XXXXXXXX

Package leaflet: Information for the user

Elleste Duet™ 1 mg Tablets

1    mg +1 mg/1 mg film-coated tablets

(estradiol + estradiol/norethisterone acetate) and

Elleste Duet™ 2 mg Tablets

2    mg + 2 mg/1 mg film-coated tablets

(estradiol + estradiol/norethisterone acetate)

i

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

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, please 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.

What is in this leaflet:

1.    What Elleste Duet is and what it is used for ------page 3

2.    What you need to know before you take Elleste Duet - - page 5

3.    How to take Elleste Duet------------page 24

4.    Possible side effects---------------page 30

5.    How to store Elleste Duet-------------page 35

6.    Contents of the pack and other information ------page 36

|1. WHAT ELLESTE DUET IS AND WHAT IT IS USED FOR

2

Elleste Duet is a Hormone Replacement Therapy (HRT). It contains two types of female hormones, an oestrogen (estradiol hemihydrate) 3

and a progestogen (norethisterone acetate).

Elleste Duet is used for:

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"). Elleste Duet alleviates these symptoms after menopause. You will only be prescribed Elleste Duet 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.

4

If you are at an increased risk of fractures due to osteoporosis and other medicines are not suitable for you, you can use Elleste Duet 2 mg to prevent osteoporosis after menopause.

2. WHAT YOU NEED TO KNOW BEFORE YOU TAKE ELLESTE DUET

Medical history and regular check-ups

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.

5

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

Do not take Elleste Duet

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 Elleste Duet.

Do not take Elleste Duet

1 If you have or have ever had breast cancer, or if you are suspected of having it

1 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

1 If you have any unexplained vaginal bleeding

1 If you have excessive thickening of the womb lining (endometrial hyperplasia) that is not being treated

■ If 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)

6

7

■    If you have a blood clotting disorder (such as protein C, protein S, or antithrombin deficiency)

■    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 or have ever had a liver disease and your liver function tests have not returned to normal

■    If you have a rare blood problem called “porphyria" which is passed down in families (inherited)

■    If you are allergic to estradiol hemihydrate or norethisterone acetate or any of the other ingredients of this medicine (listed in section 6)

If any of the above conditions appear for the first time while taking 8

Elleste Duet, stop taking it at once and consult your doctor immediately.

When to take special care with Elleste Duet

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 Elleste Duet. 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)

9

■    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

10

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 Stop taking Elleste Duet and see a doctor immediately

If you notice any of the following when taking HRT: any of the conditions mentioned in the ‘DO NOT take Elleste Duet' 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 11

■    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: Elleste Duet 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.

HRT and cancer

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 Elleste Duet protects you from this extra risk. Unexpected bleeding

12

You will have a bleed once a month (so-called withdrawal bleed) while taking Elleste Duet. But, if you have unexpected bleeding or drops of 13

blood (spotting) besides your monthly bleeding, which: carries on for more than the first 6 months ■ starts after you have been taking Elleste Duet more than 6 months carries on after you have stopped taking Elleste Duet see your doctor as soon as possible Breast cancer

Evidence suggests that taking combined oestrogen-progestogen and possibly also oestrogen-only HRT increases the risk of breast cancer. The extra risk depends on how long you take HRT. The additional risk becomes clear within a few years. However, it returns to normal within a few years (at most 5) after stopping treatment.

Compare

Women aged 50 to 79 who are not taking HRT, on average, 9 to 17 in 1000 will be diagnosed with breast cancer over a 5-year period. For women aged 50 to 79 who are taking oestrogen-progestogen HRT over 5 years, there will be 13 to 23 cases in 1000 users (i.e. an extra 4 to 6 cases).

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

1 dimpling of the skin 1 changes in the nipple 1 any lumps you can see or feel

14

15

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 is rare - much rarer than breast cancer. The use of oestrogen-only or combined oestrogen-progestagen HRT has been associated with a slightly increased risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women 16

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

17

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 taking Elleste Duet and see a doctor immediately". 18

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).

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.

19

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).

Underactive thyroid gland

If you are having medicine for treatment of an underactive thyroid 20

gland, your doctor will carry out tests while you are taking HRT, to ensure that your thyroid hormone levels remain acceptable.

Angioedema

If you have angioedema (a serious allergic reaction often involving swelling of the face, mouth and throat), oestrogens may make this worse.

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.

Children

Do not give this medicine to children.

21

1

Start Day

Elleste Duet™

Start Day

Elleste Duet™

MON

TUE

WED

THU

FRI

SAT

SUN

|

MON

TUE

WED

THU

FRI

SAT

SUN

TUE

WED

THU

FRI

SAT

SUN

MON

TUE

WED

THU

FRI

SAT

SUN

MON

WED

THU

FRI

SAT

SUN

MON

TUE

1

WED

THU

FRI

SAT

SUN

MON

TUE

THU

FRI

SAT

SUN

MON

TUE

WED

1

THU

FRI

SAT

SUN

MON

TUE

WED

FRI

SAT

SUN

MON

TUE

WED

THU

1

FRI

SAT

SUN

MON

TUE

WED

THU

SAT

SUN

MON

TUE

WED

THU

FRI

1

SAT

SUN

MON

TUE

WED

THU

FRI

SUN

MON

TUE

WED

THU

FRI

SAT

SUN

MON

TUE

WED

THU

FRI

SAT

_J

I

K.

40

1

_1_

41

Start Day

t

MON TUE

WED

THU

Elleste Duet™

FRI SAT SUN

TUE

WED

THU

FRI

SAT

SUN

MON

WED

THU

FRI

SAT

SUN

MON

TUE

THU

FRI

SAT

SUN

MON

TUE

WED

FRI

SAT

SUN

MON

TUE

WED

THU

SAT

SUN

MON

TUE

WED

THU

FRI

SUN

MON

TUE

WED

THU

FRI

SAT