PROSPECTO: INFORMATION FOR THE USER

Evopad 75?g/24 h transdermal patches

Estradiol

1. What is Evopad 75?g/24 h transdermal patches and for what it is used

1. What you need to know before starting to use Evopad 75?g/24 h transdermal patches
2. How to use Evopad 75?g/24 h transdermal patches
3. Possible adverse effects
4. Storage of Evopad 75?g/24 h transdermal patches
5. Contents of the package and additional information

EVOPAD 75?g/24 h transdermal patches of the matrix type belong to the pharmacotherapeutic group G03CA03 (estrogens).

EVOPAD 75?g/24 h transdermal patchesare indicated for hormone replacement therapy (HRT) as:

• Treatment of menopausal symptoms, either natural or surgically induced, e.g. hot flashes, night sweats, urogenital disorders (vulvovaginitis atrophy)

-Prevention of osteoporosis (bone mass loss) if you have a high risk of future fractures and cannot use other medications for this purpose. Consult your doctor about all available treatment options.

EVOPAD 75?g/24 h transdermal patches should not be used to prevent heart disease or to improve cognitive function.

EVOPAD 75?g/24 h transdermal patchesare not a contraceptive, nor do they restore fertility.

Follow carefully all instructions given by your doctor.

Read the following information before using EVOPAD 75?g/24 h transdermal patches.

Do not use EVOPAD 75?g/24 h transdermal patches if:

• You are allergic (hypersensitive) to estradiol or to any of the other components of this medication (including those listed in section 6)
• You have or have had breast cancer or uterine cancer or if you suspect you may have it
• You are pregnant or suspect you may be
• 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 deep vein thrombosis (blood clots in the veins of the legs) or pulmonary embolism (blood clot in the veins of the legs that breaks off and affects the lung)
• You have any condition that affects blood clotting (thrombophilia), for example, deficiency in protein C, protein S, or a substance called antithrombin (see section Be careful with EVOPAD75?g/24 h transdermal patches)
• You have or have had recent arterial thrombosis (e.g. angina, heart attack, stroke, retinal artery damage)
• You have or have had severe liver disease, until it returns to normal
• You have porphyria (a blood pigment disorder).

Warnings and precautions

Consult your doctor or pharmacist before starting to use EVOPAD 75?g/24 h transdermal patches.

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

For the treatment of climacteric symptoms, HRT should only be initiated when symptoms affect the quality of life of the woman. In all cases, a careful assessment of the risks and benefits should be made annually, and HRT 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.

The evidence of the risks associated with HRT as a treatment for premature menopause is limited. However, it may be more favorable to use HRT in young women than in older women due to the low risk in this group of patients.

Medical examination and follow-up:

Before starting 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.

If during treatment, you experience repeated sudden bleeding, unexpected vaginal bleeding, and changes are detected during breast examination, a new medical examination will be necessary.

Some situations will require monitoring by your doctor.

You should see your doctor if you experience any of the following situations or have had them previously and/or worsened during pregnancy or during a previous hormone treatment:

• Any type of gynecological disorder
• History or risk factors for developing thrombi (blood clots)
• Risk factors for breast cancer
• Elevated blood pressure, particularly if it worsens or does not improve with antihypertensive treatment
• Liver disorders
• Diabetes
• Biliary tract disorders
• Severe migraines
• Systemic lupus erythematosus (a type of immune disorder)
• Epilepsy
• Asthma
• Ear problems
• Severe skin swelling of a hereditary type
• Changes or abnormalities in the breasts
• Pregnancy
• Pruritus
• Hereditary and acquired angioedema

During treatment with EVOPAD 75?g/24 h transdermal patches, your doctor will continue to monitor you if you experience any of the following situations:

• Alterations in the functioning of your heart or kidneys. Estrogens cause fluid retention.
• Mild liver function disorders
• History of jaundice (yellowing of the whites of the eyes and skin)
• High levels of fat (triglycerides) in the blood or family history of this

You should discontinue treatment if you meet any of the conditions indicated in the sectionDo not use EVOPAD 75?g/24 h transdermal patchesand experience any of the following situations:

• J jaundice (yellowing of the whites of the eyes and skin) or deterioration in liver function
• Significant increase in blood pressure
• New episodes of migraines
• Pregnancy
• Swelling of the face, tongue, or throat and difficulty swallowing or urticaria accompanied by difficulty breathing, suggesting angioedema

Be careful not to exceed the recommended doses.

