Evopad 50 micrograms/24 H transdermal patches

Patient Information Leaflet

Introduction

Patient Information Leaflet

Evopad 50?g/24 h Transdermal Patches

Estradiol

Read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

? Keep this leaflet, as you may need to read it again.

? If you have any questions, ask your doctor or pharmacist.

? This medicine has been prescribed for you; do not give it to other people, even if they have the same symptoms as you, as it may harm them.

? If you experience any adverse effects, consult your doctor or pharmacist, even if they are effects not listed in this leaflet (see section 4).

Leaflet Contents:

1. What Evopad 50?g/24 h transdermal patches are and what they are used for
2. What you need to know before using Evopad 50?g/24 h transdermal patches
3. How to use Evopad 50?g/24 h transdermal patches
4. Possible side effects
5. How to store Evopad 50?g/24 h transdermal patches
6. Contents of the pack and other information

1. What Evopad 50(g/24 h transdermal patches are and what they are used for

Evopad transdermal patches of the matrix type belong to the pharmacotherapeutic group G03CA03 (oestrogens).

Evopad transdermal patches are indicated as hormone replacement therapy (HRT) for:

• Treatment of menopausal symptoms, natural or surgically induced, e.g. hot flushes, night sweats, urogenital disorders (atrophic vaginitis)

• Prevention of osteoporosis (loss of bone mass) if you are at high risk of future fractures and cannot use other medications for this purpose. Please consult your doctor about all available treatment options.

This medicine must not be used to prevent heart disease or to enhance intellectual capacity.

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

2. What you need to know before using Evopad 50 (g/24 h transdermal patches

Carefully follow all instructions given by your doctor.

Read the following information before using this medicine.

Do not use Evopad transdermal patches if:

• You are allergic (hypersensitive) to estradiol or to any of the other ingredients of this medicine (listed in section 6)
• You have or have had breast or uterine cancer, or suspect you may have it
• You are pregnant or suspect you might be
• You have undiagnosed genital bleeding
• You have or have had endometrial cancer or endometrial hyperplasia (abnormal growth of the endometrium)
• You have or have had venous thrombosis (blood clots in the leg veins) or pulmonary embolism (a blood clot in the leg veins that breaks off and affects the lung)
• You have a condition affecting blood clotting (thrombophilia), for example, protein C deficiency, protein S deficiency, or a substance called antithrombin (see section "Take special care with Evopad transdermal patches")
• You have or have recently had arterial thrombosis (e.g., angina pectoris, myocardial infarction, stroke, retinal artery involvement)
• You have or have had severe liver disease, until liver function has returned to normal
• You have porphyria (a disorder of a blood pigment).

Warnings and precautions

Consult your doctor or pharmacist before starting to use this medicine.

Visit your doctor regularly and at least once a year. Discuss with your doctor at each visit whether the treatment should be adjusted or continued.

For the treatment of menopausal symptoms, hormone replacement therapy (HRT) should only be initiated when symptoms affect the woman's quality of life. In all cases, a careful assessment of risks and benefits should be performed at least annually, and HRT should only be continued as long as benefits outweigh risks. The lowest effective dose and shortest possible duration of treatment should always be considered.

Evidence regarding risks associated with HRT for the treatment of premature menopause is limited. However, HRT use may be more favorable in younger women than in older women due to the lower risk level in this patient group.

Medical examination and follow-up:

Before starting hormone replacement therapy (HRT), you must 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 thereafter.

If you experience repeated sudden bleeding, unexpected vaginal bleeding, or detect changes during breast examination while on treatment, a new medical evaluation will be necessary.

Certain conditions require monitoring by your doctor.

