Ladibon

Leaflet attached to the packaging: patient information

LADYBON, 2.5 mg, tablets

Tibolone

Read the leaflet carefully before taking the medicine, as it contains

important information for the patient.

• The leaflet should be kept in case it needs to be read again.
• In case of any doubts, the doctor or pharmacist should be consulted.
• This medicine has been prescribed specifically for one person. It should not be given to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Ladybon and what is it used for
• 2. Important information before taking Ladybon
• 3. How to take Ladybon
• 4. Possible side effects
• 5. How to store Ladybon
• 6. Package contents and other information

1. What is Ladybon and what is it used for

Ladybon is a medicine used in Hormone Replacement Therapy (HRT). It contains tibolone, a substance that has a beneficial effect on various tissues and organs of the body, such as the brain, vagina, and bones. Ladybon is used in postmenopausal women, at least 12 months (1 year) after their last natural menstrual period.

Ladybon is used to:

Relieve symptoms that occur after menopause
During menopause (natural or after surgical removal of the ovaries), the amount of estrogen produced by the woman's body decreases. This can cause symptoms such as a feeling of heat on the face, neck, and chest ("hot flashes"). Ladybon reduces these symptoms after menopause. Ladybon is prescribed only if the above symptoms significantly interfere with daily life.
Prevent the occurrence of osteoporosis
After menopause, some women may experience bone weakness (osteoporosis). All available treatment options should be discussed with the doctor.
If there is an increased risk of fractures due to osteoporosis and other medicines cannot be used, Ladybon may be used to prevent osteoporosis after menopause.
More information about Ladybon and its use can be found in section 6.

2. Important information before taking Ladybon

Medical history and regular check-ups

The use of HRT is associated with risks that should be considered when deciding to start or continue treatment.
Experience in treating women with premature menopause (due to ovarian failure or surgery) is limited. If a patient has had premature menopause, the risks associated with HRT or tibolone may be different.
This should be discussed with the doctor.
Before starting treatment (or re-starting) HRT, the doctor will take a medical history and ask about the patient's health and any family illnesses. The doctor may decide to perform a physical examination, which may include a breast examination and/or gynecological examination if necessary.
After starting Ladybon, the patient should attend regular check-ups (at least once a year). During these visits, the patient should discuss the benefits and risks of continuing treatment with Ladybon with the doctor.
The patient must be sure to:

• Regularly undergo breast screening and cervical smear testsas recommended by the doctor.
• Regularly check their breastsfor any changes, such as skin depressions, changes in the nipple, or any lumps that can be seen or felt.

When not to take Ladybon

If any of the following situations apply to the patient or if the patient has any doubts, they should consult a doctorbefore taking Ladybon.

• If the patient is allergicto tibolone or any of the other ingredients of this medicine (listed in section 6).
• If the patient is pregnant or suspects pregnancy.
• If the patient is breastfeeding.
• If the patient has or has had breast cancer, or if there is a suspicion of breast cancer.
• If the patient has estrogen-dependent cancer, such as endometrial cancer (cancer of the lining of the uterus), or if there is a suspicion of this cancer.
• If the patient has unexplained vaginal bleeding.
• If the patient has untreated endometrial hyperplasia(thickening of the lining of the uterus).
• If the patient has or has had blood clots in the veins(thrombosis), e.g., in the legs (deep vein thrombosis) or lungs (pulmonary embolism).
• If the patient has blood clotting disorders(e.g., deficiency of protein C, protein S, or antithrombin).
• If the patient has or has had arterial diseasescaused by blood clots, such as heart attack, stroke, or angina.
• If the patient has or has had liver disease, and liver function tests have not returned to normal.
• If the patient has a rare blood disorder called porphyria, which is inherited.

If any of the above conditions occur for the first time while taking Ladybon, the patient should stop taking the medicine and consult a doctor immediately.
If the patient has started menopause, they should not take Ladybon until at least 12 months after their last natural menstrual period. If Ladybon is taken earlier, irregular bleeding may occur.