Some patients may develop skin patches, especially those who have had them during pregnancy. In these cases, it is recommended to minimize exposure to the sun and/or ultraviolet radiation while using EVOPAD.

EVOPAD does not help improve memory.

During treatment with hormone replacement therapy, some serious diseases may occur more frequently, such as blood clots and certain types of tumors.

BLOOD CLOTS (THROMBOSIS)

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

Blood clots can block major blood vessels. If the blood clot forms in the deep veins of the legs, it can break off and block the pulmonary arteries (pulmonary embolism). Blood clots also occur, although much less frequently, in the coronary arteries (heart attack, angina), cerebral arteries (stroke), or eyes (loss of vision or double vision).

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

• Pain and swelling in a leg
• Sudden cough
• Severe chest pain and sometimes arm pain
• Difficulty breathing
• Severe headache
• Visual problems (loss of vision, double vision)
• Difficulty speaking clearly
• Dizziness
• Convulsions
• Weakness or numbness affecting a part of the body
• Difficulty walking or holding things

The risk of blood clots may increase temporarily if you are immobile for a period of time due to surgery or other reasons. Therefore, you should consult your doctor as it may be necessary to discontinue treatment until you fully recover your mobility. If you are to undergo surgery and know in advance that you will be bedridden for a period of time, inform your doctor.

BREAST CANCER

The available data show that the use of hormone replacement therapy (HRT) with estradiol-progestogen combinations or with estradiol alone 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 HRT has been used for more than 5 years.

Comparison

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

In women aged 50 who initiate HRT with estradiol alone 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 who initiate HRT with estradiol-progestogen for 5 years, there will be between 21 cases per 1000 users (i.e. between 4-8 cases).

In women aged 50-59 who are not taking 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 initiate HRT with estradiol alone for more than 10 years, there will be 34 cases per 1000 users (i.e. 7 additional cases).

In women aged 50 who initiate HRT with estradiol-progestogen 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 estradiol alone or with estradiol-progestogen combinations has been associated with a slightly increased risk of ovarian cancer.

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

Furthermore, when estradiol is administered for long periods of time, the risk of developing tumors and abnormalities in the uterus increases. See section 4. Possible Adverse Effects. For products containing estradiol: If you retain the uterus, your doctor will prescribe another hormone, progesterone, to reduce the risk of uterine cancer. At the end of the treatment period with progesterone, bleeding may occur. Inform your doctor if you experience heavy or irregular bleeding throughout the cycle.

You should discuss with your doctor the possible alternative treatments available for your specific situation and how long the treatment should be prolonged. This should be reviewed periodically throughout treatment.

Inform your doctor that you are taking EVOPAD 75?g/24 h transdermal patches as it may alter the results of certain tests or laboratory analyses.

EVOPAD 75?g/24 h transdermal patches 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 capacity, and may even worsen it if you are over 65 years old.

Children and adolescents

EVOPAD 75?g/24 h transdermal patches should not be used in children.

Use of other medications

Inform your doctor or pharmacist if you are using or have used recently other medications, including those purchased without a prescription.Your doctor will inform you about this.

It is especially important to inform your doctor if you are going to take or are taking any of the following medications, as they may interact withEVOPAD 75?g/24 h transdermal patchesand modify its effect: antiepileptic medications (e.g. phenobarbital, phenytoin, and carbamazepine), a blood pressure medication (bosentan), antibiotics and other anti-infectious medications (e.g. rifampicin, rifabutin, erythromycin, ketoconazole, nevirapine, efavirenz, ritonavir, nelfinavir), some anti-ulcer medications (cimetidine) and herbal preparations containing St. John's Wort - Hypericum perforatum. The effect of these latter preparations persists for up to two weeks after they have been discontinued.

HRT may affect the way other medications work:

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

Medications for hepatitis C virus (HCV) (e.g., combination regimen for HCV or 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. Evopad contains estradiol instead of ethinyl estradiol. It is unknown whether an increase in ALT levels may occur when Evopad is used with this combination regimen for HCV.

