TIBICARE 2.5 mg TABLETS

2. What you need to know before you start taking Tibicare 2.5 mg Tablets

Medical history and regular medical check-ups

Hormone Replacement Therapy (HRT) involves risks that need to be considered when deciding whether to start or continue HRT.

Treatment experience in women with premature menopause (due to an ovarian problem or surgical operation) is limited. If you have premature menopause, the risk of using HRT may be different. Consult your doctor.

Before starting or continuing treatment with HRT, your doctor will assess your personal and family medical history and may decide to perform a medical examination, including a breast examination and/or internal examination if necessary.

Tell your doctor if you have any medical problems or illnesses.

Regular medical check-ups

Once you have started treatment with tibolone, you should visit your doctor for regular medical check-ups (at least once a year). During these check-ups, the benefits and risks of continuing treatment with tibolone will be assessed.

Your doctor may recommend that you have regular mammograms.

Make sure that:

• you have regular breast and cervical screening tests
• you regularly check your breasts for changes, such as dimpling of the skin, changes in the nipple, or any lumps that you can see or feel.

Do not take Tibicare

• if you have or have had breast canceror if you suspect you might have it,
• if you have any type of estrogen-sensitive cancer, such as endometrial cancer or if you suspect you might have it,
• if you have unexplained vaginal bleeding
• if you have unusual growth of the lining of the womb (endometrial hyperplasia)that has not been treated,
• if you have or have had a blood clot (thrombosis)in your legs (deep vein thrombosis) or lungs (pulmonary embolism)
• if you have or have had any blood clotting problems(such as protein C, protein S, or antithrombin deficiency).
• if you have or have had any arterial disease(such as a heart attack, stroke, or angina)
• if you have or have had any liver diseaseand your liver function has not returned to normal,
• if you have a rare inherited blood disordercalled porphyria,
• if you are allergicto the active substance or any of the other ingredients of this medicine (listed in section 6)

If you are not sure about any of the above, consult your doctorbefore taking tibolone.

If you experience any of the conditions mentioned above for the first time while taking tibolone, stop taking it immediately and consult your doctor.

Warnings and precautions

Consult your doctor or pharmacist before starting to take tibolone.

HRT has some risks and benefits that need to be considered before deciding to start or continue HRT.

Consult your doctor if you have or have had any of the following problems, before starting treatment, as they may come back or get worse during treatment with tibolone. If so, you may need to have more frequent check-ups:

• Fibroids in the womb
• Unusual growth of the lining of the womb (endometriosis) or a history of unusual growth of the lining of the womb (endometrial hyperplasia).
• A high risk of blood clots (see "Blood clots in a vein (thrombosis)").
• A high risk of estrogen-dependent cancer (such as if your mother, sister, or grandmother has had breast cancer).
• High blood pressure.
• Liver disease, such as a benign liver tumor.
• Diabetes.
• Gallstones.
• Migraine or severe headaches.
• A disease that affects the immune system and various organs of the body (systemic lupus erythematosus (SLE))
• Epilepsy.
• Asthma.
• A disease that affects the eardrum and hearing (otosclerosis).
• Very high levels of fat in the blood (triglycerides).
• Fluid retention due to heart or kidney problems.

Stop taking Tibicare and consult your doctor immediately

If you are taking HRT and experience any of the following symptoms, such as:

• any of the conditions mentioned in the section "Do not take Tibicare";
• yellowing of the skin and eyes (jaundice). This could be a sign of liver disease;
• a significant increase in blood pressure (symptoms may be headache, fatigue, dizziness).
• unexplained migraine-like headaches that appear for the first time.
• if you become pregnant.
• If you notice symptoms of a possible blood clot, such as:
• • swelling and redness in the legs
  • sudden chest pain
  • difficulty breathing

For more information, see "Blood clots in a vein (thrombosis)".

Note:Tibicare is not a contraceptive. If it has been less than 12 months since your last natural period or you are under 50 years old, you should use a contraceptive method to prevent pregnancy. Consult your doctor for advice.

