Estraderm Matrix 50 micrograms/24 hours transdermal patches: detailed information

Patient Information Leaflet

Introduction

Patient Information Leaflet

Estraderm Matrix 50 micrograms/24 hours transdermal patches

Estradiol

Read the entire package leaflet carefully before starting to use 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, consult your doctor or pharmacist.
This medicine has been prescribed for you only; do not give it to others, even if they have the same symptoms as you, as it may harm them.
If you experience adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Package leaflet contents:

What Estraderm Matrix is and what it is used for
What you need to know before using Estraderm Matrix
How to use Estraderm Matrix
Possible side effects
How to store Estraderm Matrix
Contents of the pack and other information

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

Estraderm Matrix is a Hormone Replacement Therapy (HRT) that contains the female hormone of the oestrogen type.

Estraderm Matrix is used in postmenopausal women.

Estraderm Matrix is used for:

Relief of menopausal symptoms

During menopause, the amount of oestrogen produced by a woman's body decreases. This can cause symptoms such as sudden waves of heat in the face, neck and chest (hot flushes). Estraderm Matrix relieves these symptoms after menopause. Estraderm Matrix will only be prescribed to you if your symptoms are seriously affecting your daily life.

Prevention of osteoporosis

After menopause, some women may develop brittle bones (osteoporosis). Discuss with your doctor all available treatment options. If you are at high risk of fractures due to osteoporosis and other medicines are not suitable for you, Estraderm Matrix may be used to prevent osteoporosis after menopause.

2. What you need to know before using Estraderm Matrix

Medical history and regular check-ups

HRT carries risks that must be considered when deciding whether to start or continue treatment.

Experience in treating women with premature menopause (due to ovarian failure or surgery) is limited. If you have premature menopause, the risks of using HRT may differ. Please consult your doctor.

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

Once you have started treatment with Estraderm Matrix, you should visit your doctor for regular check-ups (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing Estraderm Matrix.

Have regular breast examinations 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 here, consult your doctor before using Estraderm Matrix.

Do not use Estraderm Matrix

if you have or have had breast cancer or suspect you may have it
if you have an estrogen-dependent cancer, such as cancer of the inner lining of the uterus (endometrium), or if there is suspicion you may have it
if you have abnormal vaginal bleeding
if you have excessive thickening of the inner lining of the uterus (endometrial hyperplasia) for which you are not receiving treatment
if you have or have had a blood clot in a vein (thrombosis), such as in the legs (deep vein thrombosis) or in the lung (pulmonary embolism)
if you have a blood clotting disorder (such as protein C deficiency, protein S deficiency, or antithrombin deficiency)
if you have or have recently had a disease caused by blood clots in the arteries, such as a heart attack, stroke, or angina pectoris
if you have or have had a liver disease and your liver function tests have not returned to normal
if you have a rare inherited blood disorder called porphyria
if you are allergic to estradiol or any of the other ingredients of this medicine (listed in section 6).

If you experience any of the above conditions for the first time while using Estraderm Matrix, stop treatment immediately and consult your doctor without delay.

Warnings and precautions

Inform your doctor if you suffer from or have previously suffered from any of the following conditions before starting treatment, as they may recur or worsen during treatment with Estraderm Matrix. In such cases, you should visit your doctor more frequently for periodic check-ups:

uterine fibroids
growth of the inner lining of the uterus outside the uterus (endometriosis) or history of excessive growth of the inner lining of the uterus (endometrial hyperplasia)
increased risk of developing blood clots (see “Blood clots in a vein (thrombosis)”)
increased risk of developing an estrogen-dependent cancer (for example, if your mother, sister, or grandmother had breast cancer)
increased blood pressure
liver disorder, such as a benign liver tumor
diabetes
gallstones
kidney disorders
severe migraine or headaches
an autoimmune disease affecting multiple organs of the body (systemic lupus erythematosus, SLE)
epilepsy
asthma
a disease affecting 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 caused by abnormal thyroid gland function resulting in insufficient hormone levels requiring treatment)
hereditary or acquired angioedema (a disease that may cause episodes of rapid swelling of the hands, feet, face, lips, eyes, tongue, or throat with airway or gastrointestinal tract blockage).