Warnings and precautions

The doctor should be informed about any of the following conditions before starting treatment, as they may recur or worsen while taking Ladybon. If any of the following conditions occur, the patient should consult a doctor, regardless of the scheduled check-up:

• Uterine fibroids.
• Endometriosis or a history of endometrial hyperplasia.
• Increased risk of blood clots (see "Blood clots in the veins (thrombosis)").
• Increased risk of estrogen-dependent cancer (e.g., a family history of breast cancer).
• High blood pressure.
• Liver disease, such as a benign liver tumor.
• Diabetes.
• Gallstones.
• Migraine or severe headaches.
• Systemic lupus erythematosus (SLE), a disease that affects many parts of the body.
• Epilepsy.
• Asthma.
• Otosclerosis, a disease that affects the eardrum and hearing.
• Very high levels of triglycerides in the blood.
• Fluid retention due to heart or kidney disease.

The patient should stop taking Ladybon and consult a doctor immediately

if any of the following conditions occur while taking HRT or tibolone:

• Any of the conditions listed in "When not to take Ladybon".
• Yellowing of the skin or whites of the eyes (jaundice), which may be a sign of liver disease.
• A significant increase in blood pressure (symptoms may include headache, fatigue, dizziness).
• A migraine headache that occurs for the first time.
• If the patient becomes pregnant.
• If the patient experiences symptoms of a blood clot, such as:
• Painful swelling and redness of the legs,
• Sudden chest pain,
• Difficulty breathing.

More information can be found in "Blood clots in the veins (thrombosis)".
Note: Ladybon is not a contraceptive. If it has been less than 12 months since the last menstrual period or the patient is under 50 years old, additional contraception may be needed to prevent pregnancy. The patient should consult a doctor for advice.
HRT and cancer
Endometrial hyperplasia and endometrial cancer
There have been reports of endometrial hyperplasia (an overgrowth of the lining of the uterus) and endometrial cancer in women taking tibolone (the active substance in Ladybon). The longer the medicine is taken, the higher the risk of endometrial cancer.
Irregular bleeding
During the first 3-6 months of taking Ladybon, irregular bleeding or spotting may occur.
If irregular bleeding:
continues for more than 6 months of treatment,
starts after more than 6 months of taking Ladybon,
continues even after stopping Ladybon,
the patient should consult a 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 the patient takes tibolone. In studies of HRT, it has been found that after stopping HRT, the additional risk decreases over time, but the risk may persist for 10 years or longer if the woman took HRT for more than 5 years.
There is no data on the persistence of risk after stopping tibolone, but it cannot be ruled out that a similar phenomenon may occur.
Comparison
Women taking Ladybon have a lower risk of breast cancer than women taking combined HRT and a similar risk to women taking only estrogen.

• The patient should regularly check their breasts and consult a doctor if they notice any of the following changes:
• Depressions in the skin.
• Changes in the nipples.
• Any visible or palpable lumps.

Ovarian cancer
Ovarian cancer is rare - much rarer than breast cancer. Taking estrogen-only or combined estrogen-progestogen HRT is associated with a slightly increased risk of ovarian cancer.
The risk of developing ovarian cancer changes with age. For example, in women aged 50-54 who do not take HRT, ovarian cancer will be diagnosed in about 2 out of 2000 women over a 5-year period. In women aged 50-54 who take HRT for 5 years, there will be approximately 3 cases per 2000 women (i.e., about 1 additional case).
The increased risk of ovarian cancer with Ladybon is similar to that with other types of HRT.
Effect of HRT on the heart and circulation
Blood clots in the veins (thrombosis)
The risk of blood clots in the veins is about 1.3 to 3 times higher in women taking HRT than in women not taking it, especially in the first year of treatment.
Blood clots can be life-threatening and if a clot moves to the lungs, it can cause chest pain, shortness of breath, fainting, or even death.
The likelihood of blood clots increases with age and if any of the following situations occur. The doctor should be informed if any of the following situations apply to the patient:

• If the patient is pregnant or has recently given birth.
• If the patient is taking estrogens.
• If the patient is unable to walk for a long time due to a major surgical procedure, injury, or illness (see also section 3, "If surgery is necessary").
• If the patient is significantly overweight (BMI >30 kg/m²).
• If the patient has a condition that increases the risk of blood clots, requiring long-term treatment with a medicine to prevent blood clots.
• If any close relatives have had a blood clot in the leg, lung, or other organ.
• If the patient has systemic lupus erythematosus (SLE).
• If the patient has cancer.