You should consult your doctor if any of the following conditions occur or have occurred previously and/or worsened during pregnancy or during previous hormonal treatment:

• Gynecological disorders of any type
• History or risk factors for developing blood clots (thrombosis)
• Risk factors for breast cancer
• High blood pressure, particularly if it worsens or does not improve with antihypertensive treatment
• Liver disorders
• Diabetes
• Disorders affecting gallbladder function
• Severe and recurrent migraines
• An immune disease called systemic lupus erythematosus
• Epilepsy
• Asthma
• Hearing problems
• Severe swelling of the skin and other tissues of hereditary type
• Changes or abnormalities in the breasts
• Pregnancy
• Pruritus (itching)
• Hereditary and acquired angioedema

During treatment with this medicine, your doctor will monitor you continuously if you have any of the following conditions:

• Impairment in heart or kidney function. Estrogens may cause fluid retention.
• Mild disorders or deficiencies in liver function
• History of jaundice (yellowing of the whites of the eyes and skin)
• High levels of fat (triglycerides) in the blood or a family history of this condition

You must discontinue treatment if any of the conditions listed in the section Do not use Evopad transdermal patches apply, or if you experience any of the following:

• Jaundice (yellowing of the whites of the eyes and skin) or worsening of liver function
• Marked increase in blood pressure
• New episodes of migraine-type headache
• Pregnancy
• Swelling of the face, tongue, or throat and difficulty swallowing, or hives accompanied by difficulty breathing, suggesting angioedema

Take special care not to exceed the recommended doses.

Some patients may develop skin pigmentation spots, especially those who previously had such spots during pregnancy. In these cases, minimizing exposure to sunlight and/or ultraviolet radiation is recommended while using this medicine.

Evopad does not help improve memory.

During treatment with hormone replacement therapy, certain serious conditions such as blood clots (thrombosis) and some types of tumours may occur more frequently.

THROMBOSIS (blood clots)

Hormone replacement therapy increases the risk of thrombosis (blood clots), and this risk is higher 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 may break loose and block the pulmonary arteries (pulmonary embolism). Blood clots may also occur, although much less frequently, in the arteries of the heart (myocardial infarction, angina pectoris), in the cerebral arteries (cerebral thrombosis), or in the eyes (loss of vision or double vision).

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

• Pain and swelling in one leg
• Sudden onset of coughing
• Severe chest pain, sometimes also in the arm
• Difficulty breathing
• Severe and unusual headache
• Vision problems (loss of vision, double vision)
• Difficulty speaking clearly
• Dizziness
• Seizures
• Weakness or numbness affecting one side of the body
• Difficulty walking or holding objects

The risk of blood clots may increase temporarily if you are immobilized for a period due to surgery or another reason. Therefore, in such cases, you should consult your doctor, as it may be advisable to interrupt your treatment until you have fully regained mobility. If you are scheduled for surgery and know in advance that you will be confined to bed for a period, inform your doctor.

Breast cancer

Available data show that the use of hormone replacement therapy (HRT) with combined oestrogen-progestogen or with oestrogen alone increases the risk of breast cancer. The additional risk depends on how long you use HRT. The additional risk becomes evident 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 to 54 years who are not using HRT, an average of 13 to 17 cases of breast cancer per 1000 women will be diagnosed over a 5-year period.

In women aged 50 who start oestrogen-only hormone replacement therapy for 5 years, there will be 16 to 17 cases per 1000 women users (i.e., 0 to 3 additional cases).

In women aged 50 who start combined oestrogen-progestogen HRT for 5 years, there will be 21 cases per 1000 women users (i.e., 4–8 additional cases).

In women aged 50 to 59 who are not taking HRT, an average of 27 cases of breast cancer per 1000 women will be diagnosed over a 10-year period.

In women aged 50 who start oestrogen-only HRT for more than 10 years, there will be 34 cases per 1000 women users (i.e., seven additional cases).

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

Ovarian cancer

Ovarian cancer occurs less frequently than breast cancer. The use of HRT with oestrogen alone or with combined oestrogen-progestogen 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 years who are not using HRT, about 2 cases of ovarian cancer per 2000 women have been observed over a 5-year period. In women receiving HRT for 5 years, about 3 cases per 2000 patients have been observed (i.e., about 1 additional case).

