Evopad 25 micrograms/24 H transdermal patches

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Evopad 25 µg/24 h transdermal patches

Estradiol

Read the entire leaflet carefully before you start using this medicine because 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 only. Do not give it to other people, even if they have the same symptoms as you, because it could harm them.

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

Contents of the leaflet:

1. What Evopad 25 µg/24 h transdermal patches are and what they are used for
2. What you need to know before using Evopad 25 µg/24 h transdermal patches
3. How to use Evopad 25 µg/24 h transdermal patches
4. Possible side effects
5. How to store Evopad 25 µg/24 h transdermal patches
6. Contents of the pack and other information

1. What Evopad 25 (g/24 h transdermal patches) is and what it is used for

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

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

• Treatment of menopausal symptoms, whether 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 and does not restore fertility.

2. What you need to know before using Evopad 25 (g/24 h transdermal patches)

Follow carefully 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 components 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 pregnant
• You have undiagnosed abnormal 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 loose and affects the lung)
• You have a blood clotting disorder (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 a severe liver disorder, until liver function has returned to normal
• You have porphyria (a disorder of a blood pigment).

Warnings and precautions

Talk to 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 treatment adjustment or continuation is needed.

For the treatment of menopausal symptoms, hormone replacement therapy (HRT) should only be initiated when symptoms affect a 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 while benefits outweigh risks. The lowest effective dose and the shortest possible duration of treatment should always be considered.

Evidence regarding risks associated with HRT used for 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 during treatment you experience repeated sudden bleeding, unexpected vaginal bleeding, or detect changes during breast examination, 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 disorder 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:

• Disorders or impairments 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 occur, 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, difficulty swallowing, or hives accompanied by breathing difficulties, suggesting angioedema

Take special care not to exceed the recommended doses.

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

Evopad does not help improve memory.

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

THROMBOSIS (blood clots)

Hormone replacement therapy increases the risk of thrombosis (blood clots), and this risk is highest 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 radiating to 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 temporarily increase if you need to remain immobile 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 bedridden for some time, inform your doctor.

Breast cancer

Available data show that the use of hormone replacement therapy (HRT), either combined estrogen-progestogen or estrogen-only, increases the risk of breast cancer. The additional risk depends on how long you use HRT. The increased risk becomes evident after 3 years of use. After stopping HRT, the additional risk gradually decreases over time, but the risk may persist for 10 years or more if you have used HRT for longer 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 will be diagnosed per 1000 women over a 5-year period.

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

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

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

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

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

Ovarian cancer

Ovarian cancer is less common than breast cancer. The use of HRT, whether with estrogen alone or combined estrogen-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 not using HRT, about 2 cases of ovarian cancer are observed per 2000 women over a 5-year period. In women undergoing HRT for 5 years, about 3 cases are observed per 2000 women (i.e., about 1 additional case).

In addition, when estrogens are administered over long periods, the risk of developing tumors and abnormalities in the uterus increases. See section 4. Possible Adverse Effects. For estrogen-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 cycle, 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 the 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, have recently taken, or might take 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 stopping them.

HRT may affect how other medicines work:

a medicine for epilepsy (lamotrigine), as it may increase the frequency of seizures.

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

Do not use this medicine if you are breastfeeding.

Driving and operating machinery

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

3. How to use Evopad 25 (g/24 h transdermal patches

Follow exactly the dosing instructions given by your doctor. 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.

The Evopad patch should be applied twice a week, removing each used patch after 3–4 days.

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

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

Combined treatment with a 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 for 12 or 14 consecutive days per 28-day cycle/month is recommended.

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

Instructions for correct application

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

Each new application should be made on a slightly different skin area of 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 skin area where the patch will be placed.

Removing the patch

• Gently peel off one edge of the patch 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 therefore treatment should be symptomatic. These symptoms may resolve if 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 forgotten doses.

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. Maintain your regular patch-change day. 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 experiences them.

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

Adverse reactions are listed below, classified by frequency according to 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

In clinical trials with EVOPAD 25 µg/24 h transdermal patches, the following side effects have been reported:

• 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, diarrhea
  ? Uncommon: flatulence, difficult and laborious digestion
  ? Rare: abdominal distension, vomiting, gas (flatulence)

• Hepatobiliary disorders
  ? Rare: gallstones

• Skin and subcutaneous tissue disorders
  ? Common: itching, rash, dry skin
  ? Uncommon: skin discoloration, urticaria, redness of the skin 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
  ? 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: swelling due to fluid accumulation in tissues, swelling due to fluid accumulation in various body parts, swelling due to fluid accumulation in legs and feet (edema)
  ? Rare: fatigue

• Additional investigations
  ? Common: weight gain

• Laboratory abnormalities
  ? Uncommon: increased transaminases (laboratory test indicative of 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 the 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 estrogen 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 the 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 starting from age 60.

Risk of stroke:

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

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

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

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

Reporting of adverse effects:

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through 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 25 (g/24 h transdermal patches

Keep out of the sight and reach of children.

Do not store above 25 ºC.

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

Medicines must not be disposed of via wastewater or household waste. Dispose of unused containers and medicines at the SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of unused containers and medicines. This way, you will help protect the environment.

6. Contents of the pack and other information

Composition of EVOPAD 25?g/24 h transdermal patches

• The active substance is estradiol. Each transdermal patch contains 1.60 milligrams of estradiol hemihydrate, corresponding to a release of 25 micrograms of estradiol per 24 hours.
• The other components are: Acrylate-vinyl acetate copolymer adhesive, guar gum, polyester film.

Appearance of the product and contents of the pack

The product is presented in boxes containing 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 PRESENTATIONS:

EVOPAD 50?g/24 h transdermal patches: Pack containing 8 patches.
EVOPAD 75?g/24 h transdermal patches: Pack containing 8 patches.
EVOPAD 100?g/24 h transdermal patches: Pack containing 8 patches.

This patient information 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/