Tibelia

PACKAGE LEAFLET

Package leaflet: Information for the patient

Tibelia, 2.5 mg, tablets
Tibolone
Please read the entire leaflet carefully before starting to take this medicine, as it contains
important information for the patient.

• 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 similar.
• If you experience any adverse reactions, inform your doctor or pharmacist. This includes any adverse reactions not listed in this leaflet. See section 4.

Table of contents

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

1. What Tibelia is and what it is used for

Tibelia is a medicine used in Hormone Replacement Therapy (HRT). It contains tibolone – a substance that has beneficial effects on various tissues and organs in the body, including the brain, vagina, and bones.
This medicine is intended for postmenopausal women in whom the last natural menstruation occurred at least 12 months ago.
Tibelia is used in the following cases:

Relief of postmenopausal symptoms
During the perimenopausal period, the amount of estrogen produced by a woman's body decreases. This may cause symptoms such as hot flushes affecting the face, neck, and chest. Tibelia helps relieve postmenopausal symptoms in women. Tibelia is prescribed only when these symptoms significantly interfere with daily life.

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

There are three different types of Hormone Replacement Therapy (HRT):

• Estrogen-only HRT;
• Combined HRT containing two types of female hormones – estrogen and progestagen;
• Tibelia, which contains a substance called tibolone.

Tibelia differs from other HRT treatments. Instead of containing natural hormones (such as estrogen and progestagen), it contains tibolone. The body metabolizes tibolone into hormones.
The action of the medicine and the benefits it provides are similar to those of combined HRT.

2. Important information before using Tibelia

Medical history and regular check-ups
In addition to its benefits, Hormone Replacement Therapy (HRT) carries 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 may differ. This issue should be discussed with your doctor.
Before starting HRT, your doctor should take a full medical history, including any family medical conditions. Your doctor may decide to perform a physical examination, including breast and/or gynecological examination (if necessary).
Inform your doctor about any existing health problems or diseases.

Regular check-ups
After starting Tibelia, regular medical check-ups are necessary (at least once a year). During these visits, the benefits and risks of continuing Tibelia should be discussed with your doctor.
You should attend regular breast examinations as recommended by your doctor.
You should:

• regularly undergo breast examinations and cytological testing;
• regularly examine your breasts for changes such as skin dimpling, changes in the appearance of the nipple, or visible or palpable lumps.

When not to use Tibelia:

• If you are allergic to tibolone or any of the other ingredients of Tibelia (listed in section 6).
• If you currently have, suspect you may have, or have previously had breast cancer.
• If you currently have an estrogen-dependent malignant tumor or suspect you may have one (e.g. endometrial cancer).
• If you have vaginal bleeding of unknown cause.
• If you have excessive growth of the endometrium (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 (within the near past) arterial thrombotic diseases (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 a rare inherited blood disorder called "porphyria".

If you are uncertain about any of the above information, you should consult your doctor before taking Tibelia.
If any of the above conditions occur for the first time while taking Tibelia, you must stop taking the medicine immediately and contact your doctor without delay.

Warnings and precautions
Before taking tibolone, consult your doctor or pharmacist.
In addition to its benefits, HRT carries risks that should be considered when deciding whether to start or continue therapy.
Inform your doctor if you have previously had any of the following conditions, as symptoms may recur or worsen during treatment with Tibelia. In such cases, more frequent check-ups may be necessary:

• uterine fibroids;
• endometriosis (endometrial tissue growth outside the uterus) or previous endometrial hyperplasia (excessive growth of the endometrium);
• increased risk of venous thrombosis (see "Venous thrombosis");
• increased risk of estrogen-dependent tumors (e.g. history of breast cancer in mother, sister, or grandmother);
• hypertension;
• liver diseases, e.g. benign liver tumor;
• diabetes;
• gallstones;
• migraine or severe headaches;
• systemic autoimmune diseases affecting multiple organs (e.g. systemic lupus erythematosus (SLE));
• epilepsy;
• asthma;
• otosclerosis (ear condition leading to hearing impairment);
• very high levels of blood lipids (triglycerides);
• fluid retention due to heart or kidney disease.

