Introduction

Package Insert: Information for the User

Estraderm Matrix 50 micrograms/24 hours Transdermal Patches

Estradiol

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 you should not give it to others who may 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 not listed in this package insert. See section 4.

6. Contents of the pack and additional information

1. What is Estraderm Matrix and what is it used for

Estraderm Matrix is a Hormonal Replacement Therapy (HRT) that contains the female sex hormone estrogen.

Estraderm Matrix is used in postmenopausal women.

Estraderm Matrixis usedfor:

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, brief episodes of heat in the face, neck, and chest (hot flashes). Estraderm Matrix relieves these symptoms after menopause. Estraderm Matrix will only be prescribed if your symptoms seriously affect your daily life

Prevention of osteoporosis

After menopause, some women may develop brittle bones (osteoporosis). Consult with your doctor about all available treatment options. If you have a high risk of suffering fractures due to osteoporosis and other medications are not suitable for you, you may use Estraderm Matrix to prevent osteoporosis after menopause.

2. What you need to know before starting to use Estraderm Matrix

Medical History and Regular Reviews

The use of THS involves risks that should be considered when deciding to use it or 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 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 started on Estraderm Matrix treatment, 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 Estraderm Matrix.

Perform regular breast checks, as recommended by your doctor.

Do Not Use Estraderm Matrix

If any of the following apply to you. If you are unsure about any of the points described below, consult your doctor before using Estraderm Matrix.Consult your doctorbefore using Estraderm Matrix.

Do Not Use Estraderm Matrix

if you have or have hadbreast canceror if you suspect 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 experienceabnormal vaginal bleeding
if you have anexcessive thickening of the uterine lining(endometrial hyperplasia) for which you are not receiving treatment
if you have or have hada blood 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 aanginaof the chest
if you have or have had aliver diseaseand your liver function tests have not normalized
if you have a rare blood disorder calledporphyriathat is inherited
if you are allergic to estradiol, or to any of the other components of this medication (including those listed in section 6).

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

Warnings and Precautions

Inform your doctor if you experience or have experienced any of the following situations before starting treatment, as they may recur or worsen during treatment with Estraderm Matrix. In that case, you should visit your doctor more frequently for regular reviews:

fibroids within the uterus
growth of the uterine lining outside the uterus (endometriosis) or history of excessive growth of the uterine lining (endometrial hyperplasia)
increased risk of developing blood clots (see “Blood clots in a vein (thrombosis)”)
increased risk of developing a cancer that depends on estrogen (such as when your mother, sister, or grandmother have had breast cancer)
increased blood pressure
liver disorder, such as a benign tumor in the liver
diabetes
gallstones
renal disorders
migraine or severe headache
a disease of the immune system that affects multiple 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
hypothyroidism (a condition that occurs due to abnormal functioning of the thyroid gland that produces insufficient hormone that requires treatment)
hereditary or acquired angioedema (a disease that can cause rapid swelling of the hands, feet, face, lips, eyes, tongue, throat, with airway or digestive tract blockage).

Stop using Estraderm Matrix 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 Estraderm Matrix”
yellowing of the skin or white of the eyes (jaundice). This may be a sign of liver disease
swelling of the face, tongue, and/or throat and/or difficulty swallowing or urticaria, along with difficulty breathing that 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:Estraderm Matrix is not a contraceptive. If you have had less than 12 months since your last menstrual period or are less than 50 years old, you may still need additional contraceptive measures to prevent pregnancy. Talk to your doctor for advice.

THS and Cancer

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

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

The addition of a progestogen to estrogen treatment for at least 12 days of each 28-day cycle will protect against this additional risk. Therefore, if you still have your uterus, your doctor will prescribe a progestogen separately for at least 12 days per cycle to reduce the risk of endometrial cancer.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 their 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 on THS treatment with estrogen-only, 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 (known as menstrual bleeding) while using Estraderm Matrix.However, if you experience unexpected bleeding or spotting of blood apart from your monthly bleeding, which:

continues for more than the first 6 months
starts after you have been using Estraderm Matrix for more than 6 months
continues after you have stopped using Estraderm Matrix

See your doctor as soon as possible.

Breast Cancer

The available data show that the use of hormone replacement therapy (HRT) with estrogen-progestogen combinations or with estrogen-only increases the risk of breast cancer. The additional risk depends on the duration of 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 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 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 will be diagnosed over a 10-year period.

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

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

Check 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 join a mammography screening program when offered to you. For mammography screening, it is essential that you inform the healthcare professional/nurse who directs the X-rays that you are using HRT, as this medication may increase the density of your breasts, which may affect the result of the mammogram. When the breast density increases, the mammogram may not detect all lumps.

