Livial

Package leaflet: Information for the user

Livial
2.5 mg, tablets
Tibolonum
Please read all of this leaflet carefully before 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 a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents:

1. What Livial is and what it is used for
2. What you need to know before taking Livial
3. How to take Livial
4. Possible side effects
5. How to store Livial
6. Contents of the pack and other information

1. What Livial is and what it is used for

Livial is a medicine used in Hormone Replacement Therapy (HRT). Livial contains tibolone –
a substance that has beneficial effects on various tissues and organs in the body, including bones. Livial
is used in postmenopausal women whose last natural menstrual period occurred at least 12 months
earlier.
Livial is used in the following cases:

Relief of postmenopausal symptoms
Around the time of menopause, the amount of oestrogens produced by a woman's body decreases.
This may cause symptoms such as hot flushes affecting the face, neck and chest. Livial relieves
postmenopausal symptoms in women. It is prescribed only when these symptoms seriously affect
daily life.

Prevention of osteoporosis
After menopause, some women may develop osteoporosis (thinning of the bones). Discuss all
available options with your doctor. Livial may be used to prevent postmenopausal osteoporosis in
women at increased risk of fractures due to osteoporosis, when other treatments are not suitable.

For more information on how Livial works – see section 6 "Other information".

2. Important information before using Livial

When not to use Livial:

• if any of the following conditions apply. If in doubt about any of the points listed below, consult your doctor before starting to take Livial.

When not to use Livial:

• If you are allergic to tibolone or any of the other ingredients of this medicine (listed in section 6).
• If you currently have, are suspected of having, or have previously had breast cancer.
• If you currently have estrogen-dependent malignant tumours or their presence is suspected (e.g. cancer of the endometrium - endometrial cancer).
• If you have unexplained vaginal bleeding.
• If you have atypical endometrial hyperplasia that is untreated.
• If you currently have or have previously had venous thrombosis, e.g. in the legs (deep vein thrombosis) or lungs (pulmonary embolism).
• If you have blood clotting disorders (e.g. protein C deficiency, protein S deficiency or antithrombin deficiency).
• If you currently have or have recently had arterial thrombosis (e.g. myocardial infarction, stroke or angina pectoris).
• If you currently have or have previously had liver disease and liver function has not returned to normal.
• If you have the rare inherited blood disorder called "porphyria".
• If you are pregnant or suspect you may be pregnant.
• If you are breastfeeding.

If any of the above conditions develops for the first time while taking Livial, you must stop taking the medicine immediately and contact your doctor without delay.

Medical history and regular check-ups

In addition to its benefits, hormone replacement therapy (HRT) and Livial carry certain risks that should be considered when deciding whether to start or continue treatment.

Experience with treating women who have experienced premature menopause (e.g. due to ovarian failure or surgical intervention) is limited. In cases of premature menopause, the risks associated with HRT or Livial may differ. Discuss this with your doctor.

Before starting HRT or Livial, your doctor should take a full medical history, including any family history of disease. Your doctor may decide to perform a physical examination, including breast and (or) gynecological examination (if necessary).

After starting Livial, regular check-ups are necessary (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing Livial.

You should attend regular breast examinations as recommended by your doctor.

Warnings and precautions

Inform your doctor if you have previously had any of the following conditions, as they may recur or worsen during treatment with Livial. In such cases, more frequent check-ups may be required:

• Uterine fibroids (leiomyomas)
• Endometriosis or previous excessive endometrial hyperplasia
• Increased risk of venous thrombosis (see "Venous thromboembolism")
• Increased risk of estrogen-dependent tumours (e.g. history of breast cancer in mother, sister or grandmother)
• Hypertension
• Liver disease, e.g. benign liver tumour
• Diabetes
• Gallstones
• Migraine or severe headaches
• Systemic autoimmune disorders (e.g. systemic lupus erythematosus)
• Epilepsy
• Asthma
• Otosclerosis (ear drum disorder leading to hearing loss)
• Very high blood fat levels (triglycerides)
• Fluid retention due to heart or kidney disease

Inform your doctor immediately if you experience any changes in your health while taking Livial.