Also, when oestrogens are administered for long periods, the risk of developing tumours and abnormalities in the uterus increases. See section 4. Possible Adverse Effects. For oestrogen-containing products: If you still have your uterus, your doctor will prescribe another hormone, progesterone, to reduce the risk of uterine cancer. At the end of the progesterone treatment period, bleeding may occur. Inform your doctor if you experience heavy or irregular bleeding during the cycle.

You should discuss with your doctor the possible alternative treatments available for your specific condition and how long treatment should last. This should be reviewed periodically throughout the course of treatment.

Inform your doctor that you are using Evopad transdermal patches, as they may alter the results of certain laboratory tests or analyses.

This medicine 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 function and may even worsen it if you are over 65 years of age.

Children and adolescents

Evopad transdermal patches must not be used in children.

Use of other medicines

Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those obtained without a prescription. Your doctor will advise you accordingly.

It is especially important that you inform your doctor if you are taking or plan to take any of the following medicines, as they may interact with this medicine and alter its effect: antiepileptic medicines (e.g. phenobarbital, phenytoin and carbamazepine), a medicine for high blood pressure (bosentan), antibiotics and other anti-infective medicines (e.g. rifampicin, rifabutin, erythromycin, ketoconazole, nevirapine, efavirenz, ritonavir, nelfinavir), certain antiulcer medicines (cimetidine), and herbal preparations containing St. John's wort – Hypericum perforatum. The effect of these herbal preparations may persist for up to two weeks after discontinuation.

HRT may affect how other medicines work:

an antiepileptic medicine (lamotrigine), as it may increase the frequency of seizures.

Medicines for hepatitis C virus (HCV) (e.g., HCV combination regimens ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirine; glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir) may cause increases in blood liver function tests (elevation of liver enzyme ALT) in women using HRT containing ethinylestradiol. Evopad contains estradiol instead of ethinylestradiol. It is unknown whether an increase in liver enzyme ALT may occur when Evopad is used with these HCV combination regimens.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Do not use this medicine if you are pregnant or planning to become pregnant.

Do not use this medicine if you are breastfeeding.

Driving and use of machines

Adverse effects of this medicinal product on the ability to drive or operate machinery have not been reported.

3. How to use Evopad 50(μg/24 h) transdermal patches

Follow exactly the instructions given by your doctor for using this medicine. If in doubt, consult your doctor or pharmacist.

Remember to use your medicine.

Do not stop treatment before your doctor tells you to do so, as menopausal symptoms may return.

If you think that the effect of this medicine is too strong or too weak, inform your doctor or pharmacist.

Evopad patches should be applied twice a week, replacing each used patch after 3-4 days.

Your doctor will determine the duration of your treatment with Evopad.

• Cyclic treatment: 3 weeks of treatment followed by a 7-day therapeutic break, during which vaginal bleeding may occur.
• Continuous treatment: For women without a uterus or in cases of severe estrogen deficiency symptoms during the therapeutic break.

Combined treatment with progestogen:

• In 21-day cyclic regimens with estradiol, concomitant administration of a progestogen is recommended during the last 12 or 14 days of the cycle (e.g., starting on day 8 or 10 of the cycle).
• In continuous estradiol regimens, concomitant administration of a progestogen is recommended for 12 or 14 consecutive days per month/cycle of 28 days.

In both treatment regimens, vaginal bleeding may occur after discontinuation of the progestogen.

Instructions for correct application

Open the pouches and remove the two parts of the protective liner by the "S"-shaped slit. The adhesive side of the transdermal system must be immediately applied to clean, dry, intact, and healthy skin, pressing gently with the fingers during application. Warm and press the patch onto the skin with the palm of your hand for at least 10 seconds. The pressure and warmth from your hand are essential to ensure maximum adhesion of the patch.

Each application should be made on a slightly different area of skin on the trunk, below the waist.

The patch may remain in place during bathing and showering. If it detaches and cannot be properly reattached, a new patch should be applied immediately.

Do not apply the patch on or near the breasts.

Do not apply creams, lotions, or powders to the area of skin where the patch will be applied.

