PACKAGE LEAFLET INFORMATION FOR THE USER

Clinorette

17-fi estradiol

17-fi estradiol and norethisterone

In this leaflet

1.    What Clinorette is and what it is used for

2.    Before you take Clinorette

3.    How to take Clinorette

4.    Possible side effects

5.    How to store Clinorette

6.    Contents of the pack and other information

1.    WHAT CLINORETTE IS AND WHAT IT IS USED FOR

Clinorette Tablets is a hormone replacement therapy (HRT) in women who have not had their womb removed (a hysterectomy). It contains two types of female hormones, an oestrogen (17- fi estradiol)and a progestogen (norethisterone).

Clinorette is used for:

•    Relief of symptoms occuring 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"). Clinorette alleviates these symptoms after menopause. You will only be prescribed Clinorette if your symptoms seriously hinder your daily life. Clinorette Tablets contain norethisterone (a progesterone) to stop the endometrium from becoming too thick, and to make sure it is shed during the regular vaginal bleeds which go with this type of HRT.

•    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 Clinorette to prevent osteoporosis after menopause.

2.    BEFORE YOU TAKE CLINORETTE 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.

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 Clinorette 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 Clinorette.

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

Do not take Clinorette

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 Clinorette,

Do NOT take Clinorette Tablets if you:

•    are allergic to estradiol, norethisterone or any of the other ingredients of Clinorette (listed in section 6)

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

•    have cancer which is sensitive to oestrogens, such as cancer of the womb lining (endometrium), or if you are suspected of having it

•    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)

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

•    have a rare blood problem called "porphyria" which is passed down in families (inherited)

•    have or recently have had a disease caused by blood clots in the arteries, such as a heart attack, stroke or angina

•    have unexplained vaginal bleeding

•    have excessive thickening of the womb lining (endometrial hyperplasia) that is not been treated

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

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

When to take special care with Clinorette

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 Clinorette. If so, you should see your doctor more often for check-ups:

•    epilepsy

•    migraine or severe headaches

•    asthma

•    high blood pressure

•    increased risk of getting a oestrogen-sensitive cancer (such as having a mother, sister or grandmother who has had breast cancer - see Section 'Clinorette and cancer)

•    fibroids (growths inside your womb)

•    growth of womb lining outside your womb (endometriosis)

•    a history of excessive growth of the womb lining (endometrial hyperplasia)

•    gall stones

•    diabetes

•    a disease affecting the eardrum and hearing (otosclerosis)

•    a disease of the immune system that affects many organs of the body (systemic lupus erythematosus, SLE)

•    increased risk of developing blood clots (see "Blood clots in a vein (thrombosis)")

•    a liver disorder, such as a benign liver tumour

•    fluid retention due to cardiac or kidney problems

•    a very high level of fat in your blood (triglycerides)

Stop taking Clinorette and see a doctor immediately

If you notice any of the following when taking HRT:

• yellowing of your skin or the whites of your eyes (jaundice). These may be signs	• any of the conditions listed in the 'Do NOT take Clinorette' section.
of a liver disease	• signs of a blood clot, such as:
• a large rise in your blood pressure (symptoms may be headache, tiredness,	~ painful swelling and redness of the legs
dizziness)	~ sudden chest pain
• if you become pregnant	~ difficulty in breathing
• migraine-like headaches which happen for the first time	For more information, see 'Blood clots in a vein (thrombosis)'

Note: Clinorette 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 (norethisterone) in Clinorette protects you from this extra risk.

Unexpected bleeding

You will have a bleed once a month (so-called withdrawal bleed) while taking Clinorette. But, if you have unexpected bleeding or drops of blood (spotting) besides your monthly bleeding, which:

•    carries on for more than the first 6 months

•    starts after you have been taking Clinorette more than 6 months

•    carries on after you have stopped taking Clinorette 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.

How likely is breast cancer?

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:

•    dimpling of the skin

•    changes in the nipple

•    any lumps you can see or feel

Ovarian cancer

Ovarian cancer is rare. A slightly increased risk of ovarian cancer has been reported in women taking HRT for at least 5 to 10 years.

How likely is ovarian cancer?

Women aged 50 to 69 who are not taking HRT, on average about 2 women in 1000 will be diagnosed with ovarian cancer over a 5-year period. For women who have been taking HRT for 5 years, there will be between 2 and 3 cases per 1000 users (i.e. up to 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

•    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 Clinorette and see a doctor immediately".

How likely is a blood clot?

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.

Stroke

The risk of having a 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.

How likely is a stroke?

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 are worried about any of the above or if you have had a stroke in the past, speak to your doctor to see if you should take Clinorette Tablets.

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. Using other medicines

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

•    medicines for epilepsy (such as phenobarbital, phenytoin, carbamazepine)

•    medicines for tuberculosis ( such as rifampicin, rifabutin)

•    medicines for HIV infection (such as nevirapine, efavirenz, ritonavir, nelfinavir)

•    herbal remedies containing St John's Wort (Hypericum perforatum).

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.

Laboratory tests

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

Pregnancy and breast-feeding

Clinorette Tablets is for use in postmenopausal women only. If you become pregnant, stop taking Clinorette Tablets and contact your doctor.

