 10 people)

Rare (may affect up to 1 in 100 people)

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

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

Thromboembolic disorders, such as deep vein thrombosis and pulmonary embolism, are more frequent among THS 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 prospectus. You can also report them directly through the Spanish System for the Vigilance of Medicinal Products for Human Use: www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication

No special conservation conditions are required.

Keepthis medicationout of the sight and reach of children.

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

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE point of the pharmacy. Ask your pharmacist how to dispose of packaging and medications you no longer need. This will help protect the environment.

Composition of Oestraclin

• The active principle is estradiol. Each gram of gel contains 0.6 mg of estradiol.
• The other components (excipients) are: carbomers, trolamine, ethanol at 96% and purified water.

Appearance of Oestraclinand contents of the packaging

Transparent and colorless gel.

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

Holder of the marketing authorization and responsible for manufacturing

SEID, S.A.

Carretera de Sabadell to Granollers, Km. 15

08185 - Lliçà de Vall (Barcelona)

Last review date of this leaflet: June 2024

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