Tibocina 2.5 mg tablets EFG

Package Leaflet: Information for the User

Introduction

Package Leaflet: Information for the Patient

Tibocina 2.5 mg Tablets EFG

Tibolone

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

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

Leaflet Contents

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

1. What Tibocina is and what it is 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 natural menstruation for at least 12 months.

Tibocina is used for:

Relief of symptoms occurring after menopause.

During menopause, the amount of estrogens produced by a woman's body decreases. This may cause a sensation of heat in the face, neck, and chest ("hot flushes"). Tibocina relieves these postmenopausal symptoms. Tibocina will be prescribed to you only if your symptoms seriously interfere with your daily activities.

2. What you need to know before starting Tibocina

Medical history and periodic medical check-ups

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

Experience in treating women with premature menopause (due to ovarian problems or surgical removal of ovaries) is limited. If you have premature menopause, the risks of using HRT or tibolone may differ. Please consult your doctor.

Before starting (or restarting) HRT or Tibocina

Your doctor will ask about your personal and family medical history. Your doctor may decide to perform a prior medical examination, which may include a breast examination or internal pelvic exam, if necessary.

• Inform your doctor if you have any medical condition or health problem.

Periodic medical check-ups

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

Regular mammograms should be performed as recommended by your doctor.

Do not take Tibocina

If any of the following apply to you. If you are unsure about any of the conditions listed below, consult your doctor before starting this medicine.

• if you have or have ever had breast cancer, or suspect you may have it,
• if you have an estrogen-sensitive cancer, such as cancer of the lining of the womb (endometrial cancer), or if it is suspected,
• if you have vaginal bleeding of unknown cause,
• if you have excessive growth of the lining of the womb (endometrial hyperplasia) that is not being treated,
• if you have or have ever 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 ever had blood clotting disorders (such as protein C deficiency, protein S deficiency, or antithrombin deficiency),
• if you have or have ever had a disease causing blood clots in arteries, such as heart attack, stroke, or angina,
• if you have or have ever had liver disease and liver function tests have not returned to normal,
• if you have a rare inherited blood disorder called "porphyria",
• if you are allergic (hypersensitive) to tibolone or to 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 breastfeeding.

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

If you have just entered menopause, do not start treatment with Tibocina until 12 months have passed since your last natural menstrual period. Starting treatment earlier may result in irregular bleeding.

Warnings and precautions

Talk to your doctor before taking Tibocina. Consult your doctor if you have or have had any of the following conditions before starting treatment, as they may recur or worsen during treatment with Tibocina. In such cases, you may need more frequent medical check-ups:

• fibroids in the uterus,
• abnormal growth of the lining of the uterus (endometriosis) or history of abnormal growth of the uterine lining (endometrial hyperplasia),
• increased risk of blood clots (see “Blood clots in a vein (thrombosis)”),
• increased risk of estrogen-dependent cancer (or if you have a mother, sister, or grandmother who has had breast cancer),
• high blood pressure,
• liver disease, such as benign liver tumor,
• diabetes,
• gallstones,
• migraine or severe headaches,
• an immune system disease affecting multiple organs (systemic lupus erythematosus, SLE),
• epilepsy,
• asthma,
• a hearing disorder (otosclerosis),
• very high levels of fat in the blood (triglycerides),
• fluid retention due to heart or kidney problems.

Stop taking Tibocina and contact your doctor immediately

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

• any of the conditions listed in the section “Do not take Tibocina”,
• yellowing of the skin or eyes (jaundice), as these may be signs of liver disease,
• a significant increase in blood pressure (symptoms may include headache, fatigue, and dizziness),
• new onset of severe, unexplained headaches resembling migraines,
• 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 section “Blood clots in a vein (thrombosis)”.

Note: Tibocina is not a contraceptive. If less than 12 months have passed since your last natural menstrual period or if you are under 50 years of age, you may need to use 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)

Clinical trial results are inconsistent. One clinical trial identified an increased risk of 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 tibolone treatment group over 2.9 years, compared to no cases in women receiving placebo (inactive treatment). This corresponds to 0.8 additional cases of endometrial cancer per 1,000 women treated with tibolone per year in the context of this study.

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

Abnormal growth of the lining of the uterus has been measured in patients using tibolone via ultrasound monitoring.

Irregular bleeding

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

• continues beyond the first 6 months,
• starts after you have been taking Tibocina for more than 6 months,
  • continues after stopping treatment, contact your doctor immediately.

Breast cancer

Available data show that the use of tibolone increases the risk of breast cancer. The additional risk depends on how long you take tibolone. In HRT studies, after stopping HRT, the additional risk decreased over time, but the risk may persist for 10 years or more in women who used HRT for more than 5 years. Data on risk persistence after stopping tibolone are not available, but a similar pattern cannot be ruled out.

Comparison

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

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

• dimpling of the skin,

• changes in the nipple,

• any lump you can see or feel.

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

Ovarian cancer

Ovarian cancer is rare and occurs less frequently 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 varies with age. For example, in women aged 50 to 54 years not using HRT, about 2 cases of ovarian cancer occur per 2,000 women over a 5-year period. In women who have taken HRT for 5 years, about 3 cases per 2,000 women are 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 blood 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 women taking HRT than in those not taking HRT, 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.

Your risk of developing a blood clot in the veins increases with age and if you have any of the following conditions. Inform your doctor if you experience any of the following:

• if you are pregnant or have recently given birth,
• if you are using estrogens,
• if you have been unable to walk for a prolonged period due to major surgery, injury, or illness (see also section 3, “If you are going to have surgery”),
• if you have severe obesity (BMI >30 kg/m²),
• if you have a blood clotting disorder requiring long-term treatment to prevent clots,
• if any of your close relatives have or have ever had a blood clot in the leg, lung, or other organ,
• if you have systemic lupus erythematosus (SLE),
• if you have cancer.

