Package Insert: Information for the Patient

Tibocina 2.5 mg Tablets EFG

Tibolone

Read this package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

1. What is Tibocina and how is it used

2. What you need to know before starting to take Tibocina

3. How to take Tibocina

4. Possible adverse effects

5. Storage of Tibocina

6. Contents of the package and additional informationl

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

Tibocina is a Hormone Replacement Therapy (HRT).

Tibocina is used in postmenopausal women who have not had a natural menstrual period for at least 12 months.

Tibocina is used for:

Relief of symptoms that occur after menopause.

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

Medical History and Regular Medical Check-Ups

The use of Hormone Replacement Therapy (HRT) or Tibolona involves certain risks that should be taken into account when deciding whether to start or continue treatment.

The experience in treating women with premature menopause (due to ovarian problems or surgery) is limited. If you have premature menopause, the risks of using HRT or Tibolona may be different. Please consult your doctor.

Before Starting (or Restarting) HRT or Tibocina

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

• Inform your doctor if you have any medical condition or 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 apply to you. If you are unsure about the conditions described below, consult your doctor before starting to take this medication.

-If you have or have had breast cancer or if you suspect you may have it,

-If you have a cancer that is sensitive to estrogen, such as endometrial cancer, or if you suspect you may have it,

-If you have vaginal bleeding of unknown cause,

-If you have excessive growth of the tissue that lines 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 bleeding disorder (such as protein C deficiency, protein S deficiency or antithrombin deficiency),

-If you have or have had any disease that causes blood clots in the arteries, such as myocardial infarction, stroke or angina pectoris,

-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 disorder called "porphyria" that is inherited,

-If you are allergic (hypersensitive) to tibolona or to any of the other components of this medication(including in section 6),

-If you are pregnant or think you may be pregnant,

-If you are breastfeeding.

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

If you have recently started menopause, do not start treatment with Tibocina until 12 months have passed since your last menstrual 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 these may worsen or recur during treatment with Tibocina. You should visit your doctor more frequently for check-ups:

-Fibrosis in your uterus,

-Abnormal growth of the tissue that lines the uterus (endometriosis) or a history of abnormal growth of the tissue that lines the uterus (endometrial hyperplasia),

-High risk of blood clots (see "Blood clots in a vein (thrombosis)"),

-High risk of developing a cancer that is dependent on estrogen (or you have had a mother, sister or grandmother who has had breast cancer),

-High blood pressure,

-Liver disease, such as a benign liver tumor,

-Diabetes,

-Galstones,

-Migraine or severe headaches,

-A disease of the immune system that affects several organs of the body (systemic lupus erythematosus (SLE)),

-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 Consult 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 may be symptoms of liver disease,
• Significant increase in blood pressure (symptoms may include headache, fatigue and dizziness),
• Migraines that are inexplicable and occur for the first time,
• If you become pregnant,
• If you experience symptoms of a possible blood clot such as:
• • Swelling and redness in the legs,
  • Sudden pain in the chest,
  • Difficulty breathing, for more information see the section "Blood clots in a vein (thrombosis)".

Note:Tibocina is not a contraceptive medication. If it has been less than 12 months since your last menstrual 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

Endometrial Hyperplasia and Endometrial Cancer

The results from clinical trials are inconsistent. One clinical trial identified a high risk of developing endometrial cancer in women who were not examined for endometrial abnormalities at the beginning 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 tibolona for 2.9 years, compared to no cases of endometrial cancer diagnosed in women treated with placebo (dummy treatment without active ingredient). This corresponds to a diagnosis of 0.8 additional cases of endometrial cancer per 1,000 women treated with tibolona for one year in the context of this study.

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

In patients using tibolona, the abnormal growth of the tissue that lines the uterus was measured using ultrasound.

Irregular Bleeding

You may experience irregular bleeding or spotting during the first3 to6 months of treatment with Tibocina. However, if the bleeding or spotting:

-Occurs for more than 6 months,

-Starts just after starting to take Tibocina for more than 6 months,

• Continues after stopping treatment,consult your doctor immediately.

Breast Cancer

The available data show that the use of tibolona increases the risk of breast cancer. The additional risk depends on the duration of use. 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 tibolona, but it cannot be ruled out that a similar pattern may occur.

Comparison

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

Check Your Breasts Regularly. Consult Your Doctor If You Notice Any Changes Such As:

• Formation of dimples in the skin,
• Changes in the nipple,
• Any lump that you can see or feel.

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

Ovarian Cancer

Ovarian cancer is rare, occurring less frequently than breast cancer. The use of HRT with estrogen-only or with combination of estrogen-progestogen has been associated with a slightly higher risk of ovarian cancer.

