Package Insert: Information for the User

Estradot 25 micrograms/24 hours Transdermal Patch

Estradiol (as hemihydrate)

Read this 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 or pharmacist.
• This medication has been prescribed for you only and should not be given to others who may have the same symptoms as you, as it may harm them.

-If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

1.What Estradot is and for what it is used

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

3.How to use Estradot

4.Possible side effects

5.Storage of Estradot

6.Contents of the package and additional information

Estradot is a Hormone Replacement Therapy (HRT) that contains the female sex hormone estrogen.

Estradot is used in postmenopausal women when at least 12 months have passed since their last natural menstrual period.

Estradot is presented as a patch that is applied to the skin.

Estradot is used for:

Relief of symptoms that appear during menopause

During menopause, the amount of estrogens produced by the woman's body decreases. This can cause symptoms such as sudden, severe hot flashes in the face, neck, and chest (hot flushes). Estradot relieves these symptoms after menopause. Estradot will only be prescribed if your symptoms seriously affect your daily life.

Medical History and Regular Reviews

The use of THS involves risks that should be considered when deciding to use it or to continue treatment.

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. Please consult your doctor.

Before starting (or resuming) THS, your doctor will ask you about your personal and family medical history. Your doctor may decide to perform a physical examination. This may include a breast examination and/or an internal examination, if necessary.

Once you start treatment with Estradot, you should visit your doctor for regular reviews (at least once a year). In these reviews, discuss with your doctor the benefits and risks of continuing with Estradot.

Perform regular breast checks, as recommended by your doctor.

Do Not Use

if any of the following apply to you. If you are unsure about any of the points described below, consult your doctor before using Estradot.

Do not use Estradot:

• if you have or have hadbreast cancer, or if there is suspicion that you may have it;
• if you have acancer that depends on estrogen, such as endometrial cancer, or if there is suspicion that you may have it;
• if you haveabnormal vaginal bleeding;
• if you have anexcessive thickening of the uterine wall.(endometrial hyperplasia) for which you are not receiving treatment;
• if you have or have had the formation of ablood clot in a vein(thrombosis), such as 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 recently a disease caused by blood clots in the arteries, such as aheart attack, astroke, or aangina;
• if you have or have had aliver diseaseand your liver function tests have not normalized;
• if you have a rare blood disease calledporphyriathat is inherited;
• if you areallergic(hypersensitive) to estradiol, or to any of the other components of this medication (including those listed in section 6 Container and additional information);

If you experience any of the conditions mentioned above for the first time while using Estradot, stop treatment immediately and consult your doctor immediately.

Warnings and Precautions

Inform your doctor if you have or have had any of the following situationsbefore starting treatment, as they may recur or worsen during Estradot treatment. In that case, you should visit your doctor more frequently for regular reviews:

• fibroids within the uterus;
• growth of the uterine wall outside the uterus (endometriosis) or history of excessive growth of the uterine wall(endometrial hyperplasia);
• increased risk of developing blood clots(see “Blood clots in a vein (thrombosis)”;
• increased risk of developing a cancer that depends on estrogen (such as breast cancer);
• increased blood pressure;
• liver disease, such as a benign tumor in the liver;
• diabetes;
• gallstones (biliary calculi);
• severe migraine or headache;
• a disease of the immune system that affects several organs of the body (systemic lupus erythematosus, SLE);
• epilepsy;
• asthma;
• a disease that affects the eardrum and ear (otosclerosis);
• very high levels of fat in your blood (triglycerides);
• fluid retention due to heart or kidney problems;
• hereditary and acquired angioedema.

Stop using Estradot and see a doctor immediately.

If you experience any of the following situations while using THS:

• any of the conditions mentioned in the section ‘Do Not Use Estradot’
• yellowing of the skin or white of the eyes (jaundice). This 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;
• 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 notice 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)”.

Note: Estradot is not a contraceptive. If you have had your last menstrual period less than 12 months ago or are less than 50 years old, you may still need additional contraceptive measures to prevent pregnancy. Consult your doctor for advice.