When to stop taking Tibelia and contact your doctor immediately
If any of the following conditions occur while taking HRT:

• any of the conditions listed under "When NOT to use Tibelia";
• yellowing of the skin or whites of the eyes (jaundice), which may indicate liver disease;
• increased blood pressure (may present as headache, fatigue, dizziness);
• first occurrence of migraine-type headaches;
• pregnancy;
• symptoms 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 thrombosis".

Note: Tibolone is not a contraceptive. Women under the age of 50 and women whose last menstrual period occurred less than 12 months ago may need to use additional methods of contraception. Consult your doctor for advice.

HRT and malignant tumors

Excessive growth of the endometrium (endometrial hyperplasia) and endometrial cancer
There are reports and studies regarding endometrial hyperplasia or endometrial cancer in women using tibolone. The risk of developing endometrial cancer increases with the duration of therapy.

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

• continues beyond the first 6 months,
• appears after 6 months of starting Tibelia,
• persists after stopping Tibelia, you should contact your doctor as soon as possible.

Breast cancer
Evidence indicates that combined estrogen-progestagen or estrogen-only HRT increases the risk of developing breast cancer. This additional risk depends on the duration of HRT and becomes apparent after several years of treatment, but returns to normal levels within a few years (maximum 5) after stopping treatment.

Comparison
Among women aged 50–79 not using HRT, an average of 9–17 out of 1,000 will develop ovarian cancer within 5 years. Among women aged 50–79 using estrogen-progestagen HRT for 5 years, ovarian cancer will occur in 13–23 out of 1,000 (i.e. 4–6 additional cases).
The risk in women taking tibolone is lower than in women taking combined estrogen-progestagen HRT and comparable to the risk in women taking estrogen-only HRT.

You should regularly perform breast self-examinations. If you notice any changes, contact your doctor. Such changes include:

• skin dimpling;
• changes in the appearance of the nipple;
• any visible or palpable lumps.

Additionally, screening mammograms are recommended. When undergoing a screening mammogram, you must inform the radiographer that you are using HRT, as this medicine may increase breast density, which affects mammogram results. In cases of increased breast density, mammography may not detect all lumps.

Ovarian cancer
Ovarian cancer is rare—much rarer than breast cancer. The use of estrogen-only or combined estrogen-progestagen HRT has been associated with a slight increase in the risk of developing ovarian cancer.
The risk of ovarian cancer depends on age. For example, among women aged 50–54 not using HRT, ovarian cancer will be diagnosed within 5 years in about 2 out of 2,000 women. Among women using HRT for 5 years, about 3 cases per 2,000 will occur (i.e. about 1 additional case).
The increased risk of ovarian cancer with Tibelia is similar to that of other types of HRT.

Effect of HRT on the heart and circulation

Venous thrombosis
The risk of venous thrombosis in women using HRT is approximately 1.3–3 times higher than in women not using 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, shortness of breath, fainting, or even death.
The likelihood of venous clot formation increases with age and in the presence of the following risk factors, which should be discussed with your doctor (if applicable):

• 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 > 30 kg/m²);
• any blood clotting disorders requiring long-term anticoagulant treatment;
• history of blood clots in legs, lungs, or other organs in any family member;
• systemic lupus erythematosus (SLE);
• malignant tumor.

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

Comparison
It is estimated that among women aged 50–59 not using HRT, venous thrombosis will occur in an average of 4–7 out of 1,000 within 5 years.
Among women of the same age using estrogen-progestagen HRT for 5 years, this figure will be 9–12 out of 1,000 (i.e. 5 additional cases).
When using tibolone, 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 prevents myocardial infarction.
In women over 60 using estrogen-progestagen HRT, there is a slightly higher likelihood of developing heart disease compared to women not using HRT.
There are no data indicating that the risk of myocardial infarction during tibolone use differs from that associated with other types of HRT.

Stroke
The risk of stroke in women using HRT or tibolone is approximately 1.5 times higher than in women not using these medicines. The number of additional stroke cases associated with HRT use will increase with age.
Other factors that may increase stroke risk:

• hypertension;
• smoking;
• alcohol abuse;
• cardiac arrhythmias.
  Individuals concerned about any of these factors should consult their doctor to determine whether they should use HRT.