Stop using Estraderm Matrix and see a doctor immediately

If you experience any of the following while using HRT:

any of the conditions listed in the section “Do not use Estraderm Matrix”
yellowing of the skin or whites 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 hives, together with difficulty breathing, suggesting angioedema
a significant increase in your blood pressure (symptoms may include headache, fatigue, dizziness)
new-onset migraine-type headaches
if you become pregnant
if you notice signs of a blood clot, such as:
painful swelling and redness in the legs
sudden chest pain
difficulty breathing

For more information, see “Blood clots in a vein (thrombosis)”.

Note: Estraderm Matrix is not a contraceptive. If less than 12 months have passed since your last menstrual period or if you are under 50 years of age, you may still need additional contraceptive measures to prevent pregnancy. Speak with your doctor for advice.

HRT and cancer

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

Taking HRT with estrogen-only products increases the risk of developing thickening of the uterine lining (endometrial hyperplasia) and cancer of the uterine lining (endometrial cancer).

Adding a progestogen to estrogen therapy for at least 12 days of each 28-day cycle protects 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 your uterus has been removed (hysterectomy), ask your doctor whether you can safely be treated with this medicine without using a progestogen.

In women aged 50 to 65 years who have a uterus and are not using HRT, an average of 5 out of 1000 will be diagnosed with cancer of the uterine lining.

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

Unexpected bleeding

You will experience monthly bleeding (called withdrawal bleeding) while using Estraderm Matrix. However, if you experience unexpected vaginal bleeding or spotting in addition to your monthly bleeding that:

continues beyond 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

Available data show that the use of hormone replacement therapy (HRT), whether combined estrogen-progestogen or estrogen-only, increases the risk of breast cancer. The additional risk depends on how long you use HRT. The additional risk becomes apparent after 3 years of use. After stopping HRT, the additional risk decreases 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 not using HRT, an average of 13 to 17 out of 1000 will be diagnosed with breast cancer over a 5-year period.

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

Examine your breasts regularly. See your doctor if you notice any changes such as:

dimples or indentations in the skin
changes in the nipples
any lump you can see or feel

In addition, you are advised to join mammography screening programs when offered. For screening mammography, it is important that you inform the nurse/healthcare professional performing the X-rays that you are using HRT, as this medicine may increase breast density, which can affect mammogram results. When breast density is increased, mammography may not detect all lumps.

Ovarian cancer

Ovarian cancer occurs less frequently than breast cancer. The use of HRT with estrogen-only or combined estrogen-progestogen therapy 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 per 2000 women are observed over a 5-year period. In women using HRT for 5 years, about 3 cases per 2000 women are observed (i.e., about 1 additional case).

Effect of HRT on the heart and circulation

Blood clots in a vein (thrombosis)

The risk of blood clots in veins is approximately 1.3 to 3 times higher in HRT users than in non-users, especially during the first year of treatment.

Blood clots can be serious, and if one travels to the lungs, it can cause chest pain, difficulty breathing, fainting, or even death.

Your risk of developing a blood clot in your veins increases with age and if you have any of the following conditions. Inform your doctor if you are in any of these 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 are considerably overweight (BMI >30 kg/m²)
you have a blood clotting disorder requiring long-term treatment with a medication used to prevent blood clots
if any of your close relatives has ever had a blood clot in the leg, lung, or another 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 fifties not taking HRT, an average 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 fifties taking combined estrogen-progestogen HRT for 5 years, there will be 9 to 12 cases per 1000 users (i.e., 5 additional cases).

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

Heart disease (heart attack)

There is no evidence that HRT prevents heart attacks.

Women over 60 years of age using combined estrogen-progestogen HRT are slightly more likely to develop heart disease than those not taking any hormone replacement therapy.

In women who have had their uterus removed and are using estrogen-only therapy, 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 fifties not taking HRT, an average of 8 out of 1000 will likely suffer a stroke over a 5-year period.

