Evorel 25 Patches

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Evorel is and what it is used for
2. What you need to know before you use Evorel
3. How to use Evorel
4. Possible side effects
5. How to store Evorel
6. Contents of the pack and other information

• The symptoms of the menopause (see ‘What is the menopause?’)

• Prevent osteoporosis (fragile bones) in women who have had the menopause and are most likely to have bone problems. Evorel 50, 75 and 100 are only used if other medicines for osteoporosis have been tried first and they have not worked.

Women produce oestrogen hormones from their ovaries throughout their adult life. These hormones are important in sexual development and control of the menstrual cycle.

The menopause happens when the level of hormones produced by the ovaries goes down. This is a gradual process. During this time the levels of oestrogen can go up and down. This can cause:

• Hot flushes, night sweats or mood swings
• Vaginal problems such as dryness or itching
• Uncomfortable or painful sexual intercourse

You may get the same symptoms if you have had your ovaries taken out in an operation.

Relief of symptoms occurring after menopause

During the menopause, the amount of the oestrogen produced by a woman’s body drops. This can cause symptoms such as hot face, neck and chest ("hot flushes"). Evorel alleviates these symptoms after menopause. You will only be prescribed Evorel if your symptoms seriously hinder your daily life.

Prevention of osteoporosis

After the menopause some women may develop fragile bones (osteoporosis). You should discuss all available options with your doctor.

If you are at an increased risk of fractures due to osteoporosis and other medicines are not suitable for you, you can use Evorel to prevent osteoporosis after menopause.

Evorel patches replace the oestrogen that is normally released by the ovaries. However, in women who still have a womb, taking an oestrogen hormone regularly may cause the lining of your womb to build up and get thicker.

• This means it is necessary to add a progestogen hormone to the oestrogen
• This helps shed the lining of the womb and stop any problems happening

Evorel is not a contraceptive.

The use of HRT carries risks which need to be considered when deciding whether to start taking it, or whether to carry on taking it.

The experience in treating women with a premature menopause (due to ovarian failure or surgery) is limited. If you have a premature menopause the risks of using HRT may be different. Please talk to your doctor.

Before you start (or restart) HRT, your doctor will ask about your own and your family’s medical history. Your doctor may decide to perform a physical examination. This may include an examination of your breasts and/or an internal examination, if necessary.

Once you have started on Evorel you should see your doctor for regular check-ups (at least once a year). At these check-ups, discuss with your doctor the benefits and risks of continuing with Evorel.

Go for regular breast screening, as recommended by your doctor.

If any of the following applies to you. If you are not sure about any of the points below, talk to your doctor before taking Evorel

• You have or have ever had breast cancer, or if you are suspected of having it;
• You have cancer which is sensitive to oestrogens such as cancer of the womb lining (endometrium), or if you are suspected of having it
• You have any unexplained vaginal bleeding;
• You have excessive thickening of the womb lining (endometrial hyperplasia) that is not being treated;
• You have or have ever had a blood clot in a vein (thrombosis) such as in the legs (deep venous thrombosis) or the lungs (pulmonary embolism);
• You have a blood clotting disorder (such as protein C, protein S or antithrombin deficiency);
• You have or recently have had a disease caused by blood clots in the arteries, such as a heart attack, stroke or angina;
• You have or have ever had a liver disease and your liver function tests have not returned to normal;
• You have a rare blood problem called “porphyria” which is passed down in families (inherited);
• You are allergic (hypersensitive) to estradiol or any of the other ingredients of Evorel (listed in section 6 Further information).

If any of the above conditions appear for the first time while taking Evorel, stop taking it at once and consult your doctor immediately.

Evorel should not be used by children.

Tell your doctor if you have ever had any of the following problems, before you start the treatment, as these may return or become worse during treatment with Evorel. If so, you should see your doctor more often for check-ups:

• fibroids inside your womb;
• growth of womb lining outside your womb (endometriosis) or a history of excessive growth of the womb lining (endometrial hyperplasia);
• increased risk of developing blood clots (see “Blood clots in a vein (thrombosis)”);
• increased risk of getting an oestrogen-sensitive cancer (such as having a mother, sister or grandmother who has had breast cancer);
• high blood pressure;
• a liver disorder, such as a benign liver tumor;
• diabetes;
• gallstones;
• migraine or severe headaches;
• a disease of the immune system that affects many organs of the body (systemic lupus erythematosus, SLE);
• epilepsy;
• asthma;
• a disease affecting the eardrum and hearing (otosclerosis);
• a very high level of fat in your blood (triglycerides);
• fluid retention due to cardiac or kidney problems;
• hereditary and acquired angioedema;
• mastopathy.