Symptoms of a blood clot can be found in "The patient should stop taking Ladybon and consult a doctor immediately".
Comparison
Considering women aged 50-59 who do not take HRT, over a 5-year period, about 4 to 7 out of 1000 women can expect to develop deep vein thrombosis.
In women aged 50-59 who take combined estrogen-progestogen HRT for more than 5 years, about 9 to 12 out of 1000 women can expect to develop deep vein thrombosis (i.e., about 5 additional cases).
While taking Ladybon, the increased risk of deep vein 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 old who take combined estrogen-progestogen HRT, there is a slightly increased risk of heart disease compared to women not taking HRT. Since the risk of heart disease is largely dependent on age, the number of additional cases of heart disease caused by combined estrogen-progestogen HRT is very low in healthy women approaching menopause, but will increase with age.
Stroke
Recent studies suggest that hormonal replacement therapy and tibolone increase the risk of stroke. This increased risk has been observed mainly in women over 60 years old.
Other factors that may increase the risk of stroke include:
Ageing
High blood pressure
Smoking
Excessive alcohol consumption
Irregular heart rhythm
Comparison
Considering women aged 50-59 who do not take tibolone, over a 5-year period, about 3 cases of stroke can be expected per 1000 women.
In women aged 50-59 who take tibolone, the number of cases would be about 7 per 1000 (i.e., 4 additional cases).
Considering women aged 60-69 who do not take tibolone, over a 5-year period, about 11 cases of stroke can be expected per 1000 women.
In women aged 60-69 who take tibolone, the number of cases would be about 24 per 1000 (i.e., 13 additional cases).
Other conditions

• HRT does not prevent memory loss. There is some evidence that starting HRT after the age of 65 may increase the risk of memory loss. The patient should consult a doctor.

Ladybon and other medicines

The doctor or pharmacist should be told about all medicines the patient is taking, has recently taken, or plans to take.
Some medicines may affect the way Ladybon works. This may lead to irregular bleeding. These medicines include:

• Blood-thinning 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

Ladybon can be taken with food and drink.

Pregnancy and breastfeeding

Ladybon is intended only for postmenopausal women. If the patient becomes pregnant, they should stop taking Ladybon and consult a doctor.
Ladybon should not be taken 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 use machines.

Ladybon contains lactose monohydrate

If the patient has been diagnosed with an intolerance to some sugars, they should consult a doctor before taking Ladybon.

3. How to take Ladybon

This medicine should always be taken exactly as prescribed by the doctor or pharmacist. If the patient is unsure, they should consult a doctor or pharmacist.
Ladybon is for oral use. One tablet should be taken once a day. The tablets should be swallowed with a small amount of water or another liquid, preferably at the same time every day.
Ladybon should not be started before at least 12 months after the last natural menstrual period. If Ladybon is started earlier, the risk of irregular bleeding may increase.
To treat symptoms, the doctor will prescribe the lowest possible dose of Ladybon for the shortest possible time. If the patient feels that the dose is too high or too low, they should consult a doctor.

If surgery is necessary

If surgery is necessary, the surgeon should be informed that the patient is taking Ladybon. It may be necessary to stop taking Ladybon about 4 to 6 weeks before the planned operation to reduce the risk of blood clots (see section 2, "Blood clots in the veins"). The patient should consult a doctor to determine when it is possible to restart Ladybon.

Overdose of Ladybon

If the patient takes more Ladybon tablets than prescribed, they should consult a doctor or pharmacist immediately.
There is no reason to worry if the patient takes too many tablets, but they should consult a doctor immediately. Symptoms of overdose include nausea, vomiting, or bleeding from the genital tract.

Missing a dose of Ladybon

If a tablet is missed, it should be taken as soon as possible, unless more than 12 hours have passed since the missed tablet. If more than 12 hours have passed, the missed dose should be skipped.
A double dose should not be taken to make up for a missed dose.

Stopping Ladybon

The patient should not stop taking Ladybon without consulting a doctor.
If the patient has any further questions about taking this medicine, they should consult a doctor or pharmacist.

4. Possible side effects

Like all medicines, Ladybon can cause side effects, although not everybody gets them.
Most symptoms are mild.
The following diseases have been observed more frequently in women taking HRT compared to women not taking HRT:

• Breast cancer.
• Abnormal growth or cancer of the lining of the uterus (endometrial hyperplasia or cancer).
• Ovarian cancer.
• Deep vein thrombosis.
• Heart disease.
• Stroke.
• Possible memory loss if HRT is started after the age of 65. More information about these side effects can be found in section 2.