Patch removal

• Gently peel one edge of the patch away from the skin.
• Fold the patch in half so that the adhesive side sticks to itself.
• Store it in a safe place, out of reach of children and pets.
• Do not flush used patches down the toilet (see section 5. Storage of Evopad transdermal patches).

After removing the patch, some adhesive residue may remain on the skin. This will disappear over time, or you may use baby oil to remove it.

If you use more Evopad transdermal patches than you should

If you have used more of this medicine than you should, inform your doctor or pharmacist.

It is unlikely that you will use more Evopad than recommended with this type of application. Symptoms of overdose may include breast tenderness or pain, and spotting. Some women may also experience nausea, vomiting, and cessation of bleeding. There is no specific antidote, and treatment would therefore be symptomatic. These symptoms may resolve once the patch is removed.

In case of overdose or accidental ingestion, contact the toxicology information service. Telephone: (91) 562 04 20.

If you forget to use Evopad transdermal patches

Do not take a double dose to make up for a missed dose.

If you forgot to change the patch on the scheduled day, do not worry—change it as soon as possible. Resume treatment according to the originally planned cycle. The usual patch-change day remains unchanged. Missing a dose may increase the likelihood of breakthrough bleeding or spotting during the cycle. If you have any doubts, consult your doctor or pharmacist.

4. Possible adverse effects

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

If you consider any of the adverse effects you experience to be severe, or if you notice any adverse effect not mentioned in this leaflet, inform your doctor or pharmacist.

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

Very common: may affect more than 1 in 10 people
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
Not known

The following side effects have been reported in clinical trials of EVOPAD 50?g/24 h transdermal patches:

• Infections and infestations
  ? Common: genital candidiasis (genital infection)
  ? Uncommon: genital candidiasis

• Benign, malignant and unspecified neoplasms (incl. cysts and polyps)
  ? Rare: breast cancer
  ? Not known: endometrial cancer

• Immune system disorders
  ? Uncommon: allergic reaction

• Metabolism and nutrition disorders
  ? Common: weight gain or weight loss

• Psychiatric disorders
  ? Uncommon: depression
  ? Rare: anxiety, increased or decreased libido (sexual desire)

• Nervous system disorders
  ? Common: headache, nervousness, mood changes, insomnia
  ? Uncommon: dizziness, vertigo
  ? Rare: paresthesia (tingling sensation), epilepsy, migraine (severe headache)
  ? Not known: stroke

• Eye disorders
  ? Uncommon: visual disturbance
  ? Rare: intolerance to contact lenses

• Cardiac disorders
  ? Uncommon: palpitations
  ? Not known: myocardial infarction

• Vascular disorders
  ? Uncommon: increased blood pressure
  ? Rare: thrombosis (blood clots)
  ? Not known: deep vein thrombosis (blood clots in the veins)

• Respiratory, thoracic and mediastinal disorders
  ? Not known: pulmonary embolism (blood clots in the lungs)

• Gastrointestinal disorders
  ? Common: nausea, abdominal pain, diarrhoea
  ? Uncommon: flatulence, dyspepsia
  ? Rare: abdominal distension, vomiting, gas (flatulence)

• Hepatobiliary disorders
  ? Rare: gallstones

• Skin and subcutaneous tissue disorders
  ? Common: itching, rash, dry skin
  ? Uncommon: skin discoloration, urticaria, skin redness accompanied by pain
  ? Rare: excessive hair growth in women (hirsutism), acne
  ? Not known: severe swelling of the skin and other tissues (especially lips or eyes)

• Musculoskeletal and connective tissue disorders
  ? Common: joint pain, back pain
  ? Uncommon: muscle pain
  ? Rare: muscle weakness (myasthenia), muscle cramps

• Reproductive system and breast disorders
  ? Very common: menstrual cycle disturbances
  ? Common: irregular or continuous uterine bleeding, abnormally heavy and prolonged menstrual periods, irregular vaginal bleeding, uterine cramps, vaginal inflammation, thickening of the uterine wall, vaginal/uterine bleeding including spotting
  ? Uncommon: breast enlargement, painful menstruation, breast pain, breast tenderness on palpation
  ? Rare: benign uterine tumor (uterine fibroid), breast lumps, cervical polyps (polyps near the cervix), painful menstruation, premenstrual syndrome, breast enlargement, white discharge