Make sure that you:

• Go for regular breast screening and cervical smear tests
• Regularly check your breasts for any changes such as dimpling of the skin, changes in the nipple, or any lumps you can see or feel

If you notice any of the following when taking HRT:

• any of the conditions mentioned in the ‘DO NOT take Evorel section;
• yellowing of your skin or the whites of your eyes (jaundice). These may be signs of a liver disease;
• swollen face, tongue and/or throat and/or difficulty swallowing or hives, together with difficulty breathing which are suggestive of an angioedema;
• a large rise in your blood pressure (symptoms may be headache, tiredness, dizziness);
• migraine-like headaches which happen for the first time;
• if you become pregnant;
• if you notice signs of a blood clot, such as:
  • painful swelling and redness of the legs;
  • sudden chest pain;
  • difficulty in breathing;

For more information, see ‘Blood clots in a vein (thrombosis)’

Note: Evorel is not a contraceptive. If it is less than 12 months since your last menstrual period or you are under 50 years old, you may still need to use additional contraception to prevent pregnancy. Speak to your doctor for advice.

As well as benefits, HRT has some risks. Consider the following when deciding to take or continue HRT.

Excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the lining of the womb (endometrial cancer)

Taking oestrogen-only HRT will increase the risk of excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the womb lining (endometrial cancer).

Taking a progestogen in addition to the oestrogen for at least 12 days of each 28-day cycle protects you from this extra risk. So, your doctor will prescribe a progestogen separately if you still have your womb. If you have had your womb removed (a hysterectomy), discuss with your doctor whether you can safely take this product without a progestogen.

In women who still have a womb and who are not taking HRT, on average, 5 in 1000 will be diagnosed with endometrial cancer between the ages of 50 and 65.

For women aged 50 to 65 who still have a womb and who take oestrogen-only HRT, between 10 and 60 women in 1000 will be diagnosed with endometrial cancer (i.e. between 5 and 55 extra cases), depending on the dose and for how long it is taken.

Evorel 100 contains a higher dose of oestrogens than other oestrogen-only HRT products. The risk of endometrium cancer when using Evorel 100 together with a progestogen is not known.

Breast cancer

Evidence shows that taking combined oestrogen-progestogen or oestrogen-only hormone replacement therapy (HRT) increases the risk of breast cancer. The extra risk depends on how long you use HRT. The additional risk becomes clear within a 3 years of use. After stopping HRT the extra risk will decrease with time, but the risk may persist for 10 years or more if you have used HRT for more than 5 years.

Compare

Women aged 50 to 54 who are not taking HRT, on average 13 to 17 in 1000 will be diagnosed with breast cancer over a 5-year period.

For women aged 50 who start taking oestrogen-only HRT for 5 years, there will be 16-17 cases in 1000 users (i.e. an extra 0 to 3 cases).

For women aged 50 who start taking oestrogen-progestogen HRT for 5 years, there will be 21 cases in 1000 users (i.e.an extra 4-8 cases).

Women aged 50 to 59 who are not taking HRT, on average, 27 in 1000 will be diagnosed with breast cancer over a 10-year period.

For women aged 50 who start taking oestrogen-only HRT for 10 years, there will be 34 cases in 1000 users (i.e. an extra 7 cases)

For women aged 50 who start taking oestrogen-progestogen HRT for 10 years, there will be 48 cases in 1000 users (i.e. an extra 21 cases).

Regularly check your breasts. See your doctor if you notice any changes such as:

• Dimpling of the skin
• Changes in the nipple
• Any lumps you can see or feel

Make an appointment to see your doctor as soon as possible.

Additionally, you are advised to join mammography screening programs when offered to you. For mammogram screening, it is important that you inform the nurse/healthcare professional who is actually taking the x-ray that you use HRT, as this medication may increase the density of your breasts which may affect the outcome of the mammogram. Where the density of the breast is increased, mammography may not detect all lumps.

