Package Leaflet: information for the user

Tibolone 2.5 mg tablets

Tibolone

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, pharmacist or nurse.

•    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 of the side effects talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.    What Tibolone Tablets is and what it is used for

2.    What you need to know before you take Tibolone Tablets

3.    How to take Tibolone Tablets

4.    Possible side effects

5.    How to store Tibolone Tablets

6.    Contents of the pack and other information

1. What Tibolone Tablets is and what it is used for

Tibolone Tablets is a Hormone Replacement Therapy (HRT). It contains tibolone, which is the active substance that has beneficial effects on the different organ tissues in the body such as the bones, brain and vagina. Tibolone Tablets is used in post-menopausal women with at least 12 months (1 year) since their last natural period.

Relief of symptoms occurring after menopause

During your menopause, the amount of oestrogen produced by a woman’s body is reduced. This can cause symptoms such as a hot face, neck and chest (“hot flushes”). Tibolone Tablets alleviates these symptoms after menopause. You will only be prescribed this medicine if your symptoms seriously hinder your daily life. Prevention of osteoporosis

After your menopause, some women may develop fragile bones (osteoporosis). You should discuss all available options with your doctor.

If your doctor has told you that you have a high risk of developing fractures due to a medical condition known as osteoporosis, and other medicines are not suitable for you, you can start to use Tibolone Tablets to prevent this condition after your menopause. There are three kinds of Hormone Replacement Therapy being used:

•    Oestrogen-only HRT

•    Combined HRT, containing two kinds of female hormones, known as oestrogen and a progestogen.

Tibolone Tablets, which contains the active substance called Tibolone.

Tibolone is different from how the other types of hormone replacement therapy works, such that, instead of the actual hormones (such as oestrogen and progestogen), this medicine contains the active substance, tibolone. Your body will break down tibolone to produce the natural hormones. Its beneficial effects are similar to that used in combined HRT.

2. What you need to know before you take Tibolone Tablets

Medical History and regular check-ups

The use of HRT or Tibolone Tablets carries some risks that need to be considered when deciding whether to start taking the medicine, or whether it’s appropriate to continue taking it. This is particularly important if you are older than 60 years of age.

Clinical experience is limited in treating women with a premature menopause (due to ovarian failure or surgery). If you have a premature menopause the risks of using HRT or Tibolone Tablets may be different. Please talk to your doctor for advice.

Before you start taking (or restart) HRT or Tibolone Tablets Your doctor will talk to you about your medical concerns and any related family 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.

Tell your doctor if you have any medical problems or illnesses.

Regular check-ups

Once you have started on Tibolone Tablets, you should see your doctor for regular check-ups (at least once a year). At these checkups, discuss with your doctor the benefits and risks of continuing with Tibolone Tablets.

It is necessary for you to attend appointments for regular breast screening and have cervical smear tests as recommended by your doctor. Check your breasts regularly for any changes, such as dimpling of the skin, changes in the nipple or any lumps you can see or feel.

Do not take Tibolone Tablets

If any of the following applies to you, do not take this medicine. If you are not sure about any of the points below, talk to your doctor before taking this medicine. Do not take this medicine if:

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

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

•    you have any unexplained vaginal bleeding

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

•    you have or previously had a blood clot in a vein (thrombosis), such as in your legs (deep venous thrombosis) or in the lungs (pulmonary embolism)

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

•    you have or previously had a disease caused by a blood clot in the arteries, such as a heart attack, stroke or angina

•    you have or previously had a liver disease and your liver function tests have not returned to normal

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

•    you are allergic to tibolone or any of the other ingredients of this medicine (listed in section 6)

•    you are pregnant or think you might be pregnant

•    you are breastfeeding

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

If you have started your menopause you should not take Tibolone Tablets until 12 months have lapsed since your last natural period. If you take it sooner, this may cause irregular vaginal bleeding.

