Evorel Conti Leaflet

PACKAGE LEAFLET: INFORMATION FOR THE USER

Evorel® Conti

Estradiol hemihydrate, norethisterone acetate

Evorel is a registered trademark

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read itagain

• If you have any further questions, ask your doctor orpharmacist

• 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. Thisincludes any possible side effects not listed in this leaflet. See section 5.

What is in this leaflet

• What Evorel Conti is and what it is used for

• What you need to know before you use Evorel Conti

• Safety of HRT

• How to use Evorel Conti

• Possible side effects

• How to store Evorel Conti

• Contents of the pack and other information

What Evorel Conti is and what it is used for

The name of your medicine is Evorel Conti. It belongs to a group of medicines called hormone replacement therapy (HRT).

Evorel Conti contains two medicines:

• An oestrogen (estradiol)

• A progestogen (norethisterone) They are both female hormones.

Evorel Conti comes in a ‘memory pack’. This can be used to help you remember when to change your patches. Each pack contains eight or twenty-four patches.

The hormones are spread evenly in each patch. They pass slowly into your body through the skin.

What Evorel Conti is used for

Evorel Conti is used:

• For 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

• To prevent osteoporosis (fragile bones) in women who have had the menopause and are most likely to have bone problems. Evorel Conti is only used if other medicines for osteoporosis have been tried first and they have not worked
  

What is the menopause?

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.

How Evorel Conti works

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.

What you need to know before you use Evorel Conti

Do not use Evorel Conti if:

• You are allergic to anything in the patches (listed in section 7)

• You have (or have ever had), or think you may have, breast cancer

• You have (or are suspected of having) or ever had a cancer that was made worse by oestrogens (such as endometrial cancer)

• You have a thickening of the lining of the womb (endometrial hyperplasia) which has not been treated

• You have vaginal bleeding you cannot explain

• You have ever had blood clots in a vein (thrombosis), such as in the legs (deep vein thrombosis) or a blood clot that has travelled to your lung (pulmonary embolism)

• You have problems with your blood which increases the likelihood of developing a blood clot (thrombosis) (such as protein C, protein S or antithrombin deficiency)

• You have (or have ever had) a liver disease and your liver functiontests have not returned to normal
  

• You have ever had blocked arteries (arterial thrombo-embolic disease) that gave you angina or a heart attack resulted in a stroke

• You have a blood problem called ‘porphyria’

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.

Stop using Evorel Conti at once if any of the above appears for the first time and talk to your doctor immediately.

Evorel Conti should not be used by children.

Medical check-ups

Before taking HRT, your doctor should ask about you and your family’s medical history. Your doctor may decide to examine your breasts or your tummy, and may do an internal examination. They will only do this if it is necessary for you, or if you have any special concerns.

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

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

Tell your doctor if you have ever had any of the following. You may need these checks more often.

• A problem caused by growth of the womb lining:

  • Inside the womb (fibroids)

  • Outside the womb (endometriosis)

  • Thickening of the lining of the womb (endometrial hyperplasia)

• Increased risk of blood clots (see ‘Blood clots’ in section 3 below)

• A family history of increased risk of cancers related to oestrogens (see ‘Breast cancer’ in section 3 below) such as having a mother, sister or grandmother who has had breast cancer

• High blood pressure (hypertension). Your doctor may tell you to stop using Evorel Conti if your blood pressure goes up

• Diabetes

• Gallstones

• Migraine or severe headaches

• Systemic lupus erythematosus (SLE). This is an allergic condition that causes joint pain, skin rashes and fever

• Epilepsy

• Asthma

• A disease affecting the eardrum and hearing(otosclerosis)

• A liver disorder, such as a benign liver tumour

• Fluid retention due to heart or kidney problems

• High levels of fat (triglycerides) in your blood as you may have a higher risk of pancreatitis (inflammation of the pancreas, which causes severe pain in the abdomen and back)
  

• Any breast problems

• 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.

Stop using Evorel Conti and see a doctor immediately

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

• 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)

Other medicines and Evorel Conti

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines that you buy without a prescription or herbal medicines.

In particular, tell your doctor or pharmacist if you are taking any of the following:

• Medicines for epilepsy such as phenobarbital, phenytoin or carbamazepine

• Medicines for tuberculosis such as rifampicin or rifabutin,

• Medicines for HIV infection, such as nevirapine, efavirenz, ritonavir and nelfinavir

• Medicine for Hepatitis C infection, telaprevir

• Bosentan – for high blood pressure in the blood vessels of thelungs

• St. John’s Wort – for depression

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

• A medicine for epilepsy called lamotrigine. Using Evorel Conti with lamotrigine could affect control of your epilepsy

Operations or tests

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 Conti. This is because this medicine may affect the results of the tests.

Pregnancy and breast-feeding

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

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.

Driving or using machines

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.

Safety of HRT

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

Effect of HRT on heart and circulation

Heart disease (heart attack)

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.

HRT will not help to prevent heart disease.

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.