In women in their fifties taking HRT, 11 out of 1000 will likely suffer a stroke over a 5-year period (i.e., 3 additional cases).

Other conditions HRT does not prevent memory loss. There is some evidence of an increased risk of memory loss in women who start HRT after age 65. Talk to your doctor for advice.

Children

Estraderm Matrix must not be used in children.

Other medicines and Estraderm Matrix

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

medicines for epilepsy (such as phenobarbital, phenytoin, carbamazepine);
medicines for tuberculosis (such as rifampicin, rifabutin);
medicines for HIV infection (such as nevirapine, efavirenz, ritonavir, nelfinavir);
herbal preparations containing St. John's wort (Hypericum perforatum).

HRT may affect how other medicines work:

medicines for epilepsy (lamotrigine), as the frequency of seizures may increase.
medicines for hepatitis C virus (HCV) (such as the combination regimen of ombitasvir/paritaprevir/ritonavir with or without dasabuvir, as well as the regimen with glecaprevir/pibrentasvir), which may cause increases in liver function test results in blood tests (elevated liver enzyme ALT) in women using combined hormonal contraceptives (CHCs) containing ethinylestradiol. Estraderm Matrix contains estradiol instead of ethinylestradiol. It is not known whether elevated ALT liver enzyme levels may occur when using Estraderm Matrix with HCV combination regimens.
other anti-infective medicines (such as ketoconazole, erythromycin)

Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those obtained without a prescription, herbal medicines, 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 medicine may affect the results of certain tests. Some laboratory tests, such as glucose tolerance test or thyroid function tests, may be affected by treatment with Estraderm Matrix.

Pregnancy and breastfeeding

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

Estraderm Matrix must not be used during breastfeeding.

Driving and operating machinery

Estraderm Matrix does not affect the capacity to drive or operate machinery.

3. How to use Estraderm Matrix

Follow exactly the instructions for administering this medicine as given by your doctor. If in doubt, consult your doctor again.

Remember to apply Estraderm Matrix.

Your doctor will aim to prescribe the lowest effective dose to treat your symptoms for the shortest possible duration. Speak with your doctor if you feel that this dose is too strong or too weak.

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

Estraderm Matrix may be administered either continuously or cyclically:

Continuous administration: uninterrupted application, using 2 patches per week.
Cyclic administration: treatment for 3 weeks (2 patches per week) followed by 1 week without medication.

Your doctor will advise you which treatment regimen is most suitable for you.

If you have not had a hysterectomy (removal of the uterus), your doctor will likely prescribe tablets containing another hormone, progesterone, to be taken regularly for part of each month. Your doctor will explain how to take these tablets. After finishing the progesterone tablets each month, you may experience vaginal bleeding.

Follow your doctor's instructions on how to use the patches. If you feel that the effect of Estraderm Matrix is too strong or too weak, inform your doctor or pharmacist.

HOW TO APPLY ESTRADERM

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

Each patch is sealed in a protective pouch and contains the active substance in an adhesive layer that adheres directly to the skin. This adhesive layer is covered by a transparent film larger than the patch itself, divided into two parts by a slit. The transparent film (release liner) must be removed before applying the patch.

Open the pouch along the notch (do not use scissors, as this may damage the patch) and remove the patch (Fig. 1).

Make sure you have removed the previous patch before applying a new one.

Two hands holding and breaking a tablet or pill into two equal parts along a central dotted line

Fig. 1

Remove the patch from the pouch, first peel off the smaller part of the release liner, then the larger part, and discard them. Avoid touching the adhesive surface (Fig. 2, 3), and remember not to fold the patch, as this could cause the adhesive sides to stick together. (Figs. 2 and 3).

Two line drawings showing hands opening and separating a container or medical device into two distinct parts

Figs. 2-3

Apply the patch immediately to an area below the waist (abdomen, buttocks, or lower back) and press firmly for 10–20 seconds (Fig. 4). Ensure it adheres well, especially around the edges. Do not test adhesion by pulling on the patch once applied.

(Fig. 4).