HRT may occasionally cause fluid retention (oedema).

When to stop taking Livial and contact your doctor immediately

If any of the following conditions occur while taking HRT or Livial:

• Any of the conditions listed under "When not to use Livial"
• Yellowing of the skin or whites of the eyes (jaundice), which may indicate liver disease
• Increased blood pressure (which may cause headache, fatigue, dizziness)
• First occurrence of migraine-type headaches
• Pregnancy
• Suspected signs of blood clots such as:
  • Painful swelling and redness of the skin in the legs
  • Sudden chest pain
  • Difficulty breathing
    For more information – see section "Venous thromboembolism".

Note: Livial is not a contraceptive. Women under 50 years of age, or women who have had their last menstrual period less than 12 months ago, may need to use additional methods of contraception. Consult your doctor for advice.

HRT and malignant tumours

Endometrial hyperplasia and endometrial cancer

There are reports and studies on endometrial hyperplasia or endometrial cancer in women taking Livial. The risk of developing endometrial cancer increases with the duration of Livial therapy.

Irregular bleeding

Irregular bleeding or spotting may occur during the first 3–6 months of taking Livial.

However, if bleeding:

• Continues beyond the first 6 months,
• Occurs after 6 months of starting Livial,
• Persists after stopping Livial,
  you should contact your doctor as soon as possible.

Breast cancer

Data confirm that taking tibolone increases the risk of breast cancer. The additional risk depends on how long you take tibolone. Studies on HRT have shown that after stopping HRT, the additional risk decreases over time, but the risk may persist for 10 years or longer if HRT was taken for more than 5 years. There are no data on whether the risk persists after stopping tibolone, but a similar effect cannot be ruled out.

Comparison

Women taking Livial have a lower risk of breast cancer than women taking combined HRT, and a similar risk to women taking oestrogen-only HRT.

• You should regularly examine your breasts and contact your doctor if you notice any changes such as:
  • Dimpling of the skin
  • Changes in the nipples
  • Any visible or palpable lumps.

Ovarian cancer

Ovarian cancer is rare – much rarer than breast cancer. Taking oestrogen-only HRT or combined oestrogen-progestogen HRT is associated with a slightly increased risk of ovarian cancer.

The risk of ovarian cancer depends on age. For example, in women aged 50–54 not taking HRT, ovarian cancer will be diagnosed in about 2 out of 2000 women over 5 years. In women who have taken HRT for 5 years, it will occur in about 3 out of 2000 women (i.e. about one additional case).

With Livial, the risk of ovarian cancer is similar to that with other types of HRT.

Effects on heart and circulation

Venous thromboembolism

The risk of venous thromboembolism in women taking HRT is about 1.3–3 times higher than in women not taking such therapy, especially during the first year of treatment.

Blood clots can be dangerous. If a clot travels to the lungs, it may cause chest pain, breathlessness, fainting, or even death.

The likelihood of venous clots increases with age and with the following factors, which you should inform your doctor about (if applicable):

• Pregnancy or recent childbirth
• Use of oestrogens
• Inability to move (walk) for prolonged periods due to major surgery, injury or illness (in case of planned surgery, see also section 3)
• Significant overweight (body mass index BMI above 30 kg/m²)
• Any blood clotting disorders requiring long-term anticoagulant treatment
• Family history of blood clots in legs, lungs or other organs
• Systemic lupus erythematosus
• Malignant tumour.

Symptoms of thrombosis – see section "When to stop taking Livial and contact your doctor immediately".

Comparison

It is estimated that among women aged 50–59 not taking HRT, on average 4–7 out of 1000 will develop venous thrombosis over 5 years.

Among women of the same age taking oestrogen-progestogen HRT for 5 years, this number will be 9–12 per 1000 women (i.e. 5 additional cases).

When taking Livial, the increased risk of venous thromboembolism is lower than with other types of HRT.

Heart disease (myocardial infarction)

There is no evidence that Livial or HRT prevents heart attacks.

In women over 60 years of age taking oestrogen-progestogen HRT, there is a slightly higher likelihood of developing heart disease than in women not taking HRT. Since the risk of heart disease is closely age-related, the number of additional heart disease cases due to oestrogen-progestogen HRT is very small among healthy women approaching menopause, but increases with age.