Warnings and precautions

Talk to your doctor or pharmacist before taking Tibolone Tablets. Before you start treatment with Tibolone Tablets, tell your doctor if you have, or previously had any of the following medical problems, as these may return or become worse during treatment with this medicine. If this is the case, you should see your doctor more often for regular 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)

•    high risk of developing blood clots. See section “Blood clots in a vein (thrombosis)”

•    high risk of getting an oestrogen-sensitive cancer (such as having a mother, sister or grandmother who previously had breast cancer)

•    high blood pressure

•    liver disorder, such as a benign liver tumour

•    diabetes

•    gallstones

•    migraine or severe headaches

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

•    epilepsy

•    asthma

•    disease affecting the ear drum and hearing (otosclerosis)

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

•    fluid retention due to cardiac or kidney problems

Stop taking Tibolone Tablets and see your doctor immediately If you notice any of the following when taking Tibolone Tablets:

•    any of the conditions mentioned in section “Do not take Tibolone Tablets”

•    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 associated with headache, tiredness and/or dizziness)

•    migraine-like headaches which occur for the first time

•    if you become pregnant

•    if you notice any signs of a blood clot, such as:

-    a painful swelling and redness of the legs

-    a sudden pain in the chest

-    difficulties in breathing

For more information, see details in section “Blood clots in a vein (thrombosis)”.

Note: Tibolone Tablets 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)

There have been reports of increased cell growth or cancer forming in the lining of the womb in women when using Tibolone Tablets. The longer you use this medicine, the greater the risk of developing a cancer in the lining of the womb.

Irregular bleeding

You may have irregular bleeding or drops of blood (spotting) during the first 3-6 months of taking Tibolone Tablets. See your doctor as soon as possible if the bleeding or spotting:

•    Carries on for more than the first 6 months

•    Starts after you have been taking Tibolone Tablets for more than 6 months

•    Carries on even after you’ve stopped taking Tibolone Tablets Breast Cancer

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

Compare

Studies have revealed that women taking Tibolone Tablets have a lower risk of developing breast cancer than women using combined HRT and a comparable risk is demonstrated with oestrogen-only HRT.

It is necessary to regularly check your breasts. See your doctor as soon as possible if you notice any changes developing in your breasts, such as:

•    Dimpling or sinking of the skin

•    Changes in the nipple

•    Any lumps you can see or feel 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 aged 50 to 54 who are not taking HRT, on average about 2 in 1,000 women 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 2,000 users (i.e. about 1 extra case).

With the use of Tibolone Tablets, the increased risk of developing ovarian cancer is similar as with the other types of HRT.

The effects of HRT on the 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 your treatment.

Blood clots can be serious, and if one travels to the lungs, it can cause chest pains, feelings of breathlessness, fainting or even death. You are more likely to get a blood clot in your veins as you get older. If any of the following points below apply to you, let your doctor know if:

•    you are pregnant or recently had a baby

•    you use oestrogens

•    you are unable to walk for a long time because of a major surgery, injury or illness (see also section 2, If you need to have surgery)

•    you are seriously overweight (BMI >30 kg/m²)

•    you have any blood clotting problems that need long-term treatment with a medicine used to prevent blood clots

•    any of your close relatives has ever had a blood clot in the leg, lung or in another organ

•    you have systemic lupus erythematosus (SLE)

•    you have cancer

For signs of a blood clot, see section “Stop taking Tibolone Tablets and see your doctor immediately”.

Compare

Studies have revealed that women in their 50s who are not taking HRT, on average over a 5-year period, 4 to 7 in 1,000 women 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 1,000 users (i.e. an additional 5 cases).

With the use of Tibolone Tablets, the increased risk of getting a blood clot in a vein is lower than with other types of HRT.

Heart disease (heart attack)

There is no evidence that HRT or Tibolone Tablets will prevent a heart attack.

Women over the age of 60 who use oestrogen-progestogen HRT are slightly more likely to develop heart disease than those not taking any HRT. As the risk of heart disease is strongly dependant on the age of the patient, the number of extra cases of developing heart disease with the use of oestrogen-progesterone HRT is very low in healthy women close to menopause, but the risk will rise with more advanced age.

There is no evidence to suggest that the risk of myocardial infarction with Tibolone Tablets is different to the risks associated with other types of HRT.

Stroke

Recent research suggests that with the use of HRT and Tibolone Tablets, a slight tendency of getting stroke has been demonstrated. The increased risk is generally seen mainly in women who are over the age of 60 years. Other factors that can increase the risk of getting a stroke include:

-    Getting older

-    High blood pressure

-    Smoking

-    Drinking too much alcohol

-    An irregular heart beat

If you are concerned about any of the points discussed above, please talk to your doctor to see if you should take this medicine.