Comparison
It is estimated that among women aged 50–59 not using HRT, stroke will occur in an average of 8 out of 1,000 within 5 years. Among women of the same age using HRT for 5 years, this figure will be 11 out of 1,000 (i.e. 3 additional cases).

Other conditions
HRT does not prevent memory loss. Some data suggest a higher risk of memory loss in women who start HRT after age 65. Consult your doctor for advice.
Tibelia is not intended for use as a contraceptive.
Estrogens may cause fluid retention, so patients with heart or kidney failure should remain under close medical supervision.
Women with pre-existing hypertriglyceridemia should be closely monitored during estrogen supplementation or HRT, as rare cases of significant increases in serum triglyceride levels leading to pancreatitis have been observed in patients treated with estrogens under these circumstances.

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

• antiepileptic drugs (e.g. phenobarbital, phenytoin, carbamazepine);
• antituberculosis drugs (e.g. rifampicin, rifabutin);
• HIV drugs (e.g. nevirapine, efavirenz, ritonavir, nelfinavir);
• anticoagulants (e.g. warfarin);
• herbal products containing St. John's wort (Hypericum perforatum).

Inform your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take, including over-the-counter medicines, herbal products, and other natural supplements.

Laboratory tests
Before undergoing blood tests, inform your doctor or laboratory staff that you are taking Tibelia, as it may affect the results of certain tests.

Tibolone with food and drink
Eating and drinking do not affect the administration of Tibelia.

Pregnancy, breastfeeding, and fertility
Tibelia is intended for use only in postmenopausal women. If pregnancy occurs, stop taking Tibelia and consult your doctor.

Driving and operating machinery
According to current data, tibolone does not affect alertness or concentration.

Tibelia contains lactose
Each tablet contains 43.2 mg of monohydrate lactose. If you have been diagnosed with intolerance to certain sugars, consult your doctor before taking this medicinal product.

3. How to use Tibelia

Always take this medicine exactly as prescribed by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.
It is recommended to take one tablet daily.
Swallow the tablet whole, without chewing, with water.
Take the tablet at the same time each day.
Blister packs are labeled with days of the week. Begin treatment by taking the tablet marked with the correct day. For example, if the first tablet is taken on Monday, take the tablet labeled "Mon" in the top row of the pack and continue taking tablets each day of the week until the pack is empty. Take the first tablet from the next blister pack the following day, without any break between blister packs or packs.

Your doctor will prescribe the lowest effective dose for the shortest possible duration to treat your symptoms. If the dose seems too strong or too weak, consult your doctor.

In cases of natural menopause, tibolone should not be used until at least 12 months have passed since the last menstrual bleeding.

Women who have had their uterus and ovaries removed, or who are taking gonadotropin-releasing hormone analogs (GnRH), e.g. due to endometriosis, may start taking tibolone immediately.

Women who have never used HRT may start taking tibolone immediately.

Women switching from another type of HRT
There are several types of HRT, e.g. tablets, patches, and gels. Most contain estrogen or estrogen and progestagen. Some HRT regimens cause bleeding, while others do not.
If switching from an HRT regimen that causes bleeding, start taking tibolone immediately after the bleeding ends.
If switching from an HRT regimen that does not cause bleeding, tibolone may be started immediately. Women being treated for endometriosis may also start taking the medicine immediately.

Use in children and adolescents
Tibolone should not be used in children.

Taking more Tibelia than recommended
If several tablets are taken at once, there is generally no cause for concern, but symptoms of overdose may include nausea, vomiting, or vaginal bleeding.

Missed dose
Take the missed tablet as soon as possible, unless more than 12 hours have passed since the scheduled time. If more than 12 hours have passed, skip the missed dose and take the next dose at the usual time.
Do not take a double dose

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

Stopping tibolone
Do not stop taking tibolone without first consulting your doctor, even if you feel better. Continue taking the medicine for as long as your doctor recommends; otherwise, symptoms may return.
If you have further questions about using this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Compared to women not using HRT, the following diseases are more frequently observed in women undergoing such therapy:

• Breast cancer;
• Abnormal growth or cancer of the uterine lining (endometrial hyperplasia or endometrial cancer);
• Ovarian cancer;
• Venous thrombosis in the legs and lungs (venous thromboembolic disease);
• Heart diseases;
• Stroke;
• Possible memory loss when HRT is initiated after the age of 65.