If you get a pain in your chest that spreads to your arm and neck

• See a doctor as soon as possible

• Do not take any more HRT until your doctor says you can This pain may be a sign of heart disease.

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.

How likely is a 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.

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.

Blood clots in a vein (thrombosis)

HRT may increase the risk of blood clots in the veins (also called deep vein thrombosis, or DVT). 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.

These blood clots are not always serious. However, if a clot travels to the lungs, it can cause chest pain, breathlessness, collapse or even death. This is called pulmonary embolism, or PE.

You are more likely to get a blood clot if:

• You are very overweight (BMI above 30 kg/m2)

• You are getting older

• You have had a blood clot before

• You are taking medicine containing an oestrogen

• You have cancer

• Any of your close family have had blood clots

• You are pregnant or have just had a baby

• You have had one or more miscarriages

• You have any blood clotting problem that needs treatment with a medicine such as warfarin

• You are off your feet for a long time because of major surgery, injury or illness

• You are going on a long journey and will not be moving about for some time

• You have a rare illness called SLE (Systemic lupus erythematosus)

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

How likely is a blood clot?

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.

HRT and Cancer

Breast cancer

Women who have breast cancer, or have had breast cancer in the past, should not take HRT.

Taking HRT slightly increases the risk of breast cancer. The risk is also slightly increased if you have a later menopause.

• Postmenopausal women taking oestrogen-only HRT for 5 years – the risk is about the same as for a woman of the same age who is still having periods over that time, and not taking HRT

• Women taking oestrogen plus progestogen HRT – the risk is higher than for oestrogen-only HRT. However, oestrogen plus progestogen HRT is beneficial for the endometrium (see ‘Endometrial cancer’)

For all kinds of HRT, the extra risk of breast cancer goes up the longer you take it. However, it returns to normal within about 5 years after stopping HRT.

Your risk of breast cancer is also higher if:

• You have a close relative (mother, sister or grandmother) who has had breast cancer

• You are very overweight

How likely is breast cancer?

Looking at women aged 50 to 79, on average, over the next 5 years:

• In women not taking combined HRT between 9 and 17 in 1000 will get breast cancer

• In women taking oestrogen-progestogen HRT at age 50 to 79 and take it for 5 years, between 13 and 23 in 1000 will get breast cancer (an extra 4-6 cases)

If you notice any changes in your breast, 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 mammography 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.

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

Taking oestrogen-only HRT for a long time can increase the risk of cancer of the lining of the womb (the endometrium). Taking a progestogen as well as the oestrogen helps to lower the extra risk.

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.

How likely is endometrial cancer?

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 in1000 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.

If you get breakthrough bleeding or spotting, it is usually nothing to worry about, especially during the first few months of taking HRT.

But if the bleeding or spotting:

• Carries on for more than the first few months

• Starts after you have been on HRT for a while

• Carries on even after you’ve stopped taking HRT

Make an appointment to see your doctor as soon as possible. It could be a sign that your endometrium has become thicker.

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).

Dementia

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

How to use Evorel Conti

Always use Evorel Conti exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure. Your doctor will aim to reduce your symptoms with the lowest possible dose for the shortest amount of time.

When to start using Evorel Conti

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.

Using the patches

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.

Changing your patches

• 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:

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

Where to apply the patch

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

Putting a patch on

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

• Press the patch with the palm of your hand to make sure it is firmly stuck
  

Removing a 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 in with the household rubbish, 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.

If a patch falls off

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

Talk to your doctor if you need more patches.

If you forget to change the 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.

If you use more Evorel Conti than you should

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 and/or progestogen. Talk to your doctor or pharmacist before using any more patches.

Contraception while using Evorel Conti

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.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following diseases are reported more often in women using HRT compared to women not using HRT:

• 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 3.

Take off the patch and tell your doctor straight away if you notice or suspect any of the following. You may need urgent medical treatment.

• 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)

Tell your doctor if you notice any of the following side effects while using Evorel Conti:

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 (hypersensitvity)

• 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)

• Diarrhoea

• 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

The following side effects have been reported with other combined HRTs:

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 discolouration

• 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

The following side effects have been reported in association with oestrogen/progestogen treatment

• Gall bladder disease

• Brown patches on your face or body (chloasma)

• Rash with painful reddish skin nodules(eythema 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

Reporting of side effects

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.

How to store Evorel Conti

Keep this medicine out of the sight and reach of children. It should be stored at room temperature (at or below 25°C). Keep in the original pouch and carton.

Do not use Evorel Conti after the expiry date which is stated on the label. The expiry date refers to the last day of that month.

Do not use a patch if the protective pouch is open.

Contents of the pack and other information

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).

What Evorel Conti looks like and contents of the pack

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.

The product licence is held by:

Theramex HQ UK LTD, Sloane Square House, 1 Holbein Place, London SW1W 8NS, UK

Evorel Conti is made by:

Aesica Pharmaceuticals GmbH Alfred-Nobel-Str. 10

40789 Monheim am Rhein Germany

For information in large print, tape, CD or Braille, telephone 0800 198 5000.

This leaflet was last revised in November 2019.