HRT and cancer

Unusual growth of the lining of the womb (endometrial hyperplasia) and cancer of the lining of the womb (endometrial cancer)

There is evidence of an increased risk of unusual cell growth or cancer of the lining of the womb in women taking tibolone. This risk increases with the duration of treatment.

Irregular bleeding

You may experience irregular bleeding or spotting during the first 3 to 6 months of treatment with tibolone. However, if the bleeding or spotting:

• lasts longer than the first 6 months
• starts after you have been taking tibolone for more than 6 months.
• continues after you have stopped taking tibolone

consult your doctor immediately.

Breast cancer

Existing data shows that the use of tibolone increases the risk of breast cancer. The additional risk depends on the duration of treatment with tibolone. In studies with HRT, after stopping HRT, the additional risk decreased over time, but the risk may persist for 10 years or more in women who have used HRT for more than 5 years. There is no data available on the persistence of risk after stopping tibolone, but a similar pattern cannot be ruled out.

Examine your breasts regularly. Consult your doctor if you notice any changes, such as:

• formation of dimples in the skin
• changes in the nipple
• any lumps that you can see or feel

In addition, it is recommended to participate in early detection programs through mammography. It is essential to inform the healthcare professional performing the mammography that you are taking HRT, as this medicine may increase the density of your breasts and affect the test results. When breast density is increased, mammography may not detect lumps.

Ovarian cancer

Ovarian cancer is rare, much less common than breast cancer. There is a slight increase in the risk of ovarian cancer in women taking HRT with estrogen only or combined estrogen-progestogen.

The risk of ovarian cancer varies with age. In women aged 50 to 54 who do not take HRT, on average, 2 out of 2000 women will have ovarian cancer over a 5-year period. In women who do not take HRT for 5 years, on average, 3 cases of ovarian cancer will occur per 2000 women (1 additional case).

The risk of ovarian cancer with tibolone is similar to the risk with other types of HRT.

Effects of HRT on the heart and circulation

Blood clots in a vein (thrombosis)

The risk of having a blood clot in a vein is 1.3 to 3 times higher in patients taking HRT than in women not taking HRT, especially during the first year of treatment.

Blood clots can be serious and if one reaches the lungs, it can cause chest pain, difficulty breathing, fainting, and even death.

You are more likely to have a higher risk of a blood clot in your veins as you get older and if you are affected by any of the following conditions:

• if you are unable to walk for a long time due to a major operation, injury, or illness (see also section 3, If you need to have surgery)
• if you are significantly overweight (BMI >30 kg/m2)
• if you have blood clotting problems that require long-term treatment with a medicine to prevent clots
• if any of your close relatives have had a blood clot in their leg, lung, or other organ
• if you have systemic lupus erythematosus (SLE)
• if you have cancer

Tell your doctor if you experience any of these conditions.

To identify the symptoms of a blood clot, see "Stop taking Tibicare and consult your doctor immediately".

Heart disease (heart attack)

There is no evidence that HRT or tibolone can prevent a heart attack.

There is a slight increase in the risk of heart disease in women over 60 who take combined estrogen-progestogen HRT compared to those who do not take HRT.

There is no evidence to suggest that the risk of heart attack with tibolone is different from the risk with other HRTs.

Stroke

The risk of having a stroke is 1.5 times higher in patients taking HRT than in those not taking HRT. The risk due to HRT increases with age. The number of additional stroke cases due to HRT increases with the patient's age.

Other situations that may increase the risk of stroke are:

• high blood pressure
• smoking
• excessive alcohol consumption
• irregular heartbeat

If you are concerned about any of these situations, consult your doctor if you should take HRT.

Other diseases

HRT does not prevent memory loss. Some evidence suggests a higher risk of memory loss in women who start HRT after the age of 65. Consult your doctor for more information.

Tibicare is not a contraceptive.

