Tibocina

Patient Information Leaflet

TIBOCINA 2.5 mg tablets

Tibolone
Equivalent medicine
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. 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. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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 side 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
The active substance is: tibolone.
Tibocina is a hormone replacement therapy (HRT). It contains the active substance tibolone, which has beneficial effects on various organ tissues in the body such as bones, brain, and vagina. Tibocina is used in postmenopausal women who have not had their natural menstrual period for the past 12 months.
Tibocina is used for the following indications:

Relief of symptoms occurring after menopause
During menopause, the amount of oestrogens produced by a woman's body decreases. This may cause undesirable symptoms such as a feeling of warmth in the face, neck, and chest ("hot flushes"). Tibocina relieves these postmenopausal symptoms. This medicine will be prescribed to you only if your symptoms severely affect your daily life.

Prevention of osteoporosis
After menopause, some women may develop brittle bones (osteoporosis). Discuss all available treatment options with your doctor.
If your doctor has told you that you have a high risk of fractures due to a medical condition called osteoporosis and other medicines are not suitable for you, you may start using Tibocina to prevent osteoporosis after menopause.

There are three types of hormone replacement therapy:

• Oestrogen-only HRT
• Combined HRT, which contains two types of female hormones, known as oestrogen and progestogen.
• Tibocina, which contains the active substance called tibolone.

Tibolone works differently from other types of hormone replacement therapies, as this medicine contains the active substance tibolone instead of female hormones (i.e. oestrogens and progestogens). The body metabolises tibolone to produce natural hormones. Its beneficial effects are similar to those of combined HRT.

2. What you should know before taking Tibocina

For information on when you can start taking Tibocina (including after hysterectomy, a surgical procedure to remove the uterus), see section 3.
Medical history and regular check-ups
Hormone replacement therapy or treatment with Tibocina involves certain risks that must be considered when deciding whether to start or continue taking this medicine. This is particularly important if you are over 60 years of age.
Experience in treating women who have entered premature menopause (due to ovarian failure or surgery) is limited. If you have entered premature menopause, the risks associated with hormone replacement therapy or use of Tibocina may differ. Consult your doctor.
Before starting (or restarting) hormone replacement therapy or taking Tibocina
Your doctor will discuss your medical problems and family medical history with you. Your doctor may also decide to perform a physical examination. This may include a breast examination and/or an internal examination, if necessary.
→ Inform your doctor if you suffer from any medical conditions or diseases.
Regular check-ups
Once you have started treatment with Tibocina, you must visit your doctor for regular check-ups (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing treatment with Tibocina.
Have regular mammographic screening as recommended by your doctor.
Make sure you:

• have regular breast screening and Pap tests
• regularly check your breasts for any changes, such as skin dimpling, changes in the nipple, or lumps that can be seen or felt

Do not take Tibocina:
If any of the conditions listed below apply to you, do not take this medicine. If you have any doubts about any of the points listed below, consult your doctor before taking this medicine. Do not take this medicine:

• If you have or have previously had breast cancer, or if you suspect you may have it
• If you suffer from an estrogen-sensitive tumour, such as cancer of the lining of the uterus (endometrium), or if you suspect you may have it
• If you have unexplained vaginal bleeding
• If you have untreated excessive thickening of the uterine lining (endometrial hyperplasia)
• If you have or have previously had a blood clot in a vein (thrombosis), for example in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism)
• If you suffer from a blood clotting disorder (such as protein C, protein S or antithrombin deficiency)
• If you suffer from or have recently suffered from an arterial disease caused by blood clots, such as heart attack, stroke or angina
• If you suffer from liver disease and liver function test results have not returned to normal
• If you suffer from a rare inherited blood disorder called "porphyria"
• If you are allergic 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 any of the above conditions occur for the first time while you are taking Tibocina, stop taking the medicine immediately and consult your doctor without delay.
If you have just entered menopause, do not take Tibocina until 12 months have passed since your last natural period. If you start taking the medicine before this time, you may experience irregular bleeding.
Warnings and precautions
Talk to your doctor before taking Tibocina. Inform your doctor if you have ever suffered from any of the following conditions, as they may reappear or worsen during treatment with Tibocina. In such cases, your doctor may need to perform check-ups more frequently:

