TIBOCINA 2.5 mg TABLETS

Introduction

Package Leaflet: Information for the Patient

Tibocina 2.5 mg tablets EFG

Tibolone

Read all of this leaflet carefully before you start 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, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Tibocina and what is it used for
2. What you need to know before you take Tibocina
3. How to take Tibocina
4. Possible side effects
5. Storage of Tibocina
6. Contents of the pack and other information

1. What is Tibocina and what is it used for

Tibocina 2.5 mg tablets. The active substance is: tibolone.

Tibocina is a Hormone Replacement Therapy (HRT).

Tibocina is used in postmenopausal women who have not had their natural periods for at least 12 months.

Tibocina is used for:

Relief of symptoms occurring after menopause.

During menopause, the amount of estrogen produced by the woman's body decreases. This can cause a feeling of heat in the face, neck, and chest ("hot flashes"). Tibocina relieves these symptoms after menopause. You will only be prescribed Tibocina if your symptoms are seriously affecting your daily activities.

2. What you need to know before you take Tibocina

Medical history and regular medical check-ups

The use of Hormone Replacement Therapy (HRT) or Tibolone involves certain risks that need to be considered when deciding whether to start treatment or continue with it.

Experience in treating women with premature menopause (due to an ovarian problem or surgical operation) is limited. If you have premature menopause, the risks of using HRT or tibolone may be different. Please consult your doctor.

Before starting (or restarting) HRT or Tibocina

Your doctor will ask you about your medical history or that of your family. Your doctor may decide to perform a medical examination. This may involve a breast examination or an internal examination if necessary.

• Tell your doctor if you have any illness or medical problem.

Regular medical check-ups

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

You should have regular mammograms, as recommended by your doctor.

Do not take Tibocina

If any of the following applies to you. If you are not sure about the conditions described below, consult your doctorbefore taking this medicine.

• if you have or have had breast cancer or if you suspect you may have it,
• if you have an estrogen-sensitive cancer, such as cancer of the lining of the uterus (endometrial cancer), or if it is suspected that you may have it,
• if you have vaginal bleeding of unknown cause,
• if you have excessive growth of the lining of the uterus (endometrial hyperplasia) that is not being treated,
• if you have or have had a blood clot in a vein (thrombosis), in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism),
• if you have or have had any problems with blood clotting (such as protein C, protein S, or antithrombin deficiency),
• if you have or have had any disease that causes blood clots in the arteries, such as a heart attack, stroke, or angina,
• if you have or have had any liver disease and your liver function tests have not returned to normal,
• if you have a rare blood problem called "porphyria" that is inherited,
• if you are allergic (hypersensitive) to tibolone or any of the other ingredients of this medicine (listed in section 6),
• if you are pregnant or think you may be pregnant,
• if you are breast-feeding.

If you experience any of the conditions mentioned above for the first time while taking Tibocina, stop treatment immediately and consult your doctor or pharmacist.

If you have just started menopause, do not start treatment with Tibocina until 12 months have passed since your last natural period. If you start treatment before this, you may experience irregular bleeding.

Warnings and precautions

Consult your doctor before taking Tibocina. 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 Tibocina. You should see your doctor more often for check-ups:

• fibroids in your uterus,
• abnormal growth of the lining of the uterus (endometriosis) or a history of abnormal growth of the lining of the uterus (endometrial hyperplasia),
• high risk of blood clots (see "Blood clots in a vein (thrombosis)"),
• high risk of estrogen-dependent cancer (or have had a mother, sister, or grandmother who has had breast cancer),
• high blood pressure,
• liver disease, such as a benign liver tumor,
• diabetes,
• gallstones,
• migraine or severe headaches,
• a disease of the immune system that affects many organs of the body (systemic lupus erythematosus),
• epilepsy,
• asthma,
• a disease that affects hearing (otosclerosis),
• very high levels of fat in the blood (triglycerides),
• fluid retention due to a heart or kidney problem.

Stop taking Tibocina and see your doctor immediately

If you are taking HRT or Tibocina and experience any of the following symptoms:

• any of the conditions mentioned in the section "Do not take Tibocina",
• yellowing of the skin and eyes (jaundice), as these can be symptoms of liver disease,
• a significant increase in blood pressure (symptoms may be headache, tiredness, and 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 the section "Blood clots in a vein (thrombosis)".

Note:Tibocina is not a contraceptive. If it has been less than 12 months since you had your last natural period or you are under 50 years of age, you may need to take additional contraceptive measures to prevent pregnancy. Consult your doctor for advice.

HRT and Cancer

Excessive growth of the lining of the uterus (endometrial hyperplasia) and cancer of the lining of the uterus (endometrial cancer).

The results from clinical trials are inconsistent. One clinical trial identified a high risk of endometrial cancer in women who had not been examined for endometrial abnormalities at the start of the study (LIFT Study, mean age 68 years). In this study, four cases of endometrial cancer were diagnosed in the group of patients treated with tibolone for 2.9 years, compared to no cases of endometrial cancer diagnosed in women treated with placebo (dummy treatment with no active ingredient). This corresponds to a diagnosis of 0.8 additional cases of endometrial cancer per 1,000 women treated with tibolone for one year in the context of this study.