Endometrial Cancer

Endometrial cancer occurs less frequently than breast cancer. The use of HRT with estrogen-only or with estrogen-progestogen combinations has been associated with a slightly higher risk of endometrial cancer.

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

Effect of HRT on the Heart and Circulation

Blood Clots in a Vein (Thrombosis)

The risk ofblood clots in the 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 you are in any of the following situations:

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 overweight (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 Estraderm Matrix 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 combined with estrogen-progestogen for 5 years, there will be 9 to 12 cases per 1000 users (i.e., 5 additional cases).

In women in their 50s who have had their uterus removed and have been treated with HRT with estrogen-only 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 will prevent a heart attack.

Women over 60 years old who use HRT with estrogen and progestogen are slightly more likely to develop heart disease than those who do not take any hormone replacement therapy.

In women who have had their uterus removed and are only on estrogen treatment, there is no increased risk of heart disease.

Stroke

The risk of stroke is approximately 1.5 times higher in HRT users than in non-users. The number of additional stroke cases due to HRT use increases 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 treated with HRT, 11 out of 1000 are expected to have a stroke over a 5-year period (i.e., 3 additional cases).

Other ConditionsHRT does not prevent memory loss. There is some evidence of a higher risk of memory loss in women who start HRT after 65 years. Talk to your doctor for advice.

Children

Estraderm Matrix should not be used in children.

Other Medications and Estraderm Matrix

Some medications may interfere with the effect of Estraderm Matrix. This may cause irregular bleeding. This occurs with the following medications:

medications forepilepsy(such as phenobarbital, phenytoin, carbamazepine);
medications fortuberculosis(such as rifampicin, rifabutin);
medications forHIV infection(such as nevirapine, efavirenz, ritonavir, nelfinavir);
preparations based on medicinal plants containingSt. John's Wort(Hypericum perforatum).

HRT may affect how other medications work:

medications for epilepsy (lamotrigine), as the frequency of seizures may increase.
medications forhepatitis C virus (HCV)(such as a combination regimen of ombitasvir/paritaprevir/ritonavir with or without dasabuvir, as well as a regimen with glecaprevir/pibrentasvir) that may produce increases in liver function test results (elevated ALT levels) in women using combined hormonal contraceptives (CHCs) that contain ethinylestradiol. Estraderm Matrix contains estradiol instead of ethinylestradiol. It is not known if an increase in ALT levels can occur when using Estraderm Matrix with HCV combination regimens.
other anti-infective medications (such as ketoconazole, erythromycin)

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

Laboratory Tests

If you need a blood test, inform your doctor or laboratory staff that you are using Estraderm Matrix, as this medication may affect the results of some tests.Some laboratory tests, such as the glucose tolerance test or thyroid function test, may be affected by Estraderm Matrix treatment.

Pregnancy and Breastfeeding

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

Estraderm Matrix should not be used during breastfeeding

Driving and Operating Machines

Estraderm Matrix does not affect the ability to drive or operate machines.

3. How to Use Estraderm Matrix

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

Remember to apply Estraderm Matrix.

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.

Estraderm Matrix will be applied twice a week, that is, the patch should be changed every 3 or 4 days.

Estraderm Matrix can be administered both continuously and cyclically:

Continuous administration: uninterrupted application, using 2 patches weekly.
Cyclic administration: 3-week treatment (2 patches weekly) followed by a week without medication.

Your doctor will indicate which treatment schedule is most suitable for you.

If you have not had your uterus removed (hysterectomy), your doctor will probably prescribe tablets containing another hormone, progesterone, for you to take regularly every month. Your doctor will explain how to take these tablets. After finishing taking the progesterone tablets every month, you may experience vaginal bleeding.

Follow the instructions given by your doctor on how to use the patches. If you estimate that the action of Estraderm Matrix is too strong or weak, inform your doctor or pharmacist.

HOW TO APPLY ESTRADERM

You must wear the patch at all times. Change it every 3 or 4 days.

Each patch is sealed in a protective envelope and contains the active substance in an adhesive layer that adheres directly to the skin. This adhesive layer is covered by a transparent and larger-sized sheet, divided into two parts by a groove. The transparent sheet (removable sheet) will be removed before applying the patch.

Open the envelope by the notch (do not use scissors to avoid damaging the patch) and remove the patch (Fig. 1).

Make sure you do not have the previous patch before applying the new patch.