Compare

Studies have revealed that women in their 50s who are not taking tibolone, on average over a 5-year period, 3 women in 1,000 would be expected to have a stroke. For women in their 50s who are taking tibolone, the figure would be 7 in 1,000 (i.e. an additional 4 cases).

However, women in their 60s who are not taking tibolone, on average over a 5-year period, 11 in 1,000 women would be expected to have a stroke.

For women in their 60s who are taking tibolone, the figure would be 24 in 1,000 (i.e. an additional of 13 cases).

Other conditions and Tibolone Tablets

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.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Tibolone Tablets is not intended for contraceptive use.

Treatment with Tibolone Tablets results in a marked dose-dependent decrease in HDL cholesterol (from -16.7% with a 1.25 mg dose to -21.8% for the 2.5 mg dose after 2 years). Total triglycerides and lipoprotein(a) levels were also reduced. The decrease in total cholesterol and VLDL-C levels was not dose-dependent. Levels of LDL-C were unchanged. The clinical implication of these findings is not yet known.

Oestrogens may cause fluid retention, and therefore patients with cardiac or renal dysfunction should be carefully observed.

Women with pre-existing hypertriglyceridaemia should be monitored closely during oestrogen replacement or Hormone replacement therapy, since rare cases of large increases of plasma triglycerides leading to pancreatitis have been reported with oestrogen therapy in this condition.

Treatment with Tibolone Tablets results in a very minor decrease of thyroid binding globulin (TBG) and total T4. Levels of total T3 are unaltered. Tibolone Tablets decreases the level of sex-hormonebinding globulin (SHBG), whereas the levels of corticoid binding globulin (CBG) and circulating cortisol are unaffected.

Other medicines and Tibolone Tablets

Some medicines may interfere with the effect of Tibolone Tablets. This may lead to irregular bleeding. This undesirable effect will occur by using the following medicines:

•    Medicines against blood clotting (such as warfarin)

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

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

•    Medicines for tuberculosis (such as rifampicin)

•    Herbal remedies containing St John’s Wort used for depression (Hypericum perforatum).

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those 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 Tibolone Tablets, because this medicine can affect the results of some tests.

If you need to have surgery

If you are going to have surgery, make sure your doctor knows about it and also tell the surgeon that you are taking Tibolone Tablets. You may need to stop taking Tibolone Tablets about 4 to 6 weeks before the operation to reduce the risk of a blood clot (see section 2, ‘Blood clots in a vein’). Your doctor will inform you when you can start taking Tibolone Tablets again.

If you think that the impact of using Tibolone Tablets is too strong or too weak, please talk to your doctor or pharmacist.

Tibolone Tablets with Food and Drink

You can eat or drink normally while you are taking Tibolone Tablets.

Pregnancy, breast-feeding and fertility

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

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and Using Machines

Tibolone Tablets have no known effect on the ability to drive or use machines.

Tibolone Tablets contain Lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before you start using this medicine.

If you are worried about anything in this section, talk to your doctor about the risks and benefits of using HRT.

Do not take a progestogen preparation in addition to Tibolone Tablets.

How to take Tibolone Tablets

Swallow the tablet with a little water or other beverage.

If you take more Tibolone Tablets than you should

Severe symptoms are unlikely even if you take more than one tablet at the same time. In case of acute overdose, you may feel sick (nausea), or the state of being sick (vomiting) and some vaginal bleeding may occur. If necessary, please contact your doctor so that these symptoms can be treated.

If you forget to take Tibolone Tablets

If you forget to take a tablet at the usual time, you should take it as soon as possible unless more than 12 hours have passed since the time at which it was due. In this case, skip the missed tablet and take the next tablet at the usual time. Do not take a double dose to make up for the missed dose.

If you have any further questions on the use of Tibolone Tablets, please ask your doctor or pharmacist.

4. Possible side effects

3. How to take Tibolone Tablets

Always use Tibolone Tablets exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

When can you start taking Tibolone Tablets

If you are changing over from another type of HRT

There are several different types of HRT, such as in the tablet, patches and gel formulations. Most of these contain oestrogen or the combined oestrogen and progesterone. It is common with some kinds of HRT you will still have your periods, and some you don’t and these are referred to as “period-free HRT”.)

What to take into account when you start treatment with Tibolone Tablets.