Clinorette Tablets contain lactose

Lactose - If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

3. HOW TO TAKE CLINORETTE

Always follow your doctor's instructions completely and also follow any special instructions or warnings which appear on the label which the pharmacist has put on the package.

If you do not understand, or are in any doubt, ask your doctor or pharmacist. Your doctor will aim to prescribe the lowest dose to treat your symptom for as short as necessary. Speak to your doctor if you think this dose is too strong or not strong enough.

When to take the tablets

•    Clinorette tablets are provided in a calendar pack with 16 white tablets and 12 pink tablets arranged in a specific order.

•    One tablet is taken each day; a treatment cycle consists of 28 days.

•    Bleeding usually occurs after the last pink tablet of each pack.

•    It is important that you take the correct tablet each day. You should take the tablets at a regular time each day, either in the morning or in the evening.

•    The next pack is usually taken without a break in therapy.

If you have not been taking another type of HRT

•    If you are still having regular periods, you should tale your first white tablet on the fifth day of bleeding.

•    If you are not having regular periods you can start straight away.

•    If your doctor has given you other instructions, these should be followed precisely.

If you are changing from another type of HRT

•    If you are having periods, you should complete your current course of tablets and then take your first Clinorette tablet the    next day without a break    in treatment.

•    If you are not having periods, then you may start taking Clinorette tablets at any time according to any instructions given    to you by your doctor.

•    If your doctor has given you other instructions, these should be followed precisely.

If you need to have surgery

If    you are going to have surgery, tell the surgeon that you are taking Clinorette. You may need to stop taking Clinorette 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 Clinorette again.

If you take more Clinorette than you should

If you accidentally take too many tablets, you may experience nausea or vomiting. If you are worried or have any unusual symptoms you should contact your doctor. You should take your usual tablet the following day or follow the advice given to you by your doctor.

If you forget to take Clinorette

If you forget to take a dose, take a tablet as soon as you remember. If a whole day has passed, do not take two Clinorette tablets at the same time. Carry on taking one tablet a day until you have finished the 28 tablets in the pack and then carry on taking new packs of tablets as usual. You might notice some bleeding or spotting if you miss a tablet.

4. POSSIBLE SIDE EFFECTS

Like many medicines Clinorette can cause side effects, although not everybody gets them. Tell your doctor or pharmacist if you are worried about any side effects which you think may be due to Clinorette tablets.

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 2.

Serious side effects - see your doctor immediately

Tell your doctor immediately and STOP taking Clinorette if you experience any of the following:

•    jaundice (yellowing of the skin or eyes) or other liver problems

•    significantly increased blood pressure

•    pregnancy

•    signs of a blood clot in your leg or lungs e.g. painful swelling in your leg, sudden chest pain or difficulty breathing

•    signs of heart disease e.g. pain in your chest that spreads to your arm or neck which may be a heart attack

•    new or unusual migraine-type headaches, with or without disturbed vision

•    stroke

•    any changes in your breast such as dimpling of the skin, changes in the nipple or any lumps you can see or feel

•    breast cancer

•    endometrial cancer (cancer of the lining of the womb).

Other side effects In the reproductive and urinary system

•    breakthrough bleeding

•    spotting (bleeding from the vagina)

•    changes in menstrual blood flow

•    pain during your periods

•    symptoms similar to those felt just before a period

•    increase in the size of fibroids (growths in the womb)

•    vaginal thrush

•    changes in the neck of the womb (cervix)

•    symptoms like those of an infection of the bladder e.g. burning or itching on passing water.

In the breasts

•    tenderness

•    enlargement

•    secretion

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

5. HOW TO STORE CLINORETTE

Keep this medicine out of the sight and reach of children.

Do not take this medicine if the expiry date on the pack has passed. The expiry date refers to the last day of that month.

Clinorette should not be taken if the tablets show signs of deterioration such as discoloration.

Do not store above 25°C. Store in the original container or package in order to protect from light and moisture. Do not transfer the tablets to another container.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6. FURTHER INFORMATION What Clinorette Tablets contain

The active ingredients in Clinorette are 17-fi estradiol and norethisterone.

•    the white tablets contain 2mg of 17-fi estradiol

•    the pink tablets contain 2mg 17-fi estradiol and 1mg norethisterone.

Other ingredients are lactose (see end of Section 2 for further information on lactose), crospovidone, povidone, talc, magnesium stearate, Opandry white Y-I-7000 HSE (methocel E5, titanium dioxide E171, propylene glycol) and erythrosine lake HSE.

What Clinorette Tablets look like and contents of the pack

There are 16 round, white biconvex (curved on both sides) film coated tablets and 12 round, pink biconvex film coated tablets arranged in a specific order in each calendar blister pack. PVC and aluminium foil calendar blister pack enclosed in a cardboard carton. Each pack contains 28 tablets.

Marketing Authorisation Holder: ReSource Medical UK Ltd, 2 Carlton Avenue, Staincliff, Batley, WF17 7AQ, UK.

Manufacturer: Pharbil Waltrop GmbH, Im Wirringen 25, 45731 Waltrop, Germany.