There is no evidence that the risk of myocardial infarction with Livial differs from that with other types of HRT.

Stroke

Recent studies have shown that HRT and Livial increase the risk of stroke.

This increased risk has been observed mainly in postmenopausal women over 60 years of age.

Comparison

It is estimated that among women not taking Livial, the average number of strokes occurring over 5 years is 3 per 1000 women aged 50–59, while among women in this age group taking Livial, the number is 7 per 1000 (i.e. 4 additional cases).

Among women aged 60–69 not taking Livial, the average number of strokes occurring over 5 years is 11 per 1000, while among women in this age group taking Livial, the number is 24 per 1000 (i.e. 13 additional cases).

Other conditions

HRT does not prevent memory loss. Some data suggest a higher risk of memory loss in women starting HRT after age 65. Consult your doctor for advice.

Livial and other medicines

Some medicines may affect the action of Livial, leading to irregular bleeding. These include:

• Anticoagulant medicines (e.g. warfarin)
• Antiepileptic medicines (e.g. phenobarbital, phenytoin and carbamazepine)
• Antituberculosis medicines (e.g. rifampicin)
• Herbal preparations containing St John's wort (Hypericum perforatum).

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those obtained without a prescription, herbal supplements and other natural products.

Livial with food and drink

Food and drink do not affect the administration of Livial.

Pregnancy and breastfeeding

Livial is intended for use only in postmenopausal women. If you become pregnant, stop taking Livial and consult your doctor.

Driving and operating machinery

According to current data, Livial has no effect on alertness or concentration.

Livial contains lactose.

If you have been diagnosed with an intolerance to certain sugars, consult your doctor before taking Livial.

3. How to take Livial

Livial is intended for oral use. One tablet should be taken daily.
Swallow the tablet with a small amount of water or another liquid. The medicine should be taken
every day at approximately the same time.
The Livial tablet blisters are marked with days of the week. Treatment should be started by taking the tablet marked with the correct day. For example, if the first tablet is taken on Monday, take the tablet marked in the top row of the pack as Monday, and continue taking the tablets daily in the order of the week until the pack is empty.
The first tablet from the next pack should be taken the following day, without any break.

In the case of natural menopause, Livial should not be used until twelve months have passed since the last menstrual bleeding. If Livial is started earlier, the risk of irregular vaginal bleeding may increase.

For symptom relief, your doctor will prescribe the lowest effective dose to be used for the shortest possible duration. If you feel that the effect of Livial is too strong or too weak, consult your doctor.

Overdose of Livial
If you take more Livial than recommended, contact your doctor or pharmacist immediately.
If several tablets are taken at the same time, there is generally no cause for concern, but you should inform your doctor immediately. Symptoms of overdose may include nausea, vomiting, or vaginal bleeding.

Missed dose of Livial
Take the missed tablet as soon as possible, unless more than 12 hours have passed since the previous tablet was taken. In that case, skip the missed tablet and take the next dose at the usual time.
Do not take a double dose to make up for a missed dose.

Surgery
Before any planned surgery, inform your doctor that you are taking Livial. To reduce the risk of venous thrombosis, it may be necessary to stop taking Livial 4 to 6 weeks before the operation (see section 2 "Venous thrombosis"). Your doctor will decide when you can restart taking Livial.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although they do not occur in everyone.
Compared to women not using HRT, women using such therapy have been observed to more frequently develop the following diseases:

• breast cancer
• abnormal growth or cancer of the uterine lining (endometrial hyperplasia or endometrial cancer)
• ovarian cancer
• venous thrombosis in the lower limbs and lungs (venous thromboembolic disease)
• heart diseases
• stroke
• possible memory loss (dementia) when HRT is initiated after the age of 65.