Observational studies have consistently shown that patients treated with tibolone have an increased risk of being diagnosed with endometrial cancer. This risk increases with the duration of treatment.

In patients using tibolone, the growth of the lining of the uterus was measured by ultrasound.

Irregular bleeding

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

• lasts longer than the first 6 months,
• starts just after you have started taking Tibocina after more than 6 months,
  • continues after you have stopped treatment, consult your doctor immediately.

Breast cancer

Existing data show that the use of tibolone increases the risk of breast cancer. The additional risk depends on the time during which you use 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 on the persistence of risk after stopping tibolone, but a similar pattern cannot be ruled out.

Comparison

Women taking tibolone have a lower risk than women using combined HRT and a similar risk to women using estrogen-only HRT.

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

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

• Make an appointment with your doctor as soon as possible.

Ovarian cancer

Ovarian cancer is rare, it occurs less frequently than breast cancer. The use of HRT with estrogen alone or with a combination of estrogen-progestogen has been associated with a slightly increased risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women aged 50-54 who have not been treated with HRT, about 2 cases of ovarian cancer have been observed per 2,000 women over a 5-year period. In women who have taken HRT for 5 years, about 3 cases have been observed per 2,000 patients (i.e., about one additional case).

With the use of Tibocina, the risk of ovarian cancer is similar to other types of HRT.

Effects of HRT on the heart and blood 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 non-patients, especially during the first year of treatment.

Blood clots can be serious, and if one travels to the lungs, it can cause chest pain, shortness of breath, or even death.

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

• if you are pregnant or have recently had a baby,
• if you are using estrogens,
• if you have not been able to walk for a long time due to major surgery, injury, or illness (see also section 3, "If you are going to have surgery"),
• if you have a severe overweight index (BMI >30 kg/m2),
• if you have any blood clotting problems that require long-term treatment to prevent clots,
• if any of your close relatives have or have had a blood clot in a leg, lung, or other organ,
• if you have systemic lupus erythematosus (SLE),
• if you have cancer.

To distinguish the symptoms of a blood clot, see "Stop taking Tibocina and see your doctor immediately".

Heart disease (heart attack)

There is no evidence that the use of HRT or Tibocina prevents heart attacks. In women over 60 years of age who are taking combined estrogen-progestogen HRT, it is slightly less likely that they will have a heart attack than in those who have not been taking HRT.

For women who have had their uterus removed and are taking HRT with estrogen only for 5 years, there has been little or no increase in the risk of breast cancer.

Stroke

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

Recent studies suggest that HRT and tibolone increase the risk of stroke. This increased risk has been observed mainly in postmenopausal women over 60 years of age.

On average, it is expected that during a 5-year period, 3 out of 1,000 women aged 50 who do not take tibolone will have a stroke, while for women of this age who take tibolone, the figure may be 7 out of 1,000 (i.e., 4 more cases).

On average, it is expected that during a 5-year period, 11 out of 1,000 women aged 60 who do not take tibolone will have a stroke, while for women of this age who take tibolone, the figure may be 24 out of 1,000 (i.e., 13 more cases).

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.

Other medicines and Tibocina

Some medicines may interfere with the effect of Tibocina. This can cause irregular bleeding. This occurs with the following medicines:

• medicines to prevent blood clots (e.g., warfarin),
• medicines for epilepsy (e.g., phenobarbital, phenytoin, and carbamazepine),
• medicines for HIV infections (e.g., nevirapine, efavirenz, ritonavir, and nelfinavir),
• medicines for tuberculosis (such as rifampicin),
• herbal remedies containing St. John's Wort (Hypericum perforatum),
• midazolam(a medicine for insomnia),
• tolbutamide (a medicine for diabetes)

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

Clinical tests

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

Pregnancy and breast-feeding

Tibocina is indicated only for postmenopausal women. If you become pregnant, stop treatment with Tibocina and consult your doctor. Do not take Tibocina if you are breast-feeding.

Driving and using machines

There is no information to suggest that the use of Tibocina affects driving or the use of machines.

Tibocina contains lactose

Patients with hereditary galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

3. How to take Tibocina

Always take Tibocina exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist again.

How much Tibocina to take and for how long

Unless your doctor has prescribed a different dose, the usual dose is: one tablet a day, preferably at the same time each day.

Your doctor will try to prescribe 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.

Do not take a preparation with progestogens along with Tibocina.

How to take Tibocina

You should take your tablets with a little water or another drink, preferably at the same time each day.

What to consider when starting treatment with Tibocina

If in your case menopause occurs naturally, you should start taking Tibocina as soon as 1 year after your last menstrual period. If you have had your ovaries removed by surgery, you can start taking Tibocina immediately.

If you want to start taking Tibocina and have experienced irregular or unexpected vaginal bleeding, please make sure to contact the doctor who is treating you before starting treatment with Tibocina to rule out any malignant disease.