If the menopause occurred naturally in your case, you should start taking Tibolone Tablets at the earliest 1 year after your last natural monthly bleeding. If your ovaries have been removed by surgery, you can start taking Tibolone Tablets immediately.

If you wish to start taking Tibolone Tablets and have had irregular or unexpected vaginal bleeding, please ensure that you contact the doctor who is treating you before starting Tibolone Tablets treatment, so that any malignant disease can be excluded.

If you wish to switch over to Tibolone Tablets from a medicinal product that contains an oestrogen and a progestogen, please ask your doctor what you should take into account.

How much Tibolone Tablets should you take and how often Unless otherwise prescribed by the doctor, the recommended dose is: One tablet daily after a meal, at the same time each day.

Your doctor will aim to prescribe the lowest dose to treat your symptoms for as short as necessary. Speak to your doctor if you think this dose is too strong or not strong enough.

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

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.

Tell your doctor or pharmacist if you are worried about any side effects which you think may be as a result of taking Tibolone Tablets. See also section 2 ‘Stop taking Tibolone Tablets and see your doctor immediately’

Serious side effects - see your doctor straight away

If you think you may have signs of a serious side effect, see a doctor straight away.

You may need to stop taking Tibolone Tablets if:

•    your blood pressure rises

•    your skin or the whites of your eyes go yellow (jaundice)

•    you suddenly have migraine-type headaches (see section 2 above)

•    you have signs of a blood clot (see section 2 above)

•    you get any of the problems listed in section 2 (Do not take Tibolone Tablets )

Other side effects

Common (affect up to 1 in 10 women):

•    breast pain

•    stomach or pelvic pain

•    unusual hair growth

•    vaginal bleeding or spotting.

This is usually nothing to worry about in the first few months of taking HRT. If bleeding continues, or starts after you have been on HRT for a while (also see Section 2).

•    vaginal problems such as more secretions, itching, irritation and thrush

•    thickening of the lining of the womb or the lining of the cervix

•    weight gain.

Uncommon (affects up to 1 in 100 women):

•    swollen hands, ankles or feet which is a sign of fluid retention

•    stomach upset

•    acne

•    painful nipples or breasts feeling uncomfortable

•    vaginal infections

Rare (affects up to 1 in 1,000 women):

•    itchy skin

Some women taking Tibolone Tablets have also reported:

•    depression, dizziness, headache

•    joint pain or muscle pain

•    skin problems such as rash or itching

•    loss of vision or blurred vision

•    changes in liver tests

There have been reports of breast cancer and of an increased cell growth or cancer of the lining of the womb in women using Tibolone Tablets.

Tell your doctor if any of the above mentioned side effects continues or becomes troublesome.

The following side effects have been reported as with other types of HRTs:

•    gall bladder disease

•    various skin disorders:

-    discolouration 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) Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme (Website: www.mhra.gov.uk/yellowcard). By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Tibolone Tablets

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

Do not use Tibolone Tablets after the expiry date which is stated on the carton/blister pack after EXP: The expiry date refers to the last day of that month.

Do not use this medicine if you notice the blister pack is damaged or even missing, despite the package being intact.

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 protect the environment.

This medicinal product does not require any special storage conditions.

6. Contents of the pack and other information

What Tibolone Tablets contains

The active substance is Tibolone.

One tablet contains 2.5 mg Tibolone.

The other ingredients are:

Potato starch, lactose monohydrate, magnesium stearate (Ph.Eur.) [vegetable origin], palmitoyl ascorbic acid (Ph.Eur.)

What Tibolone Tablets look like and contents of the pack

Tibolone Tablets are white to whitish, round tablets of approximately 6 mm diameter.

Tibolone Tablets are available in packs of 1 x 28 tablets and 3 x 28 tablets.

Marketing Authorisation Holder

Glenmark Pharmaceuticals Europe Limited Laxmi House, 2B Draycott Avenue,

Kenton, Middlesex, HA3 0BU.

United Kingdom

Manufacturer

Aristo Pharma GmbH Wallenroder Str. 8-10 D-13435 Berlin Germany or

Glenmark Pharmaceuticals Europe Limited Building 2, Croxley Green Business Park,

Croxley Green, Hertfordshire, WD18 8yA,    1

United Kingdom

This Package Leaflet was last revised in June 2016.

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