Pregnancy and lactation

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

Do not use EVOPAD 75?g/24 h transdermal patches if you are pregnant or want to become pregnant.

Do not useEVOPAD 75?g/24 h transdermal patchesif you are breastfeeding.

Driving and operating machinery

No adverse effects of EVOPAD 75?g/24 h transdermal patches have been reported on the ability to drive or operate machinery.

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

Remember to use your medication.

Do not discontinue treatment before your doctor tells you to, as symptoms of menopause may reappear.

If you estimate that the action of EVOPAD 75?g/24 h patches is too strong or weak, inform your doctor or pharmacist.

The EVOPAD 75?g/24 h patches must be applied twice a week, removing each used patch after 3-4 days.

Your doctor will indicate the duration of your treatment with EVOPAD 75?g/24 h patches.

-Cyclic treatment for 3 weeks, followed by a therapeutic rest period of 7 days in which vaginal bleeding may occur.

-Continuous treatment in cases of women without a uterus or in severe manifestations of estrogen deficiency during the therapeutic rest period.

Treatment with progestogen:

-In cyclic treatments of 21 days with estradiol, it is recommended to administer a progestogen concurrently in the last 12 or 14 days of the cycle (e.g., starting on day 8 or 10 of the cycle).

-In continuous treatments with estradiol, it is recommended to administer a progestogen concurrently for 12 or 14 consecutive days of the month/cycle of 28 days.

Vaginal bleeding may occur after discontinuation of progestogen in both treatment regimens.

Instructions for correct administration

Open the bags and, through the "S" incision, remove the two parts of the protective sheet. The adhesive part of the transdermal system must be placed immediately on clean, dry, intact, and healthy skin, pressing with your fingers during the time of application.

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

The patch can remain in place during bathing andshowering. Incase it peels off and does not reattach correctly, a new patch must be applied immediately.

Do not apply over or near the breasts.

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

If you use moreEVOPAD 75?g/24 h patches than you should

If you have used EVOPAD 75?g/24 h patches more than you should, inform your doctor or pharmacist.

It is unlikely that you will use more EVOPAD than you should 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 treatment, and therefore, the medication to be administered should be to alleviate symptoms. These symptoms may disappear if the patch is removed.

In case of overdose or accidental ingestion, consult the toxicology information service. Phone (91) 562 04 20.

If you forgot to use EVOPAD 75?g/24 h patches

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

If you forgot to change the patch on the day it was due, do not worry, change it as soon as possible. Resume treatment according to the initial planned cycle. The usual change day is maintained. Forgetting a dose may increase the likelihood of bleeding and spotting during the cycle. If you have doubts, consult your doctor or pharmacist.

Like all medications, this medication can cause side effects, although not everyone will experience them.

If you consider that any of the side effects you are experiencing are severe or if you notice any side effect not mentioned in this leaflet, inform your doctor or pharmacist.

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

Very common: Can affect more than 1 in 10 people

Common:Can affect up to 1 in 10 people

Uncommon: Can affect up to 1 in 100 people

Rare: Can affect up to 1 in 1,000 people

Very rare: Can affect up to 1 in 10,000 people

Unknown

In clinical trials of EVOPAD 75?g/24 h transdermal patches, the following adverse reactions have been described:

-Infections and infestations

?Common: genital molluscum (genital infection)

?Uncommon: genital candidiasis

• Malignant and unspecified neoplasms (including cysts and polyps)

?Rare: breast cancer

?Unknown: endometrial cancer

• Immune system disorders

• Uncommon: allergic reaction

• Metabolism and nutrition disorders

• Common: weight gain or loss

-Mental 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)

?Unknown: stroke

-Eye disorders

?Uncommon: visual disturbance

?Rare: intolerance to contact lenses

• Cardiac disorders

• Uncommon: palpitations
• Unknown: myocardial infarction

• Vascular disorders

?Uncommon: hypertension

?Rare: thrombosis (blood clots)

?Unknown: deep vein thrombosis (blood clots in veins)

• Respiratory, thoracic and mediastinal disorders

?Unknown: pulmonary embolism (blood clots in lungs)

