Ladybon

Patient Information Leaflet

Warning! Please keep this leaflet. The packaging information is in a foreign language.
Ladybon (Tibolona Zentiva)
2.5 mg, tablets
Tibolonum
Ladybon and Tibolona Zentiva are different brand names for the same medicine.
Please read this leaflet carefully before taking the medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of Contents

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

1. What Ladybon is and what it is used for

Ladybon is a medicine used in Hormone Replacement Therapy (HRT). It contains tibolone,
an active substance that has beneficial effects on various tissues and organs in the body, such as the brain, vagina, and
bones. Ladybon is used in postmenopausal women, in whom at least 12 months (1 year) have passed since the last natural menstrual period.
Ladybon is used for:
Relief of postmenopausal symptoms
During menopause (natural or following surgical removal of the ovaries), the amount of estrogen produced by a woman's body decreases. This may cause symptoms such as sudden feelings of heat in the face, neck, and chest (hot flushes). Ladybon reduces these postmenopausal symptoms. Ladybon is prescribed only when these symptoms significantly impair daily life.
Prevention of osteoporosis
After menopause, some women may develop weakened bones (osteoporosis). Please discuss all available treatment options with your doctor.
If there is an increased risk of fractures due to osteoporosis and other medicines cannot be used, Ladybon may be prescribed to prevent postmenopausal osteoporosis.
Further information about Ladybon and its uses can be found in section 6.

2. Important information before using the medicine Ladybon

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Medical history and regular check-ups
HRT is associated with risks that should be considered when deciding whether to start or continue treatment.
Experience in treating women with premature menopause (due to ovarian failure or surgical intervention) is limited. If a patient has experienced premature menopause, the risks associated with using HRT or tibolone may differ. This should be discussed with a doctor.
Before starting (or restarting) HRT, the doctor will take a medical history regarding the patient's health status and any family history of disease. The doctor may decide to perform a physical examination, which may include a breast examination and/or a gynaecological examination, if necessary.
After starting treatment with Ladybon, the patient should attend regular check-ups (at least once a year). During these visits, the patient should discuss with the doctor the benefits and risks of continuing treatment with Ladybon.
The patient must be certain that:

• She regularly undergoes breast screening and cervical smear tests as recommended by her doctor.
• She regularly examines her breasts for any changes, such as skin dimpling, changes in the nipple, or any lumps that she can see or feel.

When not to use Ladybon
If any of the following situations apply to the patient or if the patient has any doubts, she should consult a doctor before starting treatment with Ladybon.

• If the patient is allergic to tibolone or any of the other ingredients of this medicine (listed in section 6).
• If the patient is pregnant or suspects she may be pregnant.
• If the patient is breastfeeding.
• If the patient has or has had breast cancer, or if there is suspicion of breast cancer.
• If the patient has a hormone-dependent cancer, such as cancer of the lining of the womb (endometrium), or if there is suspicion of such a cancer.
• If the patient has unexplained vaginal bleeding.
• If the patient has excessive growth of the lining of the womb (endometrial hyperplasia) that is untreated.
• If the patient has or has had blood clots in the veins (thrombosis), e.g., in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism).
• If the patient has or has had blood clotting disorders (e.g., protein C deficiency, protein S deficiency, or antithrombin deficiency).
• If the patient has or has had arterial diseases caused by blood clots, such as heart attack, stroke or angina pectoris.
• If the patient has or has had liver disease, and liver function test results have not returned to normal.
• If the patient has a rare inherited blood disorder called "porphyria".

If any of the above conditions occurs for the first time during treatment with Ladybon, the patient should stop taking the medicine immediately and consult a doctor without delay.
If the patient has entered menopause, she should not take Ladybon earlier than 12 months after her last natural menstrual period. If the medicine is taken earlier, irregular bleeding may occur.
Warnings and precautions
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The patient should inform her doctor about any of the following conditions experienced in the past, as they may recur or worsen during treatment with Ladybon. If any of the following conditions occur, the patient should see a doctor regardless of her scheduled check-up:

• Uterine fibroids.
• Presence of endometrial tissue outside the uterus (endometriosis) or history of endometrial hyperplasia.
• Increased risk of blood clots (see "Blood clots in the veins (thrombosis)").
• Increased risk of oestrogen-sensitive cancers (such as history of breast cancer in mother, sister or grandmother).
• High blood pressure.
• Liver disease, such as benign liver tumour.
• Diabetes.
• Gallstones.
• Migraine or severe headaches.
• Autoimmune disease affecting multiple organs (systemic lupus erythematosus - SLE).
• Epilepsy.
• Bronchial asthma.
• Disease affecting the eardrum and hearing (otosclerosis).
• Very high levels of blood lipids (triglycerides).
• Fluid retention due to heart or kidney disease.

