Package leaflet: Information for the user

Tibolone Aristo, 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, please ask your doctor or pharmacist.
This medicine has been prescribed for you personally. Do not pass it on to others. It may harm someone else even if their symptoms are the same as yours.
If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Contents of the leaflet

What Tibolone Aristo is and what it is used for
Important information before taking Tibolone Aristo
How to take Tibolone Aristo
Possible side effects
How to store Tibolone Aristo
Contents of the pack and other information

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

Tibolone Aristo is used in hormone replacement therapy (HRT). It contains tibolone, a synthetic sex hormone. Tibolone Aristo is used in postmenopausal women, in whom at least 12 months have passed since the last natural menstrual period.

Tibolone Aristo is used to:
Relieve symptoms occurring after menopause.
During 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. Tibolone Aristo relieves these postmenopausal symptoms. Tibolone Aristo will be prescribed only when these symptoms significantly interfere with the patient's daily life.

2. Important information before taking Tibolone Aristo

Medical history and regular check-ups
Hormone replacement therapy (HRT) or the use of Tibolone Aristo carries risks that should be evaluated before deciding to start or continue treatment.
Experience in treating women with premature menopause (due to ovarian failure or surgical intervention) is limited. In cases of premature menopause, the risks associated with HRT or Tibolone Aristo may differ. This should be discussed with your doctor.
Before starting (or restarting) HRT or Tibolone Aristo, your doctor will take a detailed medical history, including your personal health status and family medical conditions. Your doctor may decide to perform a physical examination, which could include a breast examination and/or a gynaecological examination.
After starting Tibolone Aristo, you must attend regular check-up visits with your doctor (at least once a year). During these visits, the benefits and risks of continuing Tibolone Aristo should be reviewed.
You should regularly examine your breasts as advised by your doctor.
Additionally, you should undergo regular breast screening examinations (mammography). Before undergoing a mammogram, it is important to inform the radiology technician that you are receiving hormone replacement therapy, as this medication may increase breast density, which can affect the interpretation of mammographic images. Increased breast density may mean that some lumps are not detected by mammography.

When not to take Tibolone Aristo
If any of the following conditions apply to you, or if you have any doubts about the points listed below, you must consult your doctor before taking Tibolone Aristo:

If you have or have previously had breast cancer, or if breast cancer is suspected.
If you have an estrogen-dependent tumour, e.g. endometrial cancer (cancer of the lining of the uterus), or if such a tumour is suspected.
If you have vaginal bleeding of unknown cause.
If you have excessive growth of the endometrial lining (endometrial hyperplasia) that is untreated.
If you have or have previously had blood clots in the veins (venous thromboembolism), e.g. in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism).
If you have blood clotting disorders (e.g. protein C, protein S or antithrombin deficiency).
If you have or have previously had arterial diseases caused by blood clots, such as: myocardial infarction, stroke, or angina pectoris.
If you have liver disease and liver function test results have not returned to normal.
If you have a rare inherited blood disorder called porphyria.
If you are allergic to tibolone or any of the other ingredients of Tibolone Aristo (listed in section 6).
If you are pregnant or suspect you may be pregnant.
If you are breastfeeding.

If any of the above conditions occur for the first time during treatment with Tibolone Aristo, the medication should be stopped immediately and discussed with your doctor without delay.

Warnings and precautions
Before starting Tibolone Aristo, discuss this with your doctor or pharmacist.
Before starting treatment, inform your doctor if you have ever experienced any of the following conditions, as they may recur or worsen during treatment with Tibolone Aristo. In such cases, your doctor may recommend more frequent check-ups:

Uterine fibroids
Presence of endometrial tissue outside the uterus (endometriosis) or history of endometrial hyperplasia
Increased risk of venous thromboembolism [see "Blood clots in the veins (thrombosis)"]
Increased risk of estrogen-dependent cancer (e.g. breast cancer in mother, sister or grandmother)
High blood pressure
Liver disease, e.g. benign liver tumour
Diabetes
Gallstones
Migraine or severe headaches
Autoimmune disease affecting multiple organs (systemic lupus erythematosus – SLE)
Epilepsy
Bronchial asthma
Disease affecting the middle ear and hearing (otosclerosis)
Very high levels of blood fats (triglycerides)
Heart disease
Kidney disease

Stop taking Tibolone Aristo and contact your doctor immediately if any of the following occur during HRT or treatment with Tibolone Aristo:

Any of the conditions listed under "When not to take Tibolone Aristo"
Yellowing of the skin or whites of the eyes (jaundice) – these may be symptoms of liver disease
Significant increase in blood pressure (symptoms include: headaches, fatigue, dizziness)
First occurrence of migraine-type headache
If pregnancy occurs
If symptoms of thrombosis occur, such as:
- Painful swelling and redness in the lower limbs
- Sudden chest pain
- Difficulty breathing

For more information, see section "Blood clots in the veins (thrombosis)".