Ovarian cancer

Ovarian cancer (cancer of the ovaries) is rare, much rarer than breast cancer. The use of oestrogen-only or combined oestrogen-progestogen HRT 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 who are not taking HRT, about 2 women in 2000 will be diagnosed with ovarian cancer over a 5-year period. For women who have been taking HRT for 5 years, there will be about 3 cases per 2000 users (i.e. about 1 extra case).

Blood clots in a vein (thrombosis)

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

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

You are more likely to get a blood clot in your veins as you get older and if any of the following applies to you. Inform your doctor if any of these situations applies to you:

• you are unable to walk for a long time because of major surgery, injury or illness (see also section 3, If you need to have surgery);
• you are seriously overweight (BMI >30 kg/m2);
• you have any blood clotting problem that needs long-term treatment with a medicine used to prevent blood clots;
• if any of your close relatives has ever had a blood clot in the leg, lung or another organ;
• you have systemic lupus erythematosus (SLE);
• you have cancer;

For signs of a blood clot, see “Stop using Evorel and see a doctor immediately”.

Compare

Looking at women in their 50s who are not taking HRT, on average, over a 5-year period, 4 to 7 in 1000 would be expected to get a blood clot in a vein.

For women in their 50s who have been taking oestrogen-progestogen HRT for over 5 years, there will be 9 to 12 cases in 1000 users (i.e.an extra 5 cases).

For women in their 50s who have had their womb removed and have been taking oestrogen-only HRT for over 5 years, there will be 5 to 8 cases in 1000 users (i.e. 1 extra case).

Heart disease (heart attack)

There is no evidence that HRT will prevent a heart attack.

Women over the age of 60 years who use oestrogen-progestogen HRT are slightly more likely to develop heart disease than those not taking any HRT.

For women who have had their womb removed and are taking oestrogen-only therapy there is no increased risk of developing a heart disease.

Stroke

The risk of getting stroke is about 1.5 times higher in HRT users than in non-users. The number of extra cases of stroke due to use of HRT will increase with age.

Compare

Looking at women in their 50s who are not taking HRT, on average, 8 in 1000 would be expected to have a stroke over a 5-year period. For women in their 50s who are taking HRT, there will be 11 cases in 1000 users, over 5 years (i.e. an extra 3 cases).

If you get migraine-type headaches which you cannot explain

• See a doctor as soon as possible
• Do not take any more HRT until your doctor says you can

These headaches may be an early warning sign of a stroke

Other conditions

If you have brown patches on your face or body (chloasma) or have a history of them, you may need to keep out of the sun or away from sunbeds (these patches may not completely disappear again)

Dementia

Evorel and medicines like it will not stop memory loss (dementia). Women who start using medicines like Evorel after the age of 65 may have a small increase in the risk of dementia.

Some medicines may interfere with the effect of Evorel. This might lead to irregular bleeding. This applies to the following medicines:

• Medicines for epilepsy (such as phenobarbital, phenytoin and carbamazepin);
• Medicines for tuberculosis (such as rifampicin, rifabutin);
• Medicines for HIV infection (such as nevirapine, efavirenz, ritonavir and nelfinavir);
• Herbal remedies containing St John’s Wort (Hypericum perforatum).

HRT can affect the way some other medicines work:

• A medicine for epilepsy (lamotrigine), as this could increase frequency of seizures
• Medicines for Hepatitis C virus (HCV) (such as combination regimens ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin; glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir) may cause increases in liver function blood test results (increase in ALT liver enzyme) in women using CHCs containing ethinylestradiol. Evorel contains estradiol instead of ethinylestradiol. It is not known whether an increase in ALT liver enzyme can occur when using Evorel with this HCV combination regimen.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines including medicines obtained without a prescription, herbal medicines or other natural products. Your doctor will advise you.

Tell your doctor if you are going to have surgery. You may need to stop taking HRT about 4 to 6 weeks before the operation to reduce the risk of a blood clot. Your doctor will tell you when you can start taking HRT again.

If you visit a hospital or your family doctor for a blood or urine test, tell them that you are taking Evorel. This is because this medicine may affect the results of the tests.

Do not use this medicine if you are pregnant, think you may be pregnant or might become pregnant. This is because it may affect the baby.

