Evorel Conti

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

• The symptoms of the menopause (see ‘What is the menopause?’). It is suitable for women who have not had a period (menstrual bleed) for at least 18 months
• Prevent osteoporosis (fragile bones) in women who have had the menopause and are most likely to have bone problems. Evorel Conti 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.

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 Conti alleviates these symptoms after menopause. You will only be prescribed Evorel Conti if your symptoms seriously hinder your daily life.

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 Conti to prevent osteoporosis after menopause.

Evorel Conti is known as ‘continuous combined’ HRT. This is because both hormones in the patch are released all the time.

Evorel Conti 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

Most women do not have a regular monthly period with Evorel Conti. However, bleeding or spotting does often occur in the first few months until treatment settles down.

Evorel Conti 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.

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 Conti 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 Conti.

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

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

Do not use this medicine if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before using Evorel Conti.

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

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 Conti. 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 tumour;
• 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;
• Thyroid problems;
• History of sudden swelling of the face or throat, which may cause difficulty in swallowing or breathing, rapid swelling of the hands and feet and, stomach cramps.

You may still be able to use Evorel Conti, but you should discuss this with your doctor first. Also tell your doctor if these illnesses return or get worse while you are using Evorel Conti.

If you have had a premature menopause the risk of using HRT may be different. Talk to your doctor about the risks.

• 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 using Evorel Conti

• any of the conditions mentioned in the ‘DO NOT use Evorel Conti’ 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 Conti 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).

The progestogen in Evorel Conti protects you from this extra risk.

Irregular bleeding

You may have irregular bleeding or drops of blood (spotting) during the first 3-6 months of taking Evorel Conti. However, if the irregular bleeding:

• carries on for more than the first 6 months;
• starts after you have been taking Evorel Conti for more than 6 months;
• carries on after you have stopped taking Evorel Conti;

see your doctor as soon as possible.

If you still have your womb, your doctor will usually prescribe a progestogen as well as oestrogen. These may be prescribed separately, or as a combined HRT product.

If you have had your womb removed (a hysterectomy), your doctor will discuss with you whether you can safely take oestrogen without a progestogen.

If you have had your womb removed because of endometriosis, any endometrium left in your body may be at risk of cancer. This means your doctor may prescribe HRT that includes a progestogen as well as an oestrogen.

Your product, Evorel Conti, contains a progestogen.

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Looking at women aged 50 to 65 who still have a womb, on average:

• In women not taking HRT - 5 in 1000 will get endometrial cancer
• In women taking oestrogen-only HRT- between 10 and 60 in 1000 will get endometrial cancer, (i.e. between 5 and 55 extra cases) depending on the dose and how long you take it for.

The addition of a progestogen to oestrogen-only HRT substantially reduces the risk of endometrial cancer.

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.

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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).

Effect of HRT on heart and circulation

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;
• You have a rare illness called SLE (Systemic lupus erythematosus);
• You have cancer;
• You are taking medicine containing an oestrogen.

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

If any of these things apply to you, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s, on average, over 5 years:

• In women not taking HRT – between 4 and 7 in 1000 would be expected to get a blood clot
• In women taking oestrogen-progestogen HRT - 9 and 12 in 1000 would be expected to get a blood clot (an extra 5 cases)

If you get painful swelling in your leg, sudden chest pain or have difficulty breathing

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

These may be signs of a blood clot.

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.

HRT is not recommended for women who have had heart disease recently. If you have ever had heart disease, talk to your doctor to see if you should be taking HRT.

Stroke

Research suggests that HRT slightly increases the risk of having a stroke. Other things that can increase the risk of stroke include:

• Getting older
• High blood pressure
• Smoking
• Drinking too much alcohol
• An irregular heartbeat

If you are worried about any of these things, or if you have had a stroke in the past, talk to your doctor to see if you should take HRT.

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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.

Looking at women in their 50s, on average, over 5 years:

• In women not taking HRT - 8 in 1000 would be expected to have a stroke
• In women taking HRT - 11 in 1000 would be expected to have a stroke (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

• HRT will not prevent memory loss. There is some evidence of a higher risk of memory loss in women who start using HRT after the age of 65. Speak to your doctor for advice;
• 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).

Evorel Conti should not be used by children.

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

• Medicines for epilepsy (such as phenobarbital, phenytoin or carbamazepine);
• Medicines for tuberculosis (such as rifampicin, rifabutin);
• Medicines for HIV infection (such us nevirapine, efavirenz, ritonavir or nelfinavir);
• Medicine for Hepatis C infection, telaprevir;
• Bosentan - for high blood pressure in the blood vessels of the lungs;
• Herbal remedies containing St John’s Wort (Hypericum perforatum).