Fig. 1

Remove the patch from the envelope, remove the smaller part of the removable sheet first, then the larger one and dispose of them. Be careful not to touch the adhesive (Fig. 2, 3) and remember that the patch should not be folded so that the adhesive layers do not come into contact. (Fig. 2 and 3).

Figs. 2-3

Apply the patch immediately to an area below the waist (abdomen, buttocks, or lower back) and press it for 10-20 seconds (Fig. 4). Make sure it sticks well, especially at the edges. Do not check the patch's adhesion by pulling it once applied.

(Fig. 4).

Fig. 4

Choose an area where few wrinkles form due to movement and little friction with clothing, otherwise the patch will come off. The skin of the selected area should be dry and free of grease (since if not the patch will not stick), therefore do not use creams, lotions, or other cosmetics on the area where the patch is applied; also avoid areas with excessive hair and skin alterations or irritation.

Experience indicates that skin irritation is less in the buttocks. Therefore, whenever possible, Estraderm Matrix will be applied in this area.Do not place the Estraderm Matrix patch on the breasts.

As long as the patch has been applied correctly, you can take a shower, bathe, swim, or exercise. If the patch comes off after a bath or shower, apply a new patch when the skin is cold and dry. Do not apply the patch to greasy skin or after a hot bath or shower.

The selected area should be covered with clothing since it should not receive direct sunlight or artificial light.

You should change the patch every 3 or 4 days to ensure that your body receives the necessary dose of estradiol regularly. To do this, it is simplest to change it on the same two days of the week, for example, Monday and Thursday. Choose two days that you can easily remember. To remember them, you will find a strip of labels in the box; stick the label with the selected days to the inside of the box. Dispose of the rest of the labels.

Do not place the patch twice in a row in the same place.You can apply a new patch to a previously used area after a week. As long as you strictly follow these instructions, you will not have problems wearing the patches for 3-4 days.

If the patch comes off, you can place the same patch on a different area of the skin. Make sure it is clean, dry, and free of creams or lotions. If the patch does not stick correctly to the skin, use a new one. It does not matter on which day this happens, go back to changing the patch on the same days as initially planned.

Once the patch has been used, remove it, fold it with the adhesive towards the inside, and dispose of it, making sure it is out of reach of children.

Your doctor will indicate the duration of your treatment with Estraderm Matrix. Do not suspend treatment without consulting your doctor first.

Estraderm Matrix should be used for as long as necessary, usually for several months or more. This will help control your symptoms and prevent bone loss that appears after menopause.

If you need surgery

If you are undergoing a surgical procedure, inform your surgeon that you are using Estraderm Matrix. You may need to stop using Estraderm Matrix between 4 and 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 Estraderm Matrix again.

If you use more Estraderm Matrix than you should

If you use more Estraderm Matrix than you should, contact your doctor or pharmacist immediately. Given the administration method, it is unlikely that you will experience intoxication with this medication.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicological Information Service. Phone 915 620 420, indicating the medication and the amount used.

If you forgot to use Estraderm Matrix

If you forget to change the patch, apply a new one as soon as you remember. It does not matter on which day this happens, go back to changing the patch on the same days as initially planned.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.Inform your doctor if you experience any of the following side effects.

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 or older

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

Some side effects can be severe:

Signs of a severe allergic reaction:eruption, itching, urticaria, difficulty breathing, sneezing or coughing, dizziness, vertigo, altered consciousness, hypotension with or without generalized mild itching, skin redness, facial swelling, throat, lips, tongue, skin, and periorbital edema.
Signs of jaundice: yellow color of the eyes or skin, darkening of the urine, and skin itching.
Signs or symptoms of thrombi that may form in your body: leg pain, thigh pain, chest pain, sudden shortness of breath, coughing with blood, and dizziness.
Signs or symptoms of myocardial infarction: chest pain, dizziness, nausea, shortness of breath, irregular pulse.
Signs or symptoms ofstroke: collapse, tingling or weakness of the arms and legs, headache, dizziness, and confusion, visual disturbances, difficulty swallowing, difficulty speaking, and loss of speech.

If you experience any of these side effects, stop using this medicine and inform your doctor immediately.

Some side effects are very common:

(These side effects can affect at least 1 in 10patients)

breast pain or discomfort
unusual bleeding
itching under the patch, pain, and skin redness after removing the patch(the signs of a reaction at the application site include bleeding, hematomas, burning, discomfort, dryness, furuncles, edema, erythema, inflammation, irritation, pain, small bumps, rash, skin discoloration, pigmentation, swelling, urticaria, and vesicles).