The patient should stop taking Ladybon and contact her doctor immediately if any of the following conditions occur during treatment with HRT or tibolone:

• Any of the conditions listed under "When not to use Ladybon".
• Yellowing of the skin or whites of the eyes (jaundice). These may be symptoms of liver disease.
• Significant increase in blood pressure (symptoms may include headache, fatigue, dizziness).
• First occurrence of migraine-type headache.
• If pregnancy occurs.
• If symptoms of blood clots occur, such as:
  • Painful swelling and redness in the legs,
  • Sudden chest pain,
  • Difficulty breathing.

More information in "Blood clots in the veins (thrombosis)".
Note: Ladybon is not a contraceptive. If less than 12 months have passed since the last menstrual bleeding or if the patient is under 50 years of age, additional contraception may still be necessary to prevent pregnancy. The patient should consult her 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)
Cases of excessive endometrial cell growth or cancer of the endometrium have been reported in women using tibolone (the active substance in Ladybon). The longer the medicine is used, the greater the risk of developing endometrial cancer.
Irregular bleeding
Irregular bleeding or spotting may occur during the first 3–6 months of treatment with Ladybon.
However, if irregular bleeding:

• Continues beyond the first 6 months of treatment,
• Begins after more than 6 months of treatment with Ladybon,
• Persists even after stopping Ladybon,

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the patient should consult a doctor as soon as possible.
Breast cancer
Data confirm that taking tibolone increases the risk of developing breast cancer. The additional risk depends on how long the patient takes tibolone. In studies on HRT, it was found that after stopping HRT, the additional risk decreases over time, but the risk may persist for 10 years or longer if a woman has used HRT for more than 5 years.
There are no data on the persistence of risk after stopping tibolone treatment, but a similar effect cannot be ruled out.
Comparison
Women taking Ladybon have a lower risk of developing breast cancer than women taking combined HRT and a comparable risk to women taking oestrogen-only HRT.

• The patient should regularly examine her breasts and consult a doctor if she notices any of the following changes:
  • Skin dimpling.
  • Changes in the nipples.
  • Any visible or palpable lumps.

Ovarian cancer
Ovarian cancer is rare – significantly less common than breast cancer. Using oestrogen-only or combined oestrogen-progestogen HRT is associated with a slightly increased risk of ovarian cancer.
The risk of developing ovarian cancer changes with age. For example, among women aged 50 to 54 who do not use HRT, ovarian cancer will be diagnosed in about 2 out of 2000 over a 5-year period. Among women who have used HRT for 5 years, there will be approximately 3 cases per 2000 (i.e., about 1 additional case).
The increase in risk of ovarian cancer during treatment with Ladybon is similar to that with other types of HRT.
Effects of HRT on the heart and circulatory system
Blood clots in the veins (thrombosis)
The risk of developing blood clots in the veins is about 1.3 to 3 times higher in women using HRT than in women not using it, especially during the first year of use.
Blood clots can be dangerous, and if a clot travels to the lungs, it may cause chest pain, shortness of breath, fainting, or even death.
The likelihood of blood clots increases with age and if any of the following conditions apply. The patient should inform her doctor if any of the following apply:

• If the patient is pregnant or has recently given birth.
• If the patient is taking oestrogens.
• If she is unable to walk for a prolonged period due to major surgery, injury, or illness (see also section 3 "If surgery is required").
• If the patient has significant obesity (BMI >30 kg/m²).
• If she has any condition causing increased blood clotting requiring long-term anticoagulant treatment.
• If any close relative has ever had a blood clot in the leg, lungs, or another organ.
• If the patient has systemic lupus erythematosus.
• If the patient has cancer.