For symptoms of a blood clot, see “Stop taking Tibocina and contact your doctor immediately”.

Heart disease (heart attack)

There is no evidence that HRT or Tibocina prevents heart attacks. In women over 60 years of age using estrogen-progestagen HRT, the likelihood of a heart attack is slightly lower than in women not using HRT.

For women who have had a hysterectomy and are using estrogen-only HRT for 5 years, little or no increased risk of breast cancer has been observed.

Stroke

The risk of stroke is 1.5 times higher in women taking HRT than in women not taking HRT. The number of additional stroke cases due to HRT use increases with the woman's age.

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

On average, over a 5-year period, 3 out of 1,000 women aged 50 who do not take tibolone are expected to have a stroke, while the figure for women of this age taking tibolone may be 7 out of 1,000 (i.e., 4 additional cases).

On average, over a 5-year period, 11 out of 1,000 women aged 60 who do not take tibolone are expected to have a stroke, while the figure for women of this age taking tibolone may be 24 out of 1,000 (i.e., 13 additional cases).

Other diseases

HRT does not prevent memory loss. Some evidence suggests an increased risk of memory loss in women who start HRT after age 65. Consult your doctor for further information.

Other medicines and Tibocina

Some medicines may interfere with the effect of Tibocina, which may cause irregular bleeding. These include:

• medicines for blood clots (e.g., warfarin),
• medicines for epilepsy (e.g., phenobarbital, phenytoin, and carbamazepine),
• medicines for HIV infection (e.g., nevirapine, efavirenz, ritonavir, and nelfinavir),
• medicines for tuberculosis (e.g., 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 need to take any other medicines, including those obtained without a prescription.

Laboratory tests

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

Pregnancy and breastfeeding

Tibocina is intended 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 indicating that the use of Tibocina affects driving or operating machinery.

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 instructed you. If in doubt, consult your doctor or pharmacist again.

How much Tibocina should you take and for how long

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

Your doctor will aim to prescribe the lowest effective 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 progestogen-containing preparation together with Tibocina.

How to take Tibocina

You should take your tablets with a glass of water or other drink, preferably at the same time each day.

What to consider when starting treatment with Tibocina

If your menopause occurred naturally, you should start taking Tibocina no earlier than 1 year after the last menstrual period. If your ovaries have been surgically removed, you may start taking Tibocina immediately.

If you wish to start taking Tibocina and have experienced irregular or unexpected vaginal bleeding, please contact your treating doctor before starting Tibocina treatment to rule out any malignant disease.

If you wish to switch from Tibocina to another medication containing an oestrogen and a progestogen, please consult your doctor for advice on what you should consider.

If you are going to have surgery

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

If you take more Tibocina than you should

It is unlikely that symptoms of poisoning 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 for symptomatic treatment.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number: 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 missed tablet as soon as possible, unless more than 12 hours have passed since the usual time. In this case, do not take the missed tablet and take the next tablet at the usual time.

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

4. Possible adverse effects

Like all medicines, Tibocina may produce adverse effects, although not everyone experiences them. Most of these adverse effects are mild in nature.

The following conditions have been reported more frequently in women receiving hormone replacement therapy (HRT) than in women not receiving such treatment:

• breast cancer,
• abnormal growth of the lining of the uterus (endometrial hyperplasia or endometrial cancer),
• ovarian cancer,
• blood clots in the legs or lungs (venous thromboembolism),
• heart disease,
• stroke,
• possible memory loss in women over 65 years of age receiving HRT.

For further information about these conditions, see section 2.

Tell your doctor or pharmacist if you are concerned about any possible adverse effect you think may be due to treatment with Tibocina. See also section 2: “Stop taking Tibocina and contact your doctor immediately.”

Serious adverse effects – see your doctor immediately

If you think you are experiencing symptoms of a serious adverse effect, contact your doctor immediately.

You may 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 migraine-type headaches (see section 2 above),
• if you have symptoms of a blood clot (see section 2 above),
• if you develop any of the conditions listed in section 2. Do not take Tibocina.

Other adverse 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 cause for concern during the first few months of starting HRT. However, if bleeding continues or starts after a period of time on HRT, see section 2.

• vaginal problems such as increased discharge, itching, irritation, and candidiasis,
• thickening of the uterine lining,
• weight gain.

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

• acne,
• nipple pain or discomfort 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, a sign of fluid retention,
• stomach discomfort,
• loss of vision or blurred vision,
• changes in liver function tests.

Cases of breast cancer or increased size of cells or cancer of the uterine lining have been reported in women taking tibolone.

• Inform your doctor or pharmacist if any of these adverse effects persist or become troublesome.

The following adverse effects have been reported by other patients receiving other HRTs:

• gallbladder disorders,

• skin disorders:

• skin discoloration, especially on the face or neck, known as “pregnancy mask” (chloasma),

• red, painful skin nodules (erythema nodosum),

• skin rashes with red bumps and eczema (erythema multiforme).

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse 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 expiry date stated on the packaging after "EXP". The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

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

Medicines must not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at the SIGRE Point located at your pharmacy. If in doubt, ask your pharmacist how to dispose of unused medicines and their packaging. This way, you will help protect the environment.

6. Contents of the pack and other information

Composition of Tibocina

The active substance is tibolone.

Each tablet contains 2.5 mg of tibolone.

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

Appearance of the product and contents of the container

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

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

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Sandoz Farmacéutica, S.A.

Parque Norte Business Centre

Roble Building

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 medicinal product 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 most recent review of this leaflet: November 2020

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