Estrogens may cause fluid retention, and caution is needed in patients with heart or kidney disease.

Special monitoring is needed for patients with high triglycerides, as estrogen or HRT use has been associated with high increases in triglycerides in the blood, which can cause pancreatitis.

Using Tibicare with other medicines

Some medicines may interfere with the effect of Tibicare. This may cause irregular bleeding. These medicines include:

• medicines used to treat epilepsy (e.g., phenobarbital, phenytoin, and carbamazepine),
• medicines used to treat tuberculosis (e.g., rifampicin or rifabutin)
• medicines used to treat HIV (e.g., nevirapine, efavirenz, ritonavir, and nelfinavir),
• medicines used to treat blood clots (e.g., warfarin),
• herbal remedies containing St. John's Wort (Hypericum perforatum),

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.

Lab tests

If you need to have a blood test, tell your doctor or the laboratory staff that you are taking tibolone, as this medicine may affect the results of some tests.

Taking Tibicare with food and drink

You can eat and drink normally while taking Tibicare.

Pregnancy, breastfeeding, and fertility

Tibicare is only indicated for postmenopausal women. If you become pregnant, stop taking Tibicare and consult your doctor.

Driving and using machines

There is no information to suggest that taking Tibicare affects your ability to drive or use machines.

Tibicare contains lactose

This medicine contains 43.2 mg of lactose monohydrate per tablet. If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to take Tibicare 2.5 mg EFG tablets

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The recommended dose is one tablet per day.

You should swallow the tablet, without chewing, with a little water.

Take the tablet every day at the same time.

The strips of the tablets are marked with the days of the week. Start taking the tablet on the day that corresponds. For example, if it is Monday, take the tablet marked with "M" at the beginning of the strip. Follow the arrows until the strip is finished. The next day, start the next strip.

Your doctor will try to prescribe you the lowest dose to treat your symptoms for the shortest possible time. Consult your doctor if you think your dose is too strong or too weak.

You should not take tibolone until 12 months have passed since your last natural period.

If you have had your ovaries and uterus removed or are being treated for endometriosis with gonadotropin-releasing hormone (GnRH) analogs, you can start taking tibolone immediately.

If you have never used HRT before,you can start treatment immediately.

If you are changing from another type of HRT

There are different types of HRT, such as tablets, patches, and gels. Most contain estrogens or estrogens with progestogens. Some have bleeding between cycles (sequential preparations) and others do not (continuous regimen).

If you were taking a sequential preparation, you should start taking tibolone immediately after the bleeding finishes.

If you were taking a continuous regimen preparation (without bleeding), you can start taking tibolone at any time. You can also start taking tibolone immediately if you are being treated for endometriosis.

Use in children and adolescents

Tibolone should not be administered to children.

If you take more Tibicare than you should

It is unlikely that you will suffer any harm if you take more than one tablet, but the symptoms may include nausea, vomiting, or vaginal bleeding.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Tibicare

If you forget to take a tablet, take it as soon as you remember, unless more than 12 hours have passed since you were supposed to take it. If more than 12 hours have passed, do not take that dose. Do not take a double dose to make up for forgotten doses.

If you need to have surgery

If you are going to have surgery, inform your doctor that you are taking Tibicare. You should stop taking Tibicare 4 to 6 weeks before surgery to reduce the risk of blood clots (see Section 2, Blood clots in a vein). Consult your doctor when you can start taking Tibicare again.

If you stop taking Tibicare

Do not stop taking tibolone without consulting your doctor first, even if you feel better. It is important to take the medication for as long as your doctor told you. Otherwise, the signs or symptoms of estrogen deficiency may reappear.

If you have any other questions about the use of this product, ask your doctor or pharmacist.

4. Possible side effects

The following side effects are more frequently observed in women taking HRT compared to those who do not:

• breast cancer;
• abnormal growth of the layer that lines the uterus (endometrial hyperplasia or cancer);
• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolism);
• heart disease;
• stroke;
• possible memory loss if HRT is started after age 65.