Other side effects

The following side effects have been reported in clinical trials in women taking tibolone (the active substance in Ladybon):
Common (may affect up to 1 in 10 people):
Spotting or bleeding from the genital tract.
Abdominal pain.
Weight gain.
Breast tenderness.
Unusual hair growth.
Vaginal symptoms, such as itching, discharge, or thrush.
Thickening of the lining of the uterus or cervix.
Uncommon (may affect up to 1 in 100 people):
Swelling of the hands, feet, or ankles - a sign of fluid retention.
Upset stomach.
Acne.
Painful nipples or discomfort in the breasts.
Vaginal infections.
Rare (may affect up to 1 in 1,000 people):
Itching of the skin.
Other side effects reported after tibolone was made available on the market include:

• Dizziness, headaches, migraine, depression.
• Rash.
• Vision disturbances, loss of vision, or blurred vision.
• Pain in the joints or muscles.
• Liver function disorders.
• There have been reports of breast cancer and abnormal growth or cancer of the lining of the uterus in women taking tibolone.
• The doctor should be informed if the patient experiences bleeding or spotting from the genital tract or if any of the above symptoms become troublesome or worsen.
  The following side effects have been observed with other types of HRT:

• Gallbladder disease
• Various skin diseases:
• skin discoloration, especially on the face or neck, known as "pregnancy patches" (chloasma).
• painful red lumps on the skin (erythema nodosum).
• changes in the shape of rings with ulcers (erythema multiforme).

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides: 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
Side effects can also be reported to the marketing authorization holder or its representative in Poland.

5. How to store Ladybon

The medicine should be stored out of sight and reach of children.
The medicine should not be used if any visible signs of deterioration are observed.
The medicine should not be used after the expiry date stated on the packaging after "EXP:". The expiry date refers to the last day of the month.
The medicine should be stored below 25°C. The medicine should be kept in the original packaging to protect it from light and moisture.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Package contents and other information

What Ladybon contains

The active substance of Ladybon is tibolone. Each tablet contains 2.5 mg of tibolone.
Other ingredients are: lactose monohydrate, potato starch, ascorbyl palmitate (E304), magnesium stearate.

What Ladybon looks like and contents of the pack

White or almost white, flat, round tablets with a score line on one side.
Package size: 1×28 or 3×28 tablets.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer:

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

More information about Ladybon

The most important natural sex hormones in women are estrogens and progesterone. They are necessary for normal sexual development and control of the menstrual cycle.
Estrogens are also important for bone formation. Bone is formed in young age and maximum bone mass is reached between the ages of 20 and 30. Then, bone mass decreases, first slowly, but later in life more quickly, especially after menopause. Menopause is the time (usually around the age of 50) when the ovaries gradually stop producing estrogens. If the ovaries are removed surgically before menopause, the decrease in hormone production occurs very quickly.
The decrease in hormone production often causes symptoms such as hot flashes and night sweats. Hormone deficiency can also cause the vaginal lining to become thinner and drier. This can make sexual intercourse painful and increase the risk of vaginal infections. Some women also experience mood changes, nervousness, depression, irritability, and loss of libido.
Often, an unnoticed problem is the faster loss of bone mass in menopausal and postmenopausal women. Bones gradually become brittle and may be prone to fractures (osteoporosis), especially in the spine, hips, and wrists. Osteoporosis can also cause back pain, loss of height, and a hunched back.
Ladybon contains tibolone, a substance that has a beneficial effect on various tissues and organs of the body, such as the brain, vagina, and bones, which helps to alleviate symptoms such as hot flashes and night sweats, and improves the condition of the vaginal lining, mood, and libido. Ladybon may also slow down the loss of bone mass that occurs after menopause in the spine, hips, and wrists. Unlike some hormonal replacement therapies, Ladybon does not affect the lining of the uterus. Therefore, treatment with Ladybon does not cause monthly vaginal bleeding.

For more information about Ladybon and its names in the Member States of the European Economic Area, please contact the representative of the marketing authorization holder in Poland:

Zentiva Poland Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00
Date of last revision of the leaflet:October 2020