Symptoms of blood clots are listed under "The patient should stop taking Ladybon and contact her doctor immediately".
Comparison
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Among women aged 50 to 59 who do not use HRT, approximately 4 to 7 out of 1000 can be expected to develop venous thrombosis over a 5-year observation period.
Among women aged 50 to 59 who use oestrogen-progestogen HRT for more than 5 years, venous thrombosis can be expected in 9 to 12 out of 1000 women (i.e., 5 additional cases).
During treatment with Ladybon, the increase in risk of venous thrombosis is lower than with other types of HRT.
Heart disease (heart attack)
There is no evidence that HRT prevents heart attacks.
In women over 60 years of age who use oestrogen-progestogen HRT, there is a slightly increased risk of heart disease compared to women not using HRT. Since the risk of heart disease depends greatly on age, the number of additional cases of heart disease caused by oestrogen-progestogen HRT is very low in healthy women approaching menopause, but increases with age.
Stroke
Recent studies indicate that hormone replacement therapy and tibolone increase the risk of stroke. This increased risk has been observed mainly in women over 60 years of age.
Other factors that may increase the risk of stroke include:

• Ageing
• High blood pressure
• Smoking
• Excessive alcohol consumption
• Irregular heartbeat

Comparison
Considering women aged 50–59 who do not use tibolone, an average of 3 strokes per 1000 women can be expected over 5 years. Among women aged 50–59 using tibolone, this number would be 7 per 1000 (i.e., 4 additional cases).
Considering women aged 60–69 who do not use tibolone, an average of 11 strokes per 1000 women can be expected over 5 years. Among women aged 60–69 using tibolone, this number would be 24 per 1000 (i.e., 13 additional cases).
Other conditions

• HRT does not prevent memory loss. There is some evidence of an increased risk of memory loss in women who start HRT after age 65. The patient should consult her doctor.

Ladybon and other medicines
The patient should inform her doctor or pharmacist about all medicines she is currently taking, has recently taken, or plans to take.
Some medicines may affect the action of Ladybon. This may lead to irregular bleeding. These include:

• Anticoagulant medicines (such as warfarin).
• Medicines used to treat epilepsy (such as phenobarbital, phenytoin and carbamazepine).
• Medicines used to treat tuberculosis (such as rifampicin).
• Herbal preparations containing St John's wort ( Hypericum perforatum ).

Ladybon with food and drink
The patient may eat and drink normally while taking Ladybon.
Pregnancy and breastfeeding
Ladybon is intended only for postmenopausal women. If the patient becomes pregnant, she should stop taking Ladybon and contact her doctor.
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Ladybon should not be used during pregnancy or breastfeeding, or if pregnancy is suspected.
Driving and operating machinery
According to available data, Ladybon does not affect the ability to drive or operate machinery.
Ladybon contains monohydrate lactose
If the patient has previously been diagnosed with intolerance to certain sugars, she should consult her doctor before taking this medicine.

3. How to use Ladybon

This medicine should always be used as directed by a doctor or pharmacist. If in doubt,
consult your doctor or pharmacist.
Ladybon is intended for oral use. Take one tablet once daily. Swallow the tablet with a small amount of water or another liquid, preferably at the same time each day.
Do not start taking Ladybon until 12 months after your last natural menstrual period. Starting Ladybon earlier may increase the risk of irregular vaginal bleeding.
For symptom treatment, your doctor will prescribe the lowest possible dose for the shortest possible duration. If you feel the dose is too high or too low, consult your doctor.
If surgery is required
If surgery is required, inform the surgeon that you are taking Ladybon. It may be necessary to stop taking Ladybon approximately 4 to 6 weeks before the scheduled operation to reduce the risk of blood clots (see section 2, "Blood clots (thrombosis)"). Consult your doctor to determine when it is safe to restart Ladybon.
Taking more Ladybon than recommended
If you take more tablets than recommended, contact your doctor or pharmacist immediately.
Although there is no immediate cause for concern if you take too many tablets, you should still contact your doctor without delay. Symptoms of overdose may include nausea, vomiting, or vaginal bleeding.
Missed dose of Ladybon
If you miss a dose, take it as soon as possible, unless more than 12 hours have passed since the missed dose. If more than 12 hours have passed, simply skip the missed dose.
Do not take a double dose to make up for a missed dose.
Stopping Ladybon
Do not stop taking Ladybon before the recommended treatment period is complete, unless advised by your doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although they do not occur in everyone.
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Most symptoms are mild in severity.
The following conditions have been observed more frequently in women using HRT compared to women not using HRT:

• Breast cancer.
• Abnormal growth or cancer of the uterine lining (endometrial hyperplasia or cancer).
• Ovarian cancer.
• Venous thrombosis in the lower limbs or lungs (venous thromboembolic disease).
• Heart disease.
• Stroke.
• Probable memory loss if HRT is initiated after the age of 65. More information on the above adverse reactions is provided in section 2.