• General disorders and administration site conditions
  ? Very common: itching at application site, rash at application site
  ? Common: pain, weakness, edema at application site, redness at application site, reaction at application site, weight changes
  ? Uncommon: fluid retention, swelling due to fluid accumulation in various parts of the body, swelling of legs and feet due to fluid accumulation (edema)
  ? Rare: fatigue

• Complementary investigations
  ? Common: weight gain

• Laboratory abnormalities
  ? Uncommon: increased transaminases (laboratory test indicating liver function)

Risk of tumor development:

HRT increases the risk of breast cancer. The risk is higher in women who use estrogens combined with progestogens. The risk of breast cancer increases with longer duration of treatment.

Estrogen-only therapy is not recommended in women with an intact uterus. If you still have your uterus, your doctor will prescribe another hormone, progesterone, for 12 days each cycle to reduce the risk of uterine cancer.

Long-term treatment with estrogens alone or in combination has been associated with an increased risk of ovarian tumors.

Risk of thrombosis:

Hormone replacement therapy increases the risk of thrombosis (blood clots), with this risk being higher during the first year of use.

Risk of heart artery disease:

The risk of developing heart artery disease may increase in women using combined therapy from the age of 60 onwards.

Risk of stroke:

The use of HRT is associated with an increased risk of stroke.

The following side effects have been reported with oral treatment using synthetic estrogens alone or combined with progestogens: benign or malignant estrogen-dependent neoplasms (e.g. endometrial cancer), myocardial infarction, stroke, gallbladder disorders, skin and subcutaneous tissue disorders (chloasma, erythema multiforme, erythema nodosum, vasculitic purpura, skin inflammation (contact dermatitis), generalized itching sensation (generalized pruritus), urticaria and angioedema (deep skin swelling), probable dementia.

If any other adverse reaction not described above occurs, consult your doctor or pharmacist.

If any of these effects occur, stop treatment and consult your doctor.

Reporting of adverse effects:

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Evopad 50 (50 g/24 h transdermal patches)

Keep out of the sight and reach of children.

Do not store above 25 °C.

Do not use Evopad transdermal patches after the expiry date stated on the packaging.

Medicines must not be disposed of via wastewater drains or household waste. Unused medicines and their packaging should be returned to the pharmacy's SIGRE collection point . If you are unsure, please ask your pharmacist how to properly dispose of unused medicines and their packaging. This helps protect the environment.

6. Package contents and other information

Composition of EVOPAD 50?g/24 h transdermal patches

• The active substance is estradiol. Each transdermal patch contains 3.2 milligrams of estradiol hemihydrate, which corresponds to a release of 50 micrograms of estradiol every 24 hours.
• The other components are: Acrylate-vinyl acetate copolymer adhesive, Guar gum, Polyester film.

Presentation of the product and contents of the pack

The product is presented in packs of eight square, transparent, self-adhesive transdermal patches, 0.2 millimetres thick, for application to the skin surface.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder: Theramex Ireland Limited
3rd Floor, Kilmore House,
Park Lane, Spencer Dock,
Dublin 1
D01 YE64
Ireland

Manufacturer: Aesica Pharmaceuticals GmbH
Alfred-Nobel-Str. 10
40789 Monheim am Rhein
Germany

Local representative of the Marketing Authorization Holder:
Theramex Healthcare Spain, S.L.
Calle Martínez Villergas 52, Edificio C, planta 2ª izquierda
28027 Madrid
Spain

OTHER PACK SIZES:

EVOPAD 25?g/24 h transdermal patches: Pack of 8 patches.
EVOPAD 75?g/24 h transdermal patches: Pack of 8 patches.
EVOPAD 100?g/24 h transdermal patches: Pack of 8 patches.

This leaflet was approved in 04/2026

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/