If you want to switch from Tibocina to another medicine that contains an estrogen and a progestogen, please consult your doctor to find out what you should consider.

If you are going to have surgery

If you are going to undergo a surgical procedure, inform your surgeon that you are taking Tibocina. You may need to stop taking Tibocina approximately 4 to 6 weeks before the operation to reduce the risk of a blood clot (see section 2 "Blood clots in a vein (thrombosis)"). Consult your doctor when you can take Tibocina again.

If you take more Tibocina than you should

It is unlikely that symptoms of intoxication will occur even if several tablets are taken at the same time. In case of acute overdose, nausea, vomiting, and intermenstrual bleeding may occur. If necessary, consult your doctor so that they can treat the symptoms.

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 medicine and the amount taken.

If you forget to take Tibocina

If you forget to take your tablet at the usual time, take your missed tablet as soon as possible unless more than 12 hours have passed since the last intake. In this case, do not take the missed tablet and take the next tablet at the usual time.

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

4. Possible side effects

Like all medicines, Tibocina can cause side effects, although not everyone gets them. Most of these side effects are mild.

The following diseases have been reported more frequently in users undergoing THS treatment than in women who are not undergoing treatment:

• breast cancer,
• abnormal growth of the layer that covers the uterus (endometrial hyperplasia or endometrial cancer),
• ovarian cancer,
• blood clots in the legs or lungs (venous thromboembolism),
• heart disease,
• stroke,
• probable memory loss in women over 65 years of age undergoing THS treatment.

For more information about these diseases, see section 2.

Tell your doctor or pharmacist if you are concernedabout any possible side effect that you think is caused by treatment with Tibocina, see also section 2 "Stop treatment with Tibocina and consult your doctor immediately".

Severe side effects, go to your doctor immediately

If you think you are experiencing symptoms of a severe side effect, go to your doctor immediately.

You will likely need to stop taking Tibocina:

• if your blood pressure increases,
• if your skin or the whites of your eyes turn yellow (jaundice),
• if you experience unexplained migraines, headache type (see section 2 above),
• if you have symptoms of a blood clot (see section 2 above),
• if you have any of the problems that appear in section 2, do not take Tibocina.

Other side effects

Frequent(may affect up to 1 in 10 women):

• breast pain,
• stomach or pelvic pain,
• unusual hair growth,
• vaginal bleeding or spotting,

This is not a concern in the first few months of starting THS treatment. If bleeding continues or starts after a while of being on THS treatment, see section 2.

• vaginal problems such as increased secretions, itching, irritation, and candidiasis,
• growth of the layer that lines the uterus,
• weight gain.

Uncommon(may affect up to 1 in 100 women):

• acne,
• nipple pain or discomfort in the breasts,
• vaginal infections.

Some women who take tibolone have also reported:

• depression, dizziness, headache, migraine,
• muscle or joint pain,
• skin problems such as erythema or itching,
• swelling of the hands, feet, and ankles, sign of fluid retention,
• stomach upset,
• vision loss or blurred vision,
• changes in liver tests.

Cases of breast cancer or increased cell size or cancer of the layer that covers the uterus have been reported in women undergoing tibolone treatment.

• Tell your doctor or pharmacist if any of the side effects continue or become a problem.

The following side effects have been reported by other patients undergoing treatment with other THS:

• bile duct disorders
• skin disorders:

• skin discoloration, especially on the face or neck, called "pregnancy spots" (chloasma),
• red and painful skin nodules (erythema nodosum),
• skin eruptions with red bumps and eczema (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 does not appear in this leaflet. You can also report them directly through the Spanish Medicines Pharmacovigilance System: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Tibocina

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging after "EXP". The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Do not use this medicine if you notice that the blister is damaged or even if it is not, or if the packaging appears to be intact.

Medicines should not be thrown down the drain or into the trash. Deposit the packaging and medicines you no longer need at the SIGRE point in the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Tibocina

The active ingredient is tibolone.

Each tablet contains 2.5 mg of tibolone.

The other ingredients are: potato starch, lactose monohydrate, magnesium stearate (vegetable origin), and ascorbyl palmitate.

Appearance of the product and package contents

Tibocina is a white to off-white, flat, and round tablet, approximately 6 mm in diameter.

Tibocina is available in packs of 1x28, 3x28, and 6x28 tablets.

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Manufacturer

Aristo Pharma GmbH

Wallenroder Str. 8-10

13435 Berlin

Germany

or

Salutas Pharma GmbH

Otto Von Guericke Alle, 1

Barleben D-39179

Germany

or

Lindopharm GmbH

Neustrasse 82,

D-40721 Hilden,

Germany

This medicine is authorized in the Member States of the European Economic Area under the following names:

Belgium:Tibocina 2.5 mg tablets

Spain:Tibocina 2.5 mg tablets EFG

Netherlands:Tibocina 2.5 mg tablets

Date of the last revision of this leaflet: November 2020

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