Other adverse reactions
The following adverse reactions have been reported in clinical trials in women taking tibolone (the active substance in Ladybon):

Common (may occur in less than 1 in 10 people):

• Spotting or vaginal bleeding.
• Abdominal pain.
• Weight gain.
• Breast tenderness.
• Unnatural hair growth.
• Vaginal symptoms such as itching, discharge, or thrush.
• Thickening of the endometrium or cervical mucosa.

Uncommon (may occur in less than 1 in 100 people):

• Swelling of hands, ankles or feet – sign of fluid retention.
• Stomach upset.
• Acne.
• Painful nipples or discomfort in the breasts.
• Vaginal infections.

Rare (may occur in less than 1 in 1,000 people):

• Skin itching.

Other adverse reactions reported after tibolone has been marketed include:

• Dizziness, headache, migraine, depression.
• Rash.
• Visual disturbances, loss of vision or blurred vision.
• Joint or muscle pain.
• Liver function disorders.

Cases of breast cancer and excessive growth of cells or cancer of the endometrium have been reported in women taking tibolone.
You should inform your doctor if you experience vaginal bleeding or spotting, or if any of the symptoms listed above become troublesome or worsen.

The following adverse reactions have been observed with other types of HRT:

• Gallbladder diseases.
• Various skin disorders:
  • Skin pigmentation, especially on the face or neck, known as “pregnancy mask” (chloasma).
  • Painful red skin nodules (erythema nodosum).
  • Changes in ring-shaped lesions with erosions (erythema multiforme).

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

5. How to store Ladybon

Keep the medicine out of the sight and reach of children.
Do not use this medicine if you notice any visible signs of deterioration.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Store below 25ºC. Keep in the original packaging to protect from light and moisture.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the packaging and other information

What Ladybon contains
The active substance is tibolone. Each tablet contains 2.5 mg of tibolone. Other ingredients are: monohydrate lactose, potato starch, ascorbyl palmitate (E 304), magnesium stearate.

What Ladybon looks like and contents of the pack

White or almost white, flat, round tablets, with an embossed mark “ ” on one side.
Pack sizes: 1×28 or 3×28 tablets.
For more detailed information, please contact the marketing authorisation holder or the parallel importer.

Marketing authorisation holder in Portugal, country of export:
Zentiva Portugal, Lda, Miraflores Premium I, Alameda Fernão Lopes, 16 A - 8º piso A, 1495-190 Algés, Portugal

Manufacturer:
Zentiva k.s., U kabelovny 130, Dolní Měcholupy, Prague 10, 102 37, Czech Republic

Parallel importer:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź

Repackaged in:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź

Marketing authorisation number in Portugal, country of export: 5394531
Parallel import authorisation number: 155/23

More information about Ladybon
The most important natural sex hormones in women are estrogens and progesterone. They are necessary for normal sexual development and regulation of the menstrual cycle.

Estrogens are also important in bone formation. Bone mass builds up during youth, and peak bone mass is achieved between the ages of 20 and 30. After that, bone mass gradually decreases, initially slowly, but later more rapidly, especially after menopause. Menopause is the time (usually around age 50) when the ovaries gradually stop producing estrogens. If the ovaries are surgically removed before menopause, the drop in hormone levels occurs very rapidly.

Reduced hormone production often causes symptoms such as hot flushes and night sweats. A lack of sex hormones may also cause the vaginal mucosa to become thinner and drier. As a result, sexual intercourse may become painful and vaginal infections may occur more frequently. Some women may also experience mood changes, nervousness, depression, irritability, and loss of libido.

A frequently overlooked problem is the accelerated loss of bone mass during and after menopause. Bones gradually become fragile and prone to fractures (osteoporosis), particularly in the spine, hip, and wrist. Osteoporosis may also cause back pain, reduced height, and so-called "dowager's hump".

Ladybon contains tibolone, a substance that exerts beneficial effects on tissues in various parts of the body, such as the brain, vagina, and bones, thereby relieving symptoms such as hot flushes and night sweats, and improving the condition of the vaginal mucosa, mood, and libido. Ladybon may also inhibit the loss of bone mass occurring after menopause in the spine, hip, and wrists. Unlike some hormone replacement therapies, Ladybon does not affect the endometrium. Therefore, treatment with Ladybon does not cause monthly vaginal bleeding.

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