For further information on the above adverse effects – see section 2.
Common adverse effects observed in clinical trials (occurring in at least 1 in 100 to 1 in 10 women using Livial) are:

• lower abdominal pain,
• atypical excessive hair growth,
• hot flushes,
• thickening of the endometrial layers (uterine mucosa),
• bleeding after menopause,
• breast tenderness,
• genital itching,
• vaginal candidiasis,
• vaginal bleeding,
• pelvic pain,
• cervical dysplasia,
• genital discharge,
• vulvovaginal inflammation,
• weight gain,
• abnormal cervical smear.

Less frequently occurring adverse effects (occurring in at least 1 in 1000 to 1 in 00 women using Livial) include:

• acne,
• breast discomfort,
• fungal infections,
• vaginal mycosis,
• nipple pain.

Other adverse effects observed after Livial was introduced to the market include:

• dizziness,
• rash, itching, seborrheic dermatitis,
• headache, migraine,
• visual disturbances (including blurred vision),
• gastrointestinal disorders,
• depression,
• fluid retention, oedema,
• joint and muscle pain,
• liver function abnormalities.

Most of these adverse effects are mild in nature.
Cases of breast cancer, endometrial hyperplasia, and endometrial cancer have been reported in women taking Livial.
If vaginal bleeding or spotting occurs, or if any of the above symptoms worsen or do not resolve, you should inform your doctor.
When other types of HRT are used, the following adverse effects have been reported:

• gallbladder diseases
• skin changes, such as:
• skin pigmentation (particularly on the face and neck), known as melasma;
• painful red nodules on the skin (erythema nodosum);
• rash with localized redness, swelling or ulceration (erythema multiforme and vasculitis).

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department for Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl.
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Livial

Keep the medicine out of the sight and reach of children.
Store between 2°C and 25°C. Protect from light and moisture.
Check whether the packaging contains information regarding special storage conditions.
Do not use this medicine after the expiry date stated on the carton and blister pack after "EXP".
The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the pack and other information

The most important natural sex hormones in women are estrogens and progesterone.
They are essential for normal sexual development and functioning in women, and also play
an important role in regulating the menstrual cycle. Estrogens also play a key role in bone formation.
Bone is built up during adolescence, and peak bone mass is achieved between the ages of 20–30 years.
After this, bone mass gradually decreases, initially slowly, but over time bone loss accelerates, especially after menopause.
The perimenopausal period usually occurs in women around the age of 50, when the ovaries gradually stop producing estrogens.
If the ovaries are surgically removed before menopause, the decline in hormone production occurs abruptly.
The cessation of estrogen production leads to the appearance of well-known symptoms such as hot flushes and night sweats.
Additionally, a deficiency of sex hormones may cause vaginal dryness and thinning of the vaginal mucosa.
As a result, sexual intercourse may become painful, and vaginal infections may occur more frequently.
Physical problems may coexist in some women with mood changes, nervousness, depression, irritability, and loss of libido.
A frequently overlooked problem is the accelerated loss of bone density during the perimenopausal period and after menopause.
Bones gradually become fragile and are prone to fractures (osteoporosis), particularly in the spine, hip joints, and wrists.
Osteoporosis may also contribute to back pain, changes in spinal shape (kyphosis), and reduced height.
The medicine Livial contains tibolone, a substance that exerts beneficial effects on various tissues and organs in the body, reducing menopausal symptoms such as hot flushes and night sweats. Tibolone has a positive effect on the vaginal lining, mood, and sexual desire. Livial may also inhibit the decline in bone density occurring after menopause in the bones of the spine, hip joints, and wrists. Unlike other forms of hormone replacement therapy, Livial does not stimulate the endometrium; therefore, treatment with Livial does not result in monthly bleeding.
What Livial contains

• The active substance is 2.5 mg tibolone.
• The other ingredients are: potato starch, magnesium stearate, ascorbyl palmitate, lactose.

What Livial looks like and contents of the pack
Livial 2.5 mg tablets are white in colour, marked with "MK2" on one side and "Organon" on the other.
28 tablets in a PVC/Al blister pack, in a cardboard carton.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Organon Polska Sp. z o.o.
ul. Marszałkowska 126/134
00-008 Warszawa
Tel.: + 48 22 306 57 64
[email protected]
Manufacturer
N.V. Organon, Kloosterstraat 6, 5349 AB Oss, The Netherlands