If you become pregnant, contact your doctor straight away and remove the patch.

Do not use this medicine if you are breast-feeding.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Evorel is for use in postmenopausal women only. If you become pregnant, stop talking Evorel and contact your doctor.

There is no information about whether Evorel affects your ability to drive or use machines. See how this medicine affects you before you drive or use any tools or machines.

You may put an Evorel patch on at any time if:

• You have not used HRT before your menopause and no longer have menstrual periods
• Your menstrual cycles are not regular and you are not pregnant
• You are changing from HRT that does not give you a withdrawal bleed

Put an Evorel patch on within 5 days of the start of bleeding if:

• You are not currently using HRT and still having regular periods

Put an Evorel patch on at the end of a treatment cycle or one week after you finish using another HRT product if:

• You are changing from an HRT medicine that gives you a withdrawal bleed

If you are using another type of HRT:

• The day you start will depend on the type of HRT you have been using
• Talk to your doctor if you are not sure which type of HRT you are using

The patches need to be changed twice a week.

Start a new pack of Evorel as soon as you finish one. Do not leave a break between packs.

• You must change the patches twice a week to give your body a steady supply of hormones. There is enough hormone in each patch to last for several days
• Change your patch on the same two days every week. This will mean that one patch is on for three days and the next patch for four days
• For example, if you apply your first patch on a Monday, change it on Thursday and again on the following Monday. You can work out your two days from the following table, starting from the first day of use:

If you put your first patch on:

• Monday, Change on Thursday and Change again on Monday
• Tuesday, Change on Friday and Change again on Tuesday
• Wednesday, Change on Saturday and Change again on Wednesday
• Thursday, Change on Sunday and Change again on Thursday
• Friday, Change on Monday and Change again on Friday
• Saturday, Change on Tuesday and Change again on Saturday
• Sunday, Change on Wednesday and Change again on Sunday

To help you remember your two “patch change" days, mark them here or on the pack. They are written on the pack like this:

• Mon / Thur
• Tue / Fri
• Wed / Sat
• Thur / Sun
• Fri / Mon
• Sat / Tue
• Sun / Wed

Stick the patch onto a hairless area of skin below the waist. Most women prefer to wear the patch on the thigh or bottom.

• Do not apply on or near the breasts
• Do not put it on top of cuts, spots or anywhere the skin is irritated
• Do not use cream, moisturiser or talc before applying the patch
• Do not apply the patch on the same area of skin twice in a row
• It can be worn under loose areas of clothing
• Do not wear a patch under elasticated areas or a tight waistband
• Apply the patch to clean, dry, cool skin as soon as you open the protective pouch

Do not use a patch if its protective pouch is already open.

Step 1: Open and Peel

• Using the notches as a guide, tear along two edges of the pouch. Remove the patch
• With the protective backing facing you, bend and peel off half the backing. Don’t touch the sticky side - it may not stick properly

Step 2: Apply and Press

• Apply the open half of the patch to your skin
• Remove the remaining backing and press down the rest of the patch
• Warm and press the patch down to the skin with the palm of the hand for at least 10 seconds. Pressure and heat by the hand are crucial, to achieve maximum adhesion of the patch

• Peel an edge of the patch smoothly away from the skin
• Fold the patch in half, so that the sticky side sticks to itself
• Put it safely out of the reach of children and pets
• Do not flush used patches down the toilet

When you remove the patch some glue may remain on your skin. It will disappear with time, or you can use baby oil to remove it.

Apply a new patch but keep to your original ‘patch change’ days. If you have just had a bath or shower, wait until your skin cools before applying a new patch.

Talk to your doctor if you need more patches.

It is unlikely that you will have too much of the hormones in Evorel. The most common symptoms of having too much oestrogen in your body are:

• Tender or painful breasts
• Feeling sick (nausea) or being sick
• Unexpected vaginal bleeding
• Stomach pain or bloating

Removing the patch can reverse the effects of too much oestrogen. Talk to your doctor or pharmacist before using any more patches. Your doctor may decide to change the size of patch.

Change it as soon as you remember and then keep to your original ‘patch change’ days. You may get some bleeding and spotting like a period during this time.

The levels of hormone from the patches are too low to act as a contraceptive. Use non-hormonal contraceptive methods (such as a condom, diaphragm or coil) until your periods have completely stopped.