Note: Tibolone Aristo is not a contraceptive. If less than 12 months have passed since your last menstrual period, or if you are under 50 years of age, additional contraception may still be necessary to prevent pregnancy. Consult your doctor for advice.

HRT and cancer
Excessive thickening of the uterine lining (endometrial hyperplasia) and endometrial cancer
Observational studies have clearly shown that women using tibolone (the active substance in Tibolone Aristo) have an increased risk of developing uterine cancer. This risk increases with longer duration of treatment.

Irregular bleeding
Irregular bleeding or spotting may occur during the first 3–6 months of taking Tibolone Aristo. However, if bleeding or spotting:

Persists beyond the first 6 months of treatment
Begins after you have been taking Tibolone Aristo for more than 6 months
Continues after stopping Tibolone Aristo
→ You should contact your doctor immediately.

Breast cancer
Data confirm that taking tibolone increases the risk of developing breast cancer. The additional risk depends on the duration of tibolone use. Studies on HRT have shown that after stopping HRT, the additional risk decreases over time, but may persist for 10 years or longer if HRT was used 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 Tibolone Aristo have a lower risk of developing breast cancer than women taking combined HRT, and a comparable risk to women taking estrogen-only therapy.

Breast examinations should be performed regularly. Contact your doctor if you notice any of the following changes:

Dimpling of the skin
Changes in the nipple
Any visible or palpable lumps

Ovarian cancer
Ovarian cancer is rare – much less common than breast cancer. The use of estrogen-only HRT or combined estrogen-progestagen HRT has been associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer increases with age. For example, among women aged 50–54 years not using HRT, about 2 in 2,000 women will be diagnosed with ovarian cancer over a 5-year period. Among women taking HRT for 5 years, about 3 in 2,000 women will be diagnosed (i.e. about 1 additional case).
During treatment with Tibolone Aristo, the increased risk of ovarian cancer is similar to that associated with other types of HRT.

Effects of HRT on the heart and circulatory system
Blood clots in the veins (thrombosis)
The risk of venous blood clots is approximately 1.3 to 3 times higher in women using HRT than in women not using HRT, especially during the first year of treatment.
Venous 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 a venous clot increases with age and if any of the following conditions apply to you. Inform your doctor if any of the following apply:

If you are taking estrogens
If you are unable to move for prolonged periods due to major surgery, injury, or illness (see also section 3 "If surgery is required"). The risk of thromboembolic disease may be temporarily increased by prolonged immobilisation (e.g. due to severe illness or a leg in plaster), serious trauma, or long surgical procedures. In women using HRT, as in all patients, preventive measures to avoid venous thromboembolism should be carefully followed.
If you are significantly overweight (BMI >30 kg/m²)
If you have clotting disorders requiring long-term anticoagulant therapy
If you have a close relative who has had a blood clot in the leg, lung, or another organ
If you have systemic lupus erythematosus (SLE)
If you have cancer

Symptoms of blood clots are described in the section "Stop taking Tibolone Aristo and contact your doctor immediately".

Comparison
Among women over 50 years of age not taking HRT, 4 to 7 out of 1,000 women can be expected to develop venous thrombosis over 5 years.
Among women over 50 years of age taking combined estrogen-progestagen HRT for more than 5 years, this number increases to 9 to 12 out of 1,000 women (i.e. 5 additional cases).
During treatment with Tibolone Aristo, the increased risk of venous thrombosis is lower than with other types of HRT.

Heart disease (myocardial infarction)
There is no evidence that HRT or Tibolone Aristo prevents heart attacks.
In women over 60 years of age taking combined estrogen-progestagen HRT, the likelihood of developing heart disease is slightly higher than in women not taking HRT. Since the risk of heart disease strongly depends on age, the number of additional cases is very small in healthy women shortly after menopause but increases with age.
There is no evidence that the risk of myocardial infarction during tibolone use differs from that observed with other types of HRT.

Stroke
The risk of stroke is 1.5 times higher in women using HRT than in women not using HRT. The number of additional stroke cases due to HRT use increases with age.