Line drawing of a hand applying a small rectangular adhesive bandage to the upper thigh of a person

Fig. 4

Choose an area that develops few wrinkles with movement and has minimal friction from clothing, otherwise the patch may come loose. The skin in the selected area must be dry and free of oil (otherwise the patch will not adhere properly), so do not use creams, lotions, or other cosmetics on the site where the patch will be applied. Also avoid areas with excessive hair or where the skin is damaged or irritated.

Experience shows that skin irritation is less frequent on the buttocks. Therefore, whenever possible, Estraderm Matrix should be applied in this area. Do not apply the Estraderm Matrix patch on the breasts.

Provided the patch is correctly applied, you may shower, bathe, swim, or exercise. If the patch detaches after bathing or showering, apply a new patch once the skin is cool and dry. Do not apply the patch on skin covered with sweat or immediately after a very hot bath or shower.

The chosen area should be covered with clothing, as it must not be exposed to direct sunlight or artificial UV light.

You should change the patch every 3 or 4 days to ensure your body receives a regular dose of estradiol. The easiest way is to change it on the same two days each week, e.g., Monday and Thursday. Choose two days that are easy for you to remember. To help you remember, a strip of labels is provided in the package; attach the label with your selected days to the inside flap of the box. Discard the remaining labels.

Do not apply the patch in the same location two times in a row. After one week, you may reapply a new patch to a previously used area. As long as you strictly follow these instructions, you should have no problems wearing the patches for 3–4 days.

If the patch becomes detached, you may reapply the same patch to a different area of skin, provided the area is clean, dry, and free of creams or lotions. If the patch does not adhere properly, use a new one. Regardless of the day this occurs, resume changing the patch on your originally scheduled days.

After use, remove the patch, fold it with the adhesive side inward, and dispose of it safely, ensuring it is out of reach of children.

Your doctor will advise you on the duration of your treatment with Estraderm Matrix. Do not stop treatment without first consulting your doctor.

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

If you need surgery

If you are scheduled for surgery, inform your surgeon that you are using Estraderm Matrix. You may need to stop using Estraderm Matrix 4 to 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 restart treatment with Estraderm Matrix.

If you use more Estraderm Matrix than you should

If you use more Estraderm Matrix than prescribed, contact your doctor or pharmacist immediately. Due to the method of administration, poisoning with this medicine is unlikely.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicology Information Service at telephone number 915 620 420, indicating the medication and the amount taken.

If you forget to use Estraderm Matrix

If you forget to change the patch, apply a new one as soon as you remember. Regardless of the day, resume changing the patch on your originally scheduled days.

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

4. Possible adverse effects

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

The following conditions are observed more frequently in women treated with HRT compared to women not treated with HRT:

Breast cancer
Abnormal growth of the inner lining of the uterus (endometrial hyperplasia) or cancer of the inner lining 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 HRT is started at age 65 or older

For more information about these adverse effects, see section 2.

Some adverse effects can be serious:

Signs of a severe allergic reaction: rash, itching, hives, difficulty breathing, sneezing or coughing, feeling faint, dizziness, altered consciousness, hypotension with or without mild generalized itching, skin redness, swelling of the face, throat, lips, tongue, skin, and periorbital edema.
Signs of jaundice: yellowing of the eyes or skin, darkening of the urine, and skin itching.
Signs or symptoms of blood clots that may form in your body: pain in the calves, thighs, or chest, sudden shortness of breath, coughing up blood, and dizziness.
Signs or symptoms of myocardial infarction: chest pain, dizziness, nausea, shortness of breath, irregular pulse.
Signs or symptoms of stroke: collapse, tingling or weakness in arms and legs, headache, dizziness and confusion, vision disturbances, difficulty swallowing, difficulty speaking, and loss of speech.

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

Some adverse effects are very common:

(These adverse effects may affect at least 1 in every 10 patients)

Breast pain or discomfort
Sudden bleeding
Itching under the patch, pain, and redness of the skin after removing the patch (signs of a reaction at the application site include bleeding, bruising, burning, discomfort, dryness, boils, edema, erythema, inflammation, irritation, pain, tiny bumps, rash, skin discoloration, skin pigmentation, swelling, hives, and blisters).