For further information on the above adverse effects – see section 2.
Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Most adverse effects are mild in nature.
Serious adverse effects – requiring immediate contact with a doctor
If symptoms of a serious adverse effect occur, contact a doctor immediately.
Discontinuation of Tibelia may be necessary if any of the following occur:

• Increase in blood pressure;
• Yellowing of the skin or whites of the eyes ( jaundice);
• Sudden onset of migraine-type headaches (see section 2 above);
• Symptoms of thrombosis (see section 2 above);
• Any of the problems listed in section 2 (When not to use Tibelia).

Other adverse effects
Common (occur in up to 1 in 10 women):

• Breast pain;
• Abdominal or pelvic pain;
• Excessive or unusual hair growth;
• Vaginal bleeding or spotting. (This symptom is usually not a cause for concern during the first few months of HRT use; if bleeding persists or occurs after a long period of HRT use, see section 2 "Irregular bleeding");
• Vaginal problems such as excessive discharge, itching, or irritation;
• Vulvovaginitis;
• Vaginal candidiasis;
• Thickening of the endometrial layers (lining of the uterus);
• Changes in cervical tissue;
• Abnormal cervical smear;
• Weight gain.

Uncommon (occur in up to 1 in 100 women):

• Swelling of the hands, ankles, or feet (sign of fluid retention);
• Gastrointestinal problems;
• Acne;
• Nipple pain or breast discomfort;
• Vaginal infections (fungal);
• Fungal infections.

Rare (occur in up to 1 in 1,000 women):

• Skin itching.

Other adverse effects reported by women taking Tibelia:

• Depression, dizziness, headaches;
• Joint or muscle pain;
• Skin problems such as rash or itching;
• Impaired vision or blurred vision;
• Changes in liver function test results. Cases of breast cancer and excessive endometrial growth or cancer of the uterine lining have been reported in women using Tibelia. If any of the above adverse effects persist or become troublesome, inform your doctor.

The following adverse effects have been reported during use of other HRT products:

• Gallbladder diseases;
• Various skin disorders;
• Skin pigmentation, particularly on the face or neck (chloasma);
• Painful red nodules on the skin (erythema nodosum);
• Rash involving circular red patches or blisters (erythema multiforme).

Reporting of adverse effects
If any adverse effects occur, inform your doctor or pharmacist. This includes any adverse effects not listed in this leaflet. Adverse effects can also be reported directly via the national reporting system:
Department for Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
PL-02 222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
e-mail: [email protected]
Adverse effects can also be reported directly to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store Tibelia

Keep the medicine out of sight and reach of children.
This medicinal product does not require any special temperature conditions during storage.
Store in the original packaging to protect from light and moisture.
Do not use the medicine after the expiry date stated on the blister and carton following the abbreviation "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. Such measures help protect the environment.

6. Contents of the package and other information

What Tibelia contains

• The active substance is tibolone.
• The other ingredients are: lactose monohydrate (see section 2. "Tibelia contains lactose"), mannitol, potato starch, ascorbyl palmitate, and magnesium stearate.

What Tibelia looks like and contents of the pack
Tibelia is a white or almost white, round tablet, 6 mm in diameter, with a bevelled edge and no markings.
Each package contains 1, 3 or 6 blisters with 28 or 30 tablets each.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
NOVALON S.A
rue Saint-Georges 5
4000 Liege
Belgium

Manufacturer
Cenexi
rue de Pontoise 17
95520 Osny
France

This medicinal product is authorised in the EEA Member States under the following names:
Finland   Tibelia 2.5 mg tablets
Greece    Tibelia 2.5 mg tablets
Norway    Tibelia
Poland     Tibelia
Portugal   Tibelia 2.5 mg Comprimido
Sweden    Tibelia 2.5 mg Tablet
Hungary   Tibelia 2.5 mg tabletta
Italy       Shyla
United Kingdom Tibolone-Mithra 2.5 mg Tablet