Comparison
Among women over 50 years of age not taking tibolone, about 3 in 1,000 women can be expected to have a stroke over 5 years.
Among women over 50 years of age taking tibolone, this number increases to 7 in 1,000 women (i.e. 4 additional cases).
Among women over 60 years of age not taking tibolone, about 11 in 1,000 women can be expected to have a stroke over 5 years.
Among women over 60 years of age taking tibolone, this number increases to 24 in 1,000 women (i.e. 13 additional cases).

Other conditions
HRT does not prevent memory loss. Some data suggest an increased risk of memory loss in women who start HRT after age 65. Consult your doctor.
Tibolone treatment causes changes in cholesterol levels.
Women with heart or kidney dysfunction: estrogens may cause fluid retention, so women with heart or kidney disorders should be closely monitored.
Women with lipid metabolism disorders (hypertriglyceridemia): women with previously diagnosed hypertriglyceridemia should be closely monitored during tibolone treatment, as rare cases of significant increases in serum triglyceride levels leading to pancreatitis have been reported during estrogen therapy.

Tibolone Aristo and other medicines
Some medicines may affect the action of Tibolone Aristo, potentially causing irregular bleeding. These include:

Medicines that prevent blood clotting (e.g. warfarin)
Medicines used for epilepsy (e.g. phenobarbital, phenytoin, carbamazepine)
Medicines used for tuberculosis (e.g. rifampicin or rifabutin)
Herbal products containing St John’s wort (Hypericum perforatum)

HRT may also affect the action of certain other medicines:

Concomitant use of anticoagulants and tibolone may enhance their anticoagulant effect.
Concomitant use with tibolone may affect the action of medicines containing active substances (e.g. midazolam) that are metabolised by specific enzymes (cytochrome P450 enzymes).

Inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, including over-the-counter medicines, herbal remedies, natural products, and any medicines you plan to take. Your doctor will advise you accordingly.

Laboratory tests
If blood tests are required, inform your doctor or laboratory staff that you are taking Tibolone Aristo, as this medicine may affect the results of certain tests.

Pregnancy and breastfeeding
Do not take Tibolone Aristo during pregnancy or while breastfeeding.
Tibolone Aristo is intended for use only in postmenopausal women. If you become pregnant, stop taking Tibolone Aristo and contact your doctor immediately.

Driving and operating machinery
Tibolone Aristo has no effect on the ability to drive or operate machinery.

Tibolone Aristo contains monohydrate lactose
If you have previously been diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicine.

3. How to take Tibolone Aristo

This medicine should always be taken as directed by the doctor. If in doubt, consult
the doctor or pharmacist.
What dose of Tibolone Aristo should be taken and how often
To treat symptoms, the doctor will prescribe the lowest effective dose for the shortest possible
duration. If the patient feels the medicine is too strong or too weak, she should consult the doctor.
Unless otherwise directed by the doctor, the usual dose is one tablet daily after a meal,
preferably taken at the same time each day.
During treatment with Tibolone Aristo, do not take medicines containing progestogens.
How to take Tibolone Aristo
Tablets should be taken with a small amount of water or another drink, preferably at the same time
each day.
What to consider before starting Tibolone Aristo
If menopause occurred naturally, treatment with Tibolone Aristo should be started no earlier than
1 year after the last natural menstrual period. If the ovaries have been surgically removed,
treatment with Tibolone Aristo may be started immediately.
If a patient wishes to start taking Tibolone Aristo and has irregular or unexpected vaginal bleeding,
she should consult her doctor to exclude malignancy before starting treatment with Tibolone Aristo.
If a patient wishes to switch from a medicine containing estrogen and progestagen to Tibolone Aristo,
she should consult her doctor about what should be done in such a situation.
How long to take Tibolone Aristo
The doctor will choose the shortest possible treatment duration.
Symptoms usually improve within a few weeks.
Taking more Tibolone Aristo than recommended
If more than the recommended dose of Tibolone Aristo has been taken, contact a doctor or pharmacist
immediately.
Toxic effects are unlikely, even if the patient has taken several tablets at once. In case of acute
overdose, symptoms may include nausea, vomiting, and withdrawal bleeding. Contact a doctor for
treatment of these symptoms.
If a dose of Tibolone Aristo is missed
If the patient forgets to take the tablet at the usual time, she should take it as soon as possible,
provided that less than 12 hours have passed since the scheduled time of intake.
If more than 12 hours have passed, the missed tablet should be skipped and the next tablet taken
at the usual time. Do not take a double dose to make up for a missed tablet.
If surgery is required
If the patient is scheduled for surgery, inform the surgeon about taking Tibolone Aristo.
It may be necessary to discontinue Tibolone Aristo approximately 4 to 6 weeks before surgery to
reduce the risk of venous thrombosis [see section 2 "Blood clots in the veins (thrombosis)"].
Ask the doctor when it will be safe to restart taking Tibolone Aristo.
If there are any further doubts regarding the use of Tibolone Aristo, consult the doctor or pharmacist.