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

Blood Clots in a Vein (Thrombosis)

The risk of developing a blood clot in a vein is 1.3 to 3 times higher in patients on 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 developing a blood clot in a vein as you get older if you are affected by any of the following conditions. Inform your doctor if you experience any of the following situations:

• if you are pregnant or have recently given birth,
• if you are using estrogen,
• if you have not been able to walk for a long period of time due to major surgery, a wound or illness (see also section 3, "If you are to undergo surgery"),
• if you have a severe obesity index(BMI >30 kg/m2),
• if you have any bleeding disorder that requires long-term treatment to prevent blood clots,
• if any of your close relatives have or have had a blood clot in a vein, lung or other organ,
• if you have lupus erythematosus (LES),
• if you have cancer.

To distinguish the symptoms of a blood clot, see "Stop Taking Tibocina and Consult 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 old who are on HRT with estrogen-progestogen, it is slightly less likely to suffer a heart attack than those who are not on 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 stroke is 1.5 times higher in patients on HRT than in women who are not on treatment. The number of additional cases of stroke due to the use of HRT increases with the age of the patient.

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

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

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

Other Diseases

HRT does not prevent memory loss. Certain evidence shows a higher risk of memory loss in women who have started treatment with HRT after the age of 65. Consult your doctor for more information.

Other Medications and Tibocina

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

• Medications for blood clots (e.g., warfarin),
• Medications for epilepsy (e.g., phenobarbital, phenytoin and carbamazepine),
• Medications for HIV infections (e.g., nevirapine, efavirenz, ritonavir and nelfinavir),
• Medications for tuberculosis (such as rifampicin),
• Herbal remedies containing St. John's Wort (Hypericum perforatum),
• Midazolam(medication for insomnia),
• Tolbutamide (medication for diabetes)

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including those purchased without a prescription.

Clinical Trials

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

Pregnancy and Breastfeeding

Tibocina is indicated only for postmenopausal women. If you become pregnant, stop taking Tibocina and consult your doctor. Do not take Tibocina if you are breastfeeding.

Driving and Using Machines

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

Tibocina Contains Lactose

Patients with hereditary intolerance to galactose, total lactase deficiency or problems with glucose or galactose absorption should not take this medication.

Take Tibocina exactly as your doctor has told you to. 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 every day.

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

Do not take a preparation with progestagens together with Tibocina.

How to take Tibocina

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

What to consider when starting treatment with Tibocina

If your menopause occurs naturally, you should start taking Tibocina as soon as 1 year after your last natural menstrual period. If your ovaries have been surgically removed, 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 treating you before starting treatment with Tibocina to rule out any malignant disease.

If you want to switch from Tibocina to another medication containing estrogen and progestagen, please consult your doctor to know what to consider.

Before undergoing surgery

If you are 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 as to when you can start taking Tibocina again.

If you take more Tibocina than you should

It is unlikely that you will experience symptoms of overdose even if you take several tablets at the same time. In case of acute overdose, nausea, vomiting, and intermenstrual bleeding may occur. If necessary, consult your doctor to treat the symptoms.

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

If you forget to take Tibocina

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

Like all medications, Tibocina may cause side effects, although not everyone will experience them.Most of these side effects are mild.

The following diseases have been reported more frequently in users on THS treatment than in other women not on 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 old on THS treatment.

For more information about these diseases, see section 2.

Inform your doctor or pharmacist if you are concernedabout any possible side effect that you think may be caused by Tibocina treatment, see also section 2“Discontinue Tibocina treatment and consult your doctor immediately”.

Severe side effects, seek medical attention immediately

If you consider that you are experiencing symptoms of a severe side effect, seek medical attention immediately.

You may have to stop taking Tibocina:

• if your blood pressure increases,
• if your skin or the white of your eyes turn yellow (jaundice),
• if you experience unexplained migraines, type headache (see section 2 above),
• if you have symptoms of a blood clot (see section 2 above),
• if you have any of the problems listed 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 something to worry about in the first 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 covers the uterus,
• weight gain.

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

• acne,
• breast pain, or uncomfortable sensation in the breasts,
• vaginal infections.

Some women taking 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 discomfort,
• loss of vision or blurred vision,
• changes in liver function tests.

Cases of breast cancer or increased cell size or endometrial cancer have been reported in women on tibolone treatment.

• Inform 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 on treatment with other THS:

• biliary vesicular alterations
• skin alterations:

• skin discoloration, especially on the face or neck, known as "pregnancy spots" (melasma),
• red, 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 prospectus.You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information about the safety of this medication.

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

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

This medication does not require special storage conditions.

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

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. In this way, you will help protect the environment.

Composition of Tibocina

The active principle is tibolone.

Each tablet contains 2.5 mg of tibolone.

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

Appearance of the product and content of the container

Tibocina are white to off-white, flat and round tablets, approximately 6 mm in diameter.

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

Only some container sizes may be commercially marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Responsible for manufacturing

Aristo Pharma GmbHPharma 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

Last review date of this leaflet: November 2020

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