Document: leaflet MAH BRAND_PL 03132-0125 change

• leaflet MAH BRAND_PL 03132-0125
• leaflet MAH BRAND_PLPI 13826-1141

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Package leaflet:

Information for the user

Kliovance®

1 mg/0.5 mg film-coated tablets

Estradiol/norethisterone acetate

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, 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

8-2901-01-053-9 includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.    What Kliovance® is and what it is used for

2.    What you need to know before you take Kliovance®

3.    How to take Kliovance®

4.    Possible side effects

5.    How to store Kliovance®

6.    Contents of the pack and other information

1. What Kliovance® is and what it is used for

Kliovance® is a continuous combined Hormone Replacement Therapy (HRT). It contains two types of female hormones, an oestrogen and a progestagen. Kliovance® is used in postmenopausal women with at least 1 year since their last natural period.

Kliovance® is used for:

Relief of symptoms occurring after menopause

During the menopause, the amount of oestrogen produced by a woman's body drops. This can cause symptoms such as hot face, neck and chest ('hot flushes'). Kliovance® alleviates these symptoms after menopause. You will only be prescribed Kliovance® 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 Kliovance® to prevent osteoporosis after menopause.

Kliovance® is prescribed for women who have not had their womb removed, and whose periods stopped more than a year ago. There is only limited experience of treating women older than 65 years with Kliovance®.

2. What you need to know before you take Kliovance® 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 Kliovance® 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 Kliovance®. Go for regular breast screening, as recommended by your doctor.

Do not take Kliovance®

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 Kliovance®.

Do not take Kliovance®:

•    If you have, have had or suspect having breast cancer.

•    If you have, or have had 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 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).

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

•    If you have or previously 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 (hypersensitive) to estradiol, norethisterone acetate or any of the other ingredients of Kliovance® (listed in section 6 'Contents of the pack and other information').

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

Warnings and precautions

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 Kliovance®.

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

•    fibroids inside your womb

•    growth of the 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

a 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

•    lactose intolerance.

Stop taking Kliovance® 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 Kliovance®' 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)'.

Note: Kl iovance® 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 progestagen in Kliovance® 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 Kliovance®. However, if the irregular bleeding:

•    carries on for more than the first 6 months

•    starts after you have been taking Kliovance® for more than

6 months

•    carries on after you have stopped taking Kliovance®

see your doctor as soon as possible. Breast cancer

Evidence suggests that taking combined oestrogen-progestagen 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 1,000 will be diagnosed with breast cancer over a 5-year period. For women aged 50 to 79 who are taking oestrogen-progestagen HRT over 5 years, there will be 13 to 23 cases in 1,000 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. 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. A slightly increased risk of ovarian cancer has been reported in women taking HRT for at least 5 to 10 years. Women aged 50 to 69 who are not taking HRT, on average, about 2 women in 1,000 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 1,000 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 Kliovance® 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 1,000 would be expected to get a blood clot in a vein.

For women in their 50s who have been taking oestrogen-progestagen HRT for over 5 years, there will be 9 to 12 cases in 1,000 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-progestagen HRT are slightly more likely to develop heart

disease than those not taking any HRT.

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 1,000 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 1,000 users over 5 years (i.e. an extra 3 cases).

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 Kliovance®. This might lead to irregular bleeding. This applies to the following medicines:

•    Medicines for epilepsy (such as phenobarbital, phenytoin and carbamazepine)

•    Medicines for tuberculosis (such as rifampicin and rifabutin)

•    Medicines for HIV infections (such as nevirapine, efavirenz, ritonavir and nelfinavir)

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

•    Medicines for hepatitis C infections (such as telaprevir).

Other medicines may increase the effects of Kliovance®:

•    Medicines containing ketoconazole (a fungicide).

Kliovance® may have an impact on a concomitant treatment with cyclosporine.

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 Kliovance®, because this medicine can affect the results of some tests.

Taking Kliovance® with food and drink

The tablets can be taken with or without food and drink.

Pregnancy and breast-feeding Pregnancy: Kliovance® is for use in postmenopausal women only. If you become pregnant, stop taking Kliovance® and contact your doctor.

Breast-feeding: You should not take Kliovance® if you are breastfeeding.

Driving and using machines

Kliovance® has no known effect on the ability to drive or use machines.

Important information about some of the ingredients in Kliovance®:

Kliovance® contains lactose monohydrate. If you have an intolerance to some sugars, contact your doctor before taking Kliovance®.

3. How to take Kliovance®

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are unsure.

Take one tablet once a day, at about the same time each day.

Once you have finished all the 28 tablets in the pack, start a new pack continuing the treatment without interruption.

For further information on the use of the calendar pack, see 'User Instructions' at the end of the package leaflet.

You may start treatment with Kliovance® on any convenient day. However, if you are switching from an HRT product when you have monthly bleeding, start your treatment straight after the bleeding has ended.

Your doctor should 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.

If you take more Kliovance® than you should

If you have taken more Kliovance® than you should, talk to a doctor or pharmacist. An overdose of Kliovance® could make you feel sick or vomit.

If you forget to take Kliovance®

If you forget to take your tablet at the usual time, take it within the next 12 hours. If more than 12 hours have gone by, skip the missed dose and start again as