Everyday activities

• You can have a bath or shower as normal. Do not scrub too hard as this can loosen the edges of the patch
• You can go swimming. The patch will not be affected
• You can exercise and play sports. However, do not wear the patch under tight clothing or waist bands
• You can sunbathe. However, keep the patch covered, out of direct sunlight

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

If you are going to have surgery, tell the surgeon that you are using Evorel. You may need to stop using Evorel about 4 to 6 weeks before the operation to reduce the risk of a blood clot (see section 2, Blood clots in a vein). Ask your doctor when you can start using Evorel again.

If you have any further questions on the use of this medicine, ask your doctor.

• breast cancer;
• abnormal growth or cancer of the lining of the womb (endometrial hyperplasia or 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 over the age of 65;

For more information about these side effects, see Section 2.

• Sudden swelling of the face or throat which may cause difficulty in swallowing or breathing. This may be a sign of an allergic reaction. This only happens in a small number of people
• Blood clots (thrombosis), a heart attack or stroke
• Yellowing of the skin or whites of the eyes (jaundice), or other liver problems
• Migraine-type headaches for the first time or more frequent (affects less than 1 in 10 people)
• An increase in blood pressure
• Breast or ovarian cancer, endometrial cancer or hyperplasia (long, heavy or irregular vaginal bleeding)
• Convulsions or fits (frequency not known)

Very common (affects more than 1 in 10 people)

• Irritated, itchy skin and rash where the patch is applied

Common (affects less than 1 in 10 people)

• Red, puffy skin where the patch is applied
• Breast pain
• Rash or feeling itchy
• Feeling dizzy
• Feeling depressed
• Headache
• Feeling sick or having stomach pains
• Diarrhoea
• Pain, including pain in joints
• Break through bleeding, spotting or periods
• Weight gain

Uncommon (affects less than 1 in 100 people)

• Vaginal thrush
• Wind
• Being aware of your heart beat (palpitations)
• Fuller breasts
• Painful periods
• Swelling of hands and feet (peripheral oedema)
• Water retention or build-up of fluid under the skin (oedema)
• Muscle pain
• Allergic reactions (hypersensitivity)

Rare (affects less than 1 in 1,000 people)

• Bloated feeling
• Gallstones

Common (affects less than 1 in 10 people)

• Weight decrease
• Feeling sick

Uncommon (affects less than 1 in100 people)

• Problems with sight
• Indigestion
• Painful reddish skin nodules (erythema nodosum)
• Tender breasts

Rare (affects less than 1 in 1,000 people)

• Feeling anxious
• Increase or loss in sex drive
• Being sick
• Contact lenses may feel uncomfortable
• Excess hair growth
• Acne
• Muscle cramps
• Discharge from the vagina, premenstrual syndrome (PMS)
• Feeling tired

• Gall bladder disease
• Brown patches on your face or body, discoloration of the skin especially of the face or neck known as “pregnancy patches” (chloasma)
• Rash with target -shaped reddening or sores (erythema multiforme)
• Painful reddish skin nodules (erythema nodosum)
• Bruising on the legs
• Loss of memory (Dementia) (see section 2)

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard .

By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is estradiol

Evorel 25 contains 1.6 mg estradiol hemihydrate and delivers 25 micrograms of estradiol a day

Evorel 50 contains 3.2 mg estradiol hemihydrate and delivers 50 micrograms of estradiol a day

Evorel 75 contains 4.8 mg estradiol hemihydrate and delivers 75 micrograms of estradiol a day

Evorel 100 contains 6.4 mg estradiol hemihydrate and delivers 100 micrograms of estradiol a day

• The other ingredients are Duro-Tak 387-2287 (this makes the patches sticky), guar gum and Hostaphan MN19 (backing film).

Evorel comes in a memory pack containing eight patches.

Evorel 50 also comes in packs of twenty four patches.

Evorel 25 is marked CE25 and has a surface area of 8 sq cm

Evorel 50 is marked CE50 and has a surface area of 16 sq cm

Evorel 75 is marked CE75 and has a surface area of 24 sq cm

Evorel 100 is marked CE100 and has a surface area of 32 sq cm

The patches are square with rounded corners. They are clear with a sticky backing that can be stuck to the skin. Each patch comes in a protective sealed pouch.