THS and Cancer

Thickening of the uterine wall (endometrial hyperplasia) and uterine cancer (endometrial cancer)

The use of THS with estrogen-only products will increase the risk of developing thickening of the uterine wall (endometrial hyperplasia) and uterine cancer (endometrial cancer).

The addition of a progestogen to estrogen treatment 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), ask your doctor if you can be treated with this medication safely without using a progestogen.

In women aged 50-65 years who still have a uterus and are not being treated with THS, a mean of 5 out of 1000 will be diagnosed with endometrial cancer.

In the case of women aged 50-65 years with a uterus and being treated with THS with estrogen-only products, between 10 and 60 women out of 1000 will be diagnosed with endometrial cancer (i.e., between 5 and 55 additional cases), depending on the dose and duration of therapy.

Unexpected Bleeding

You will experience bleeding once a month (called menstrual bleeding) while using Estradot in combination with a progestogen. However, if you experience unexpected bleeding or spotting apart from your monthly bleeding, which:

see your doctor as soon as possible.

Breast Cancer

The evidence shows that the use of hormone replacement therapy (HRT) with a combination of estrogen-progestogen or with estrogen-only products increases the risk of breast cancer. 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 you have used HRT for more than 5 years.

Comparison

In women aged 50-54 years who are not using HRT, a mean of 13 to 17 out of 1000 will be diagnosed with breast cancer over a 5-year period.

In women aged 50 years who start HRT with estrogen-only products for 5 years, there will be between 16 and 17 cases per 1000 users (i.e., between 0 and 3 additional cases).

In women aged 50 years who start HRT with a combination of estrogen-progestogen for 5 years, there will be 21 cases per 1000 users (i.e., between 4 and 8 additional cases).

In women aged 50-59 years who are not taking HRT, a mean of 27 cases of breast cancer per 1000 women can be expected over a 10-year period.

In women aged 50 years who start HRT with estrogen-only products for 10 years, there will be 34 cases per 1000 users (i.e., 7 additional cases).

In women aged 50 years who start HRT with a combination of estrogen-progestogen for 10 years, there will be 48 cases per 1000 users (i.e., 21 additional cases).

• Examine your breasts regularly. See your doctor if you notice any changes, such as:
• furrows or creases in the skin;
• changes in the nipples;
• any lump that you can see or feel.

Additionally, it is recommended that you participate in screening programs using mammography. When undergoing mammography screening, inform the nurse or healthcare professional performing the X-rays that you are using HRT, as this medication may increase the density of your breasts, which may affect the results of the mammography. When the breast density increases, the mammography may not detect all lumps.

Ovarian Cancer

Ovarian cancer occurs less frequently than breast cancer. The use of HRT with estrogen-only products or with a combination of estrogen-progestogen has been associated with a slightly higher risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women aged 50-54 years who are not taking HRT, approximately 2 cases of ovarian cancer per 2000 women can be expected over a 5-year period. In women being treated with HRT for 5 years, approximately 3 cases per 2000 patients (i.e., approximately 1 additional case) can be expected.

Effect of HRT on the Heart and Circulation

Blood Clots in a Vein (Thrombosis)

The risk ofblood clots in veinsis approximately 1.3 to 3 times higher for HRT users than for non-users, 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, difficulty breathing, fainting, or even death.

You are more likely to develop a blood clot in your veins with age and if you experience any of the following situations. Inform your doctor if any of the following situations occur to you:

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

For signs of a blood clot, see “Stop using Estradot and see a doctor immediately”.

Comparison

In women in their 50s who are not taking HRT, a mean of 4 to 7 out of 1000 are expected to have a blood clot in a vein over a 5-year period.

In women in their 50s who are taking HRT with a combination of estrogen-progestogen for 5 years, there will be 9 to 12 cases per 1000 users (i.e., 5 additional cases).

In women who have had their uterus removed and are being treated with HRT with estrogen-only products for 5 years, there will be 5 to 8 cases per 1000 users (i.e., 1 additional case).

Heart Disease (Heart Attack)

There is no evidence that HRT prevents heart disease.