Taking these medicines with Evorel Conti can stop it from working as well. Because of this you may get some bleeding, like a period, when you are not expecting it.

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 Conti contains estradiol instead of ethinylestradiol. It is not known whether an increase in ALT liver enzyme can occur when using Evorel Conti 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.

If you need a blood test, tell your doctor or the laboratory staff that you are taking Evorel Conti, because this medicine can affect the results of some tests.

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 Conti. 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.

Evorel Conti is for use in postmenopausal women only. If you become pregnant, remove the patch and contact your doctor.

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

Ask your doctor or pharmacist for advice before taking any medicine if you are pregnant or breast-feeding.

There is no information about whether Evorel Conti 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 Conti patch on at any time if:

• You have not been using another type of HRT

Put an Evorel Conti 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 Conti 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:

• 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 if you do

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.

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.

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

• Tender breasts
• Feeling sick (nausea) or being sick
• Unexpected vaginal bleeding
• Feeling depressed
• Tiredness
• Acne
• Growth of body or facial hair

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

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 taking Evorel Conti. You may need to stop taking Evorel Conti 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 taking Evorel Conti again.

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

• Sudden swelling of the face or throat which may cause difficulty in swallowing or breathing, rapid swelling of the hands and feet and stomach cramps
• Blood clots (thrombosis) (affects less than 1 in 1000 people) or stroke (frequency not known)
• 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 100 people)
• An increase in blood pressure (affects less than 1 in 10 people)
• Breast or ovarian cancer, endometrial cancer or hyperplasia (long, heavy or irregular periods)
• Widespread rash with peeling skin and blistering in the mouth, eyes and genitals (Stevens-Johnson syndrome) (frequency not known)
• Convulsions or fits (affects less than 1 in 1,000 people)

Very common (affects more than 1 in 10 people)

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

Common (affects less than 1 in 10 people)

• Allergic reaction (hypersensitivity)
• Being unable to sleep
• Feeling depressed, nervous or anxious
• Headache
• Being aware of your heartbeat (palpitations)
• Varicose veins
• Flushing, skin reddening
• Breast pain
• Numb or tingling hands or feet
• Feeling sick (nausea)
• Diarrhea
• Stomach ache
• Pain including pain in the back or joints
• Painful periods
• Discharge from the vagina
• Irregular, heavy or prolonged bleeding from the vagina, including after sex
• Water retention or build-up of fluid under the skin (oedema)
• Feeling tired
• Weight gain

Uncommon (affects less than 1 in 100 people)

• Vaginal infections such as thrush
• Less interest in sex than usual
• Wind
• Itchy skin
• Rash
• Swelling of the hands and feet (peripheral oedema)
• Muscle pain

Frequency not known

• Mood swings
• Feeling dizzy
• Bloated feeling
• Gallstones
• Fuller breasts

Very common (affects more than 1 in 10 people)

• Tender breasts

Common (affects less than 1 in 10 people)

• Mood changes
• Indigestion
• Acne
• Dry skin
• Pain in extremity (e.g. back pain, arms, legs, wrists, ankles)
• Severe contractions of the uterus
• Vaginal infection (white or yellowish discharge from the vagina)

Uncommon (affects less than 1 in100 people)

• Dizziness
• Being sick
• Skin discoloration
• Abnormal liver function tests

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

• Gallstones
• Muscle weakness
• Benign growths in the uterus smooth muscle
• Cysts close to the fallopian tube

Very Rare (affects less than 1 in 10,000 people)

• Yellowing of the skin, itching, dark coloured urine

Frequency not known

• Hair loss

• Gall bladder disease
• Various skin disorders:
  • discoloration of the skin especially of the face or neck known as “pregnancy patches” (chloasma);
  • painful reddish skin nodules (erythema nodosum)
  • rash with target shaped reddening or sores (erythema multiforme)
• Rash with red or purple coloured spots (vascular purpura)
• Loss of memory (Dementia) (see section 2)
• Dry eyes
• Change to composition of tears

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 substances in Evorel Conti are estradiol hemihydrate and norethisterone acetate.

Each Evorel Conti patch contains 3.2 mg of estradiol hemihydrate and 11.2 mg of norethisterone acetate. Each Evorel Conti patch delivers 50 micrograms of estradiol and 170 micrograms of norethisterone acetate a day.

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

Evorel Conti comes in a memory pack containing eight or twenty-four patches (marked CEN1).

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 and has a surface area of 16 sq cm.