Ladybon

Package leaflet: Information for the user

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language.
Ladybon (Tibolona Zentiva 2.5 mg)
2.5 mg, tablets
Tibolonum
Ladybon and Tibolona Zentiva 2.5 mg are different brand names of the same medicine.
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult 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 adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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,
a substance that has beneficial effects on various tissues and organs of the body, such as the brain, vagina, and
bones. Ladybon is used in women who are postmenopausal, i.e. in whom at least 12 months (1 year) have passed since their 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
estrogens 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 helps reduce 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). You should discuss all available treatment options with your doctor.
If you have 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 Ladybon

Medical interview and regular check-ups
Hormone replacement therapy (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 and any family medical conditions. The doctor may decide to perform a physical examination, which may include a breast examination and/or a gynecological 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 ensure 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 must consult her 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 breast cancer is suspected.
• If the patient has an estrogen-dependent tumour, such as cancer of the lining of the womb (endometrium), or if such a tumour is suspected.
• 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 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 must stop taking the medicine immediately and consult her 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 used earlier, irregular bleeding may occur.

Warnings and precautions
The patient should inform her doctor if she has previously experienced any of the following conditions, as they may recur or worsen during treatment with Ladybon. If any of the following conditions occur, the patient should see her doctor immediately, 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 estrogen-sensitive cancer (e.g. 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 must 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.
• Marked 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.

See more information under "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 needed to prevent pregnancy. Please consult your doctor for advice.

HRT and tumours

Excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the lining of the womb (endometrial cancer)
Cases of excessive cell growth or cancer of the lining of the womb (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 cancer of the endometrium.

Irregular bleeding
During the first 3–6 months of treatment with Ladybon, irregular bleeding or spotting may occur.
However, if irregular bleeding:

• persists beyond the first 6 months of treatment,
• starts after more than 6 months of using Ladybon,
• continues even after stopping Ladybon,
  the patient should contact her 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 uses 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 the woman used HRT for more than 5 years.
There is no data on the persistence of risk after stopping tibolone treatment, but a similar effect cannot be ruled out.
Comparison
Women using Ladybon have a lower risk of developing breast cancer than women using combined HRT, and a comparable risk to women using oestrogen-only therapy.

• The patient should regularly examine her breasts and contact her 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 rarer than breast cancer. Using oestrogen-only or combined oestrogen-progestagen 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 increased risk of ovarian cancer during treatment with Ladybon is similar to that with other types of HRT.

Effects of HRT on the heart and circulation

Blood clots in the veins (thrombosis)
The risk of venous blood clots is about 1.3 to 3 times higher in women using HRT than in women not using it, especially during the first year of treatment.
Blood clots can be life-threatening; if a clot travels to the lungs, it may cause chest pain, shortness of breath, fainting, or even death.
The likelihood of developing 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 using 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 overweight (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 must stop taking Ladybon and contact her doctor immediately".

Comparison
Among women aged 50 to 59 who do not use HRT, an average of 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-progestagen 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 using oestrogen-progestagen HRT, there is a slightly increased risk of heart disease compared to women not using HRT. Since the risk of heart disease strongly depends on age, the number of additional cases caused by oestrogen-progestagen 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 is mainly observed 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
Among women aged 50–59 who do not use tibolone, an average of 3 stroke cases 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).
Among women aged 60–69 who do not use tibolone, an average of 11 stroke cases 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 the age of 65. Please consult your 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, which 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 products 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 must stop taking Ladybon and contact her doctor.
Ladybon must not be used during pregnancy or breastfeeding, or if pregnancy is suspected.

Driving and using machines
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 taken exactly as directed by your doctor or pharmacist. If you have any doubts,
please consult your doctor or pharmacist.
Ladybon is intended for oral administration. Take one tablet once daily. Tablets should be taken with a small amount of water or another liquid, preferably at the same time each day.
Do not start taking Ladybon until at least 12 months have passed since 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 of the medicine is too high or too low, please consult your doctor.

If surgery is required
If surgery is necessary, 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 in veins"). Please consult your doctor to determine when it will be safe to restart Ladybon.

Taking more Ladybon than recommended
If you take more tablets than recommended, contact your doctor or pharmacist immediately.
There is generally no cause for serious concern if you have taken too many tablets, but you should still contact your doctor immediately. Symptoms of overdose may include nausea, vomiting, or vaginal bleeding.

Missed dose of Ladybon
If you miss a tablet, 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 that 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 over, 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 effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Most symptoms are mild in severity.
The following diseases have been observed more frequently in women using HRT compared to women not using HRT:

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

Other adverse effects
The following adverse effects have been reported in clinical studies 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.
• Hirsutism (excessive hair growth).
• Vaginal symptoms such as itching, discharge or candidiasis.
• Thickening of the endometrium or cervical mucosa.

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

• Swelling of the hands, ankles or feet – a 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):

• Itching of the skin.

Other adverse effects reported after tibolone became available on the market 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 cell growth 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 effects have been observed with other types of HRT:

• Gallbladder disease.
• Various skin disorders:
• • Skin pigmentation, especially on the face or neck, known as “melasma” (chloasma).
• • painful red skin nodules (erythema nodosum).
• • changes in the shape of lesions with central necrosis (erythema multiforme).

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

5. How to store the medicine 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 25°C, 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 required. 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: 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 "e" 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:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw, Poland

Repackaged in:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw, Poland

Marketing authorisation number in Portugal, country of export: 5394531
Parallel import authorisation number: 393/22

More information about the medicinal product Ladybon
The most important natural sex hormones in women are estrogens and progesterone. These are necessary for normal sexual development and regulation of the menstrual cycle.
Estrogens are also important in the process of bone formation. Bone is built up during youth, and maximum 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 decrease in hormone production occurs very rapidly.

Reduced hormone production often causes symptoms such as hot flushes and night sweats. A deficiency of sex hormones may also cause the vaginal mucosa to become thinner and dry. As a result, sexual intercourse may be 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 lead to back pain, reduced height, and the 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 alleviating symptoms such as hot flushes and night sweats, and improving the condition of the vaginal mucosa, mood, and libido.
Ladybon may also inhibit the process of postmenopausal bone loss 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.