4. Possible adverse effects

The following diseases have been reported 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
presence of blood clots in the veins of the legs or lungs (venous thromboembolic disease)
heart disease
stroke
possible memory loss if HRT is started after the age of 65.
For more information about these adverse effects, see section 2 "Important information before taking Tibolone Aristo".
Like all medicines, Tibolone Aristo may cause adverse effects, although not everyone experiences them.
Patients should inform their doctor or pharmacist if they have any concerns about adverse effects they think may be related to taking Tibolone Aristo; see also section 2 "Stop taking Tibolone Aristo and contact your doctor immediately".
Commonly occurring adverse effects observed in clinical trials (affecting up to 1 in 10 women):
vaginal bleeding or spotting
abdominal pain
weight gain
breast pain
excessive hair growth
vaginal problems, e.g. increased discharge, itching and irritation
thickening of the uterine lining
fungal vaginal infection (e.g. candidiasis)
pelvic pain
changes in the cervical tissue
inflammation of the labia and vagina (so-called vulvovaginitis)
abnormalities in cytological smear tests.
Uncommon adverse effects (affecting up to 1 in 100 women):
acne
tenderness of nipples or breasts
fungal infections.
Other adverse effects reported after tibolone has been placed on the market:
dizziness, headache, migraine
depression
skin problems, e.g. rash or itching
vision loss or blurred vision
gastrointestinal disturbances
fluid retention
joint or muscle pain
changes in liver function parameters.
Cases of uterine cancer, breast cancer and stroke have been reported in women taking tibolone (see section 2 "Warnings and precautions").
The following adverse effects have been reported with the use of other types of HRT:
gallbladder disease
various skin disorders:
skin pigmentation, particularly on the face or neck, known as chloasma (melasma)
painful red skin nodules (erythema nodosum)
ring-shaped rash with redness or erosions (erythema multiforme)
subcutaneous bleeding (purpura).
Patients should inform their doctor about irregular vaginal bleeding or spotting, or about the occurrence or worsening of any of the adverse effects listed above.
Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, patients should inform their doctor or pharmacist. Adverse effects can be reported directly to the Department of 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 4921301; fax: +48 22 4921309
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 Tibolone Aristo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton/blister pack.
EXP: The expiry date refers to the last day of the specified month.
There are no special storage requirements for this medicine.
Do not use this medicine if blister pack damage is visible.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the package and other information

What Tibolone Aristo contains

The active substance is tibolone. One tablet contains 2.5 mg of tibolone.
The other ingredients are: Monohydrate lactose, potato starch, ascorbyl palmitate, magnesium stearate.

What Tibolone Aristo looks like and contents of the pack
Tibolone Aristo is white or almost white, flat, round tablets with a diameter of approximately 6 mm.
Tibolone Aristo is available in packs containing 1 x 28 tablets, 1 x 30 tablets, and 3 x 28 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Aristo Pharma Sp. z o.o.
ul. Baletowa 30
02-867 Warsaw
Poland

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

This medicinal product is authorised in the European Economic Area countries and in the United Kingdom (Northern Ireland) under the following names:
Spain: Tibolona Aristo 2.5 mg comprimidos EFG
Germany: Tibolon Aristo 2.5 mg Tabletten
Belgium: Tibolone Aristo 2.5 mg tabletten/comprimés/Tabletten
Italy: Tibolone Aristo
United Kingdom: Tibolone 2.5 mg tablets
Czech Republic: Tibolon Aristo
Ireland: Tibolone Aristo 2.5 mg tablets
Poland: Tibolone Aristo
Slovakia: Tibolónu Aristo 2.5 mg tablety
Sweden: Tibolon Oresund Pharma 2.5 mg tabletter
Norway: Tibolon Oresund Pharma 2.5 mg tabletter
Finland: Tibolon Aristo 2.5 tabletit

Tibolone aristo