Women over 60 years old who are taking HRT with a combination of estrogen-progestogen have a slightly higher risk of developing heart disease than non-users.

In women who have had their uterus removed and are being treated with HRT with estrogen-only products, there is no increase in the risk of developing heart disease.

Stroke

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

Comparison

In women in their 50s who are not taking HRT, a mean of 8 out of 1000 are expected to have a stroke over a 5-year period. In women in their 50s who are being treated with HRT, 11 out of 1000 are expected to have a stroke over a 5-year period (i.e., 3 additional cases).

Other Conditions

• HRT does not prevent memory loss. There is some evidence of a higher risk of memory loss in women who start HRT after the age of 65. Consult your doctor for advice.

Other Medications and Estradot

Some medications may interfere with the effect of Estradot. This may cause irregular bleeding. This occurs with 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, nelfinavir);

-Preparations based on medicinal plants containingSt. John's Wort(Hypericum perforatum);

HRT may affect the functioning of other medications:

• A medication forepilepsy (lamotrigine), as it may increase the frequency of seizures.

-Otherantibiotics(such as ketoconazole, erythromycin).

-Medications for hepatitis C virus (HCV) (e.g., combination regimen for HCV ombitasvir/paritaprevir/ritonavir with or without dasabuvir or glecaprevir/pibrentasvir) may cause elevations in liver function test results (increased ALT levels) in women using HCV with ethinyl estradiol. Estradot contains estradiol instead of ethinyl estradiol. It is unknown whether an increase in ALT levels can occur when Estradot is used with this HCV combination regimen.

Please inform your doctor or pharmacist if you are taking or have recently taken other medications, including those purchased without a prescription, medicinal plants, or other natural products. Your doctor will advise you accordingly.

Laboratory Tests

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

Pregnancy and Breastfeeding

Estradot is a medication only for postmenopausal women. If you become pregnant, stop treatment with Estradot and contact your doctor.

Do not useEstradotif you are pregnant or breastfeeding.

Driving and Operating Machinery

Estradot has no known effects on the ability to drive or operate machinery.

Follow exactly the administration instructions of this medication as indicated by your doctor. Consult your doctor or pharmacist if you have any doubts.

Your doctor will try to prescribe the lowest dose to treat your symptom for the shortest period of time possible. Talk to your doctor if you consider this dose too strong or insufficient.

For how long should you use Estradot

It is essential to use the lowest effective dose and only as long as necessary.

You should periodically discuss with your doctor the possible risks and benefits associated with the use of Estradot and if you still need this treatment.

When to start treatment

-If you are not currently using any hormone replacement therapy (patches or tablets), orif you have been using a continuous combined hormone replacement therapy product (in which estrogen and progestogen are administered every day without interruption), you can start using Estradot on any day.

-If you are changing from a cyclic or sequential hormone replacement therapy (in which progestogen is added for 12-14 days of the cycle), you must start using Estradot the day after completing your previous regimen.

When to apply Estradot

-Each Estradot patch must be changed twice a week (every3 to4 days). It is best to change it always on the same two days of the week (for example, Monday and Thursday). The Estradot package contains a calendar-control on the back that will help you remember your schedule. Mark the two-day schedule you want to follow. Change the patch always on the two days of the week that you have marked.

-You should wear the Estradot patch continuously until you change it for a new patch.

Any adhesive that remains on the skin can be easily removed by friction. If this occurs, place a new Estradot patch on a different area of the skin.

Women who have had a hysterectomy

The Estradot patch must be applied continuously without interruption. It is not necessary to add another type of hormone called progestogen, unless there is growth of the endometrium outside the uterus (endometriosis). Check the risks to consider with hormone replacement therapy in section 2, Warnings and precautions.

Women who still have a uterus

Your doctor will prescribe another hormone for you to take with Estradot, called progesterone, to reduce the risk of uterine cancer. If you apply Estradot continuously without interruption, the progesterone tablet should be taken for at least 12-14 days every month/cycle of 28 days. Check the risks to consider with hormone replacement therapy in section 2, Warnings and precautions.