• uterine fibroids
• growth of the inner lining of the uterus outside the uterus (endometriosis), or history of excessive growth of the uterine lining (endometrial hyperplasia)
• increased risk of developing blood clots (see "Blood clots in a vein [thrombosis]")
• increased risk of developing an oestrogen-sensitive tumour (e.g. if your mother, sister or grandmother had breast cancer)
• high blood pressure
• liver disease, such as benign liver tumour
• diabetes
• gallstones
• migraine or severe headaches
• an autoimmune disease affecting multiple organs (systemic lupus erythematosus, SLE)
• epilepsy
• asthma
• a disease affecting the eardrum and hearing (otosclerosis)
• very high levels of fats (triglycerides) in the blood
• fluid retention due to heart or kidney problems

For athletes: using this medicine without therapeutic need constitutes doping and may lead to a positive anti-doping test.
Stop taking Tibocina and consult your doctor immediately if, during hormone replacement therapy or while taking Tibocina, you notice any of the following:

• any of the conditions listed under "Do not take Tibocina"
• yellowing of the skin or whites of the eyes (jaundice). These may be signs of liver disease
• a marked increase in blood pressure (symptoms may include headache, fatigue, dizziness)
• new-onset migraine-like headaches
• if you become pregnant
• if you notice signs of a blood clot, such as:
• painful swelling and redness in the legs
• sudden chest pain
• difficulty breathing For further information, see "Blood clots in a vein (thrombosis)".

Note: Tibocina is not a contraceptive. If less than 12 months have passed since your last menstrual period or if you are under 50 years of age, you may still need to use an additional contraceptive method to prevent pregnancy. Ask your doctor for advice.
Hormone replacement therapy and cancer
Excessive thickening of the uterine lining (endometrial hyperplasia) and cancer of the lining of the uterus (endometrial carcinoma)
Among women using tibolone, there have been reports of increased cell growth or cancer of the uterine lining. The risk of cancer of the uterine lining increases the longer the medicine is taken.
Irregular bleeding
During the first 3–6 months of treatment with Tibocina, you may experience irregular bleeding or spotting. Consult your doctor as soon as possible if bleeding or spotting:

• persists beyond the first 6 months
• starts after you have been taking Tibocina for more than 6 months
• continues after you have stopped taking Tibocina → see your doctor as soon as possible.

Breast cancer
Evidence suggests that combined oestrogen-progestin therapy, and possibly also oestrogen-only hormone replacement therapy, increases the risk of breast cancer. The additional risk depends on how long hormone replacement therapy has been taken. The additional risk becomes evident within a few years. However, within a few years (at most 5) after stopping treatment, the risk returns to normal.
Comparison
Women taking tibolone have a lower risk compared to women on combined hormone replacement therapy and a similar risk to those on oestrogen-only hormone replacement therapy.
Check your breasts regularly. Consult your doctor as soon as possible if you notice any changes, such as:

• skin dimpling or indentations
• nipple changes
• any lumps visible or palpable → make an appointment with your doctor as soon as possible.

Ovarian cancer
Ovarian cancer is rare – much rarer than breast cancer. The use of oestrogen-only or combined oestrogen-progestin HRT has been associated with a slight increase in the risk of ovarian cancer. The risk of ovarian cancer varies with age. For example, among women aged 50 to 54 years not using HRT, about 2 in 21,000 will be diagnosed with ovarian cancer over a 5-year period. Among women using HRT for 5 years, there will be about 3 cases in 2,000 women treated (i.e. about 1 additional case).
With the use of Tibocina, the increase in risk of ovarian cancer is similar to other types of hormone replacement therapy.
Effects of hormone replacement therapy on the heart and circulation
Blood clots in a vein (thrombosis)
The risk of blood clots in veins is approximately 1.3 to 3 times higher in women taking hormone replacement therapy compared to women not taking it, especially during the first year of treatment.
Blood clots can be serious, and if they travel to the lungs, they can cause chest pain, shortness of breath, fainting or even death.
Your likelihood of developing a blood clot in a vein increases with age and in the following situations. If any of these apply to you, inform your doctor:

• if you are pregnant or have recently given birth
• if you are taking oestrogens
• if you cannot walk for long periods due to major surgery, trauma or illness (see also section 3, "In case of surgery")
• if you are severely overweight (BMI >30 kg/m²)
• if you suffer from a blood clotting disorder requiring long-term anticoagulant treatment
• if any of your close relatives have ever had blood clots in the legs, lungs or other organs
• if you suffer from systemic lupus erythematosus (SLE)
• if you have a tumour. For signs of a blood clot, see the section "Stop taking Tibocina and consult your doctor immediately".