For more information on these side effects, see section 2.

Like all medications, this medication can have side effects, although not all people experience them. Most of these effects are mild.

If you think you may have a serious side effect, consult your doctor immediately.

You may need to stop taking Tibicare:

• If you have high blood pressure
• If your skin or eyes turn yellow (jaundice)
• If you have a sudden, severe headache (see Section 2)
• If you have signs of a blood clot (see Section 2)
• If you have any of the situations listed in Section 2 (Do not take Tibicare)

Other side effects

Frequent(affect 1 in 10 women):

• Breast pain
• Stomach or pelvic pain
• Abnormal hair growth
• Vaginal bleeding or spotting

This is normal in the first two months of receiving HRT. If the bleeding continues, or if it starts some time after starting HRT, see section 2 "Irregular bleeding"

• Vaginal discomfort such as discharge, itching, and irritation
• Inflammation of the vulva and vagina (vulvovaginitis)
• Candidiasis
• Thickening of the layer that lines the uterus or cervix
• Tissue changes in the cervix
• Abnormal cervical discharge
• Weight gain

Uncommon(affect 1 in 100 women):

• Inflammation of hands, ankles, or feet - sign of fluid retention
• Stomach upset
• Acne
• Breast tenderness or pain
• Vaginal infections (thrush)
• Fungal infection

Rare(affect 1 in 1,000 women):

• Skin itching

Some women taking tibolone have also reported:

• Depression, dizziness, headache
• Joint and muscle pain
• Skin irritation or itching
• Loss of vision or blurred vision
• Changes in liver function laboratory tests

There have been reports of breast cancer and an increase in the growth of endometrial cells or endometrial cancer in women treated with tibolone.

Tell your doctor if any of the above symptoms are bothersome or persistent.

With other HRTs, the following adverse reactions have been reported:

• Gallbladder disease
• Skin disorders:
• Skin discoloration, especially on the face or neck, known as "pregnancy spots" (chloasma)
• Painful red nodules on the skin (erythema nodosum)
• Rash with redness or ulcers (erythema multiforme)

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that is not listed in this leaflet. You can also report them directly through the Spanish Medicines Monitoring System: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Tibicare 2.5 mg EFG tablets

Keep this medication out of sight and reach of children.

This medication does not require special storage conditions.

Store in the original packaging to protect it from light and moisture.

Do not use this medication after the expiration date shown on the blister pack and carton after CAD. The expiration date is the last day of the month indicated.

Medications should not be thrown away in drains or trash. Deposit the packaging and medications you no longer need at the SIGRE collection point in the pharmacy. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Package contents and additional information

Tibicare composition

• The active ingredient is tibolone.
• The other ingredients are lactose monohydrate (see section 4, "Tibicare contains lactose"), mannitol, potato starch, ascorbyl palmitate, and magnesium stearate.

Product appearance and package contents

Tibicare are white or off-white, round tablets, 6 mm in diameter, with a beveled edge and no markings.

They are available in packs of 1, 3, or 6 blisters containing 28 or 30 tablets.

Only some pack sizes may be marketed.

Marketing authorization holder

Procare Health Iberia, S.L.

Avda. Miguel Hernandez 21, Bajo

46450 Benifaió (Valencia)

Spain

Manufacturer

Cenexi

17, rue de Pontoise

95520 OSNY

FRANCE

This medication is authorized in the member states of the European Economic Area under the following names:

Country - Medication name

Germany: Tibelia 2.5 mg tablets

Belgium: Tibelia 2.5 mg tablets

Spain: Tibicare 2.5 mg EFG tablets

France: Tibolone CCD 2.5 tablets

Netherlands: Tibolon Mithra 2.5 mg tablets

Luxembourg: Tibelia 2.5 mg tablets

United Kingdom: Tibelia 2.5 mg tablets

Date of the last revision of this leaflet: September 2020

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)