You may experience irregular bleeding or spotting during the first few months of treatment. If you have heavy bleeding or bleeding or spotting continues after a few months of treatment, talk to your doctor to reevaluate your treatment if necessary (see section 2, Unexpected bleeding).

Where to apply Estradot

Apply the patch to the lower abdomen, below the waist. Avoid the waist, as clothing may cause the patch to peel off. Do not apply the patch to the breasts or near the breasts.

When changing the patch, according to your two-day schedule, apply the new patch to a different area. Do not apply a new patch to the same area for at least a week.

Before applying Estradot, make sure your skin is:

-clean, dry, and fresh,

-free of any powder, oil, cream, or lotion,

-free of cuts and/or irritations.

How to apply Estradot

When changing the patch, peel it off, and fold it in half with the sticky side inwards,See section 5, "Storage of Estradot" for instructions on how to safely dispose of the patch. Do not throw away used patches in the toilet.

Additional practical information

If the patch has been applied correctly, it should not affect you during a bath, swimming, shower, or exercise. If a patch peels off, for example, during a bath or shower, move it to eliminate the water. After drying and allowing the skin to cool, you can apply the same patch to a different area of the skin on the lower abdomen (see "Where to apply Estradot").

If the patch does not adhere completely to the skin, use a new patch. It does not matter what day it occurs, change this patch on the same day according to the initial schedule.

When taking the sun or using a solarium, you should cover the patch. When bathing, you can wear the patch under your swimsuit.

If you need surgery

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

If you use moreEstradotthan you should

If you have taken too muchEstradot, remove the patch. The symptoms of overdose are usually breast pain and/or vaginal bleeding.It is unlikely to have an acute overdose due to the administration route ofEstradot(the patch releases the drug gradually). If symptoms persist, contact your doctor.

If you forget to useEstradot

If you forget to change the patch, apply another patch as soon as you remember. It does not matter what day this occurs, change the patch on the same days as in the initial schedule.

Do not take a double dose to compensate for the missed application.

If you interrupt treatment withEstradot

Stopping treatment withEstradotmay increase the risk of irregular bleeding or spotting. Inform your doctor if this occurs. After a prolonged period without treatment, you should consult your doctor before starting to use the patch again.

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

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

The following diseases are observed more frequently in women treated with THS compared to women not treated with THS:

• breast cancer;
• abnormal growth of the inner wall of the uterus (endometrial hyperplasia) or cancer of the inner wall of the uterus (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 at 65 years of age or older.

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

Some side effects can be serious

The following symptoms require immediate medical attention:

• Sudden chest pain;
• Chest pain that spreads to the arm or neck;
• Difficulty breathing;
• Painful and swollen legs;
• Yellowing of the eyes and face, darkening of the urine, itching (jaundice);
• Unexpected bleeding or spotting after using Estradot for some time or if this continues after stopping treatment;
• Changes in the breasts, such as skin changes, changes in the nipples, lumps that can be seen or felt (breast cancer);
• Heavy menstrual periods;
• Unexplained migraines.

Stop treatment with Estradotandcontact your doctorimmediately if you experience any of the side effects mentioned above.

Check the risks to consider with hormone replacement therapy in section 2, Adverse Reactions and Precautions.Adverse Reactions and Precautions.

Other side effects

Estradot may also cause the following side effects.If you consider that any of the side effects you experience are serious, inform your doctor or pharmacist.

Very common side effects,can affectmore than 1 in 10 people:

Headache, skin reactions at the patch application site (including irritation, burning, rash, dryness, bleeding, bruising, inflammation, swelling, skin discoloration, urticaria, and blisters), breast tenderness and pain, menstrual cramps, menstrual irregularities.

Common side effects,can affect up to 1 in 10 people:

Depression, nervousness, mood changes, insomnia, nausea, bad digestion, diarrhea, abdominal pain, feeling bloated, acne, rash, dry skin, itching, breast growth, heavy menstrual periods, white or yellowish discharge from the vagina, irregular bleeding, severe uterine contractions, vaginal inflammation, abnormal growth of the uterus (endometrial hyperplasia), pain (e.g. back pain, arm pain, leg pain, wrist pain, ankle pain), weakness, swelling in the extremities (arms and legs), weight changes.