• Gastrointestinal disorders

?Common: nausea, abdominal pain, diarrhea

?Uncommon: flatulence, difficult and laborious digestion

?Rare: abdominal distension, vomiting, flatulence

• Hepatobiliary disorders

?Rare: gallstones

• Skin and subcutaneous tissue disorders

?Common: itching, rash, dry skin

?Uncommon: skin discoloration, urticaria, skin redness with pain

?Rare: excessive hair growth in women (hirsutism), acne

?Unknown: severe skin swelling 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 and breast disorders

?Very common: menstrual irregularities

?Common: irregular or continuous uterine bleeding, prolonged and abundant menstrual bleeding, irregular vaginal bleeding, uterine cramps, vaginal inflammation, uterine wall growth, vaginal bleeding/uterine bleeding including spotting

• Uncommon: breast enlargement, menstrual pain, breast pain, breast tenderness

?Rare: benign uterine tumors (uterine fibroids), breast lumps, cervical polyps, premenstrual syndrome, breast enlargement, white discharge

• General disorders and administration site conditions

?Very common: itching at the application site, rash at the application site

?Common: pain, weakness, edema at the application site, redness at the application site, reaction at the application site, weight changes

?Uncommon: fluid accumulation in tissues, fluid accumulation in multiple body parts, fluid accumulation in legs and feet (edema)

?Rare: fatigue

• Investigations

• Common: weight gain

-Abnormal laboratory findings

?Uncommon: increased transaminases (liver function test)

Risk of tumor development:

This HRT increases the risk of breast cancer. There is a greater risk of development in women who use combined estrogen and progestogen therapy. The increased risk of breast cancer is greater as the duration of treatment increases.

This treatment is not recommended for women with an intact uterus. If you have a uterus, your doctor will prescribe another hormone, progesterone, for 12 days in each cycle to reduce the risk of endometrial cancer.

It has been observed that in long-term treatments with estrogen alone or combined, there is an increased risk of developing ovarian tumors.

Risk of thrombosis:

This hormone replacement therapy increases the risk of thrombosis (blood clots), with a greater risk during the first year of use.

Risk of cardiovascular disease:

The risk of cardiovascular disease may increase in women using combined therapy from the age of 60.

Risk of stroke:

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

In oral treatment with synthetic estrogens alone or combined with progestogens, the following adverse reactions have been reported:malignant or benign estrogen-dependent neoplasms (e.g. endometrial cancer), myocardial infarction, stroke, biliary tract alterations, skin and subcutaneous tissue disorders (chloasma, erythema multiforme, erythema nodosum, purpura, contact dermatitis, generalized pruritus, urticaria, and angioedema), probable dementia.

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

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

Reporting of adverse reactions:

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction not listed in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use: https://www.notificaram.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medication.

Keep out of sight and reach of children.

Do not store above25 °C.

Do not use EVOPAD 7575?g/24 h transdermal patches after the expiration date shown on the packaging.

Composition of EVOPAD 75?g/24 h transdermal patches

• The active ingredient is estradiol. Each transdermal patch contains 4.80 milligrams of estradiol, (which represents a release of 75 micrograms of estradiol every 24 hours).
• The other components are: Acrylic-acetate vinyl copolymer adhesive, Guar gum, Polyester film.

Appearance of the product and contents of the package

It is presented in boxes of eight square, transparent, self-adhesive transdermal patches, 0.2 millimeters thick to apply to the skin surface.

Holder of the marketing authorization and responsible for manufacturing

Holder:Theramex Ireland Limited

3rdFloor, Kilmore House,

Park Lane, Spencer Dock,

Dublin 1

D01 YE64

Ireland

Responsible for manufacturing:Aesica Pharmaceuticals GmbH

Alfred-Nobel-Str. 10

40789 Monheim am Rhein

Germany

Local representative of the holder of the marketing authorization:

Theramex Healthcare Spain, S.L.

Calle Martínez Villergas 52, Edificio C, planta 2ª

left.

28027 Madrid

Spain

Medicines should not be thrown into the drains or trash. Dispose of the packaging and medicines that you do not need at the SIGRE point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medicines that you do not need. In this way, you will help protect the environment.

OTHER PRESENTATIONS:

EVOPAD 25?g/24 h transdermal patches:Box with 8 patches.

EVOPAD 50?g/24 h transdermal patches:Box with 8 patches.

EVOPAD 100?g/24 h transdermal patches:Box with 8 patches.

This leaflet has been approved in 03/2024

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