Uncommon side effects,can affect up to 1 in 100 people:

Migraine, dizziness, increased blood pressure, vomiting, skin discoloration, liver function abnormalities.

Rare side effects,can affect up to 1 in 1000 people:

Tickling or numbness in the hands and feet, blood clots, gallstones, hair loss, muscle weakness, benign growth of the uterus, cysts near the fallopian tubes, polyps (small growths) on the cervix of the uterus (cervical polyps), changes in sexual desire, allergic reactions such as rashes.

Very rare side effects,can affect up to 1 in 10,000 people:

Urticaria, severe allergic reactions (including difficulty breathing; swelling of the face, tongue, throat, or skin; dizziness and urticaria), decreased tolerance to carbohydrates, involuntary movements that can affect the eyes, head, and neck, discomfort with contact lenses, severe skin reactions, excessive hair growth.

Side effects of unknown frequency(cannot be estimated with available data):

Breast cancer, abnormal liver function tests, allergic inflammation of the skin, non-cancerous lumps in the breast.

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

• Gallbladder disease;
• Various skin changes:

• Discoloration of the skin, especially on the face or neck, known as "pregnancy spots" (melasma);
• Painful and red nodules on the skin (erythema nodosum);
• Rash with redness in the shape of a target or sores (erythema multiforme);

• Decreased memory or mental capacity (possible dementia)

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, 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 Vigilance of Medicinal Products for Human Use (https://www.notificaram.es). By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• Store Estradot in the original package, in a cool and dry place. Once opened or the protective liner removed, apply the patch to the skin immediately.
• Do not refrigerate or freeze Estradot.
• Do not use this medicationafter the expiration date that appears on the package after CAD/EXP. The expiration date is the last day of the month indicated.
• Do not use this medication if you observe that the container is damaged or shows signs of manipulation.
• After removing the patch, fold it in half with the adhesive side in and keep it in a safe place out of the reach of children.Used or unused transdermal patches must be disposed of according to local regulations or returned to the pharmacy, preferably in the original packaging.
• Medications should not be thrown away through drains or in the trash. Deposit the containers and medications you no longer need at the SIGRE point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medications you no longer need. In this way, you will help protect the environment

Composition of Estradot

Each 25 micrograms/24 hours transdermal patch contains 0.39 mg of estradiol (as hemihydrate) and releases 25 micrograms of estradiol every 24 hours.

• The active ingredient is estradiol (as hemihydrate).
• The other components of the adhesive film of the patch are: acrylic adhesive, adhesive silicone, oleic alcohol, dipropylene glycol, povidone (E1201).
• The support layer is an ethylene/vinyl acetate copolymer and a laminated copolymer of vinylidene chloride/methacrylate.
• The protective layer (which is removed before applying the patch) is a polyester film coated with fluoropolymer.

Appearance of the product and contents of the package

Estradot 25 is a rectangular patch of 2.5 cm x 2 cm with rounded edges, composed of a pressure-sensitive adhesive layer containing estradiol, a translucent support layer on one side, and a protective layer on the other.

Estradot is available in four different concentrations: 25, 37.5, 50, and 75 micrograms/24 hours. Not all concentrations may be available.

Estradot is available in packages of 2, 8, 24, and 26 patches. Not all formats may be available.

Marketing Authorization Holder

BEXAL FARMACÉUTICA, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Responsible for manufacturing

Novartis Farmacéutica, S.A.

Gran Vía de les Corts Catalanes, 764

08013 Barcelona

Spain

Novartis Pharma GmbH

Roonstrasse 25

D-90429 Nürnberg

Germany

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Austria: Estradot

Denmark: Vivelle dot

Finland: Estradot

France: Vivelledot

Croatia: Estradot

Island: Vivelle dot

Ireland: Estradot

Norway: Estradot

Portugal: Estradot

Spain: Estradot

Sweden: Estradot

United Kingdom (Northern Ireland): Estradot

Last review date of this leaflet:July 2024

Other sources of information

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