Comparison
Among women aged 50 to 60 not taking hormone replacement therapy, it is expected that on average, between 4 and 7 out of 1,000 will develop a blood clot in a vein over a 5-year period.
Among women aged 50 to 60 taking combined oestrogen-progestin hormone replacement therapy for more than 5 years, the number will be between 9 and 12 out of 1,000 (i.e. 5 additional cases).
With the use of Tibocina, the increase in the risk of developing a blood clot in a vein is lower than with other types of hormone replacement therapy.
Heart disease (heart attack)
There is no evidence that hormone replacement therapy or tibolone prevent heart attacks.
Women over 60 years of age taking combined oestrogen-progestin hormone replacement therapy have a slightly higher chance of developing heart disease compared to those not taking hormone replacement therapy.
Although the risk of heart disease strongly depends on age, the number of additional cases of heart disease due to the use of oestrogen-progestin HRT is very low in healthy women close to menopause, but increases with age.
There is no evidence suggesting that the risk of myocardial infarction with Tibocina differs from that with other HRTs.
Stroke
Recent research suggests that HRT and tibolone slightly increase the risk of stroke.
The increased risk has been observed mainly in women over 60 years of age.
Other factors that can increase the risk of stroke include:

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

If you are concerned about any of these factors, consult your doctor to determine whether you should take HRT.
Comparison
Among women aged 50 to 60 not taking tibolone, it is expected that on average, 3 out of 1,000 will suffer a stroke over a 5-year period. Among women aged 50 to 60 taking tibolone, this figure rises to 7 out of 1,000 (i.e. 4 additional cases).
Among women aged 60 to 70 not taking tibolone, it is expected that on average, 11 out of 1,000 will have a stroke over a 5-year period.
Among women aged 60 to 70 taking tibolone, this figure rises to 24 out of 1,000 (i.e. 13 additional cases).
Other conditions and Tibocina
Hormone replacement therapy does not prevent memory loss. There is some evidence of a higher risk of memory loss in women who start hormone replacement therapy after age 65. Consult your doctor.
Tibocina is not indicated for contraceptive purposes.
Treatment with Tibocina causes a marked dose-dependent reduction in HDL cholesterol (from -16.7% with a 1.25 mg dose to -21.8% with the 2.5 mg dose after 2 years).
Triglyceride and lipoprotein (a) levels were also reduced. The reduction in total cholesterol and VLDL-C levels was not dose-dependent. LDL-C levels remained unchanged. The clinical significance of these findings is not yet known.
Oestrogens can cause fluid retention; therefore, patients with cardiac or renal dysfunction should be closely monitored.
Women with pre-existing hypertriglyceridaemia should be carefully monitored during oestrogen replacement or hormone replacement therapy, as rare cases of significant increases in plasma triglycerides and subsequent pancreatitis have been reported with oestrogen therapy.
Treatment with Tibocina causes a much smaller reduction in levels of thyroxine-binding globulin (TBG) and total T4. Total T3 levels remain unchanged. Tibocina decreases levels of sex hormone-binding globulin (SHBG), while levels of corticosteroid-binding globulin (CBG) and circulating cortisol remain unchanged.
Other medicines and Tibocina
Inform your doctor or pharmacist if you are taking or have recently taken any other medicines.
Some medicines may interfere with the effect of Tibocina. This could cause irregular bleeding. This applies to the following medicines:

• medicines for blood clotting (such as warfarin)
• medicines for epilepsy (such as phenobarbital, phenytoin and carbamazepine)
• medicines for HIV infection (such as 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)

Laboratory tests
If you need to have a blood test, inform your doctor or healthcare professional that you are taking Tibocina, as this medicine may affect the results of certain tests.
Surgery
If you are scheduled for surgery, make sure to inform your doctor. You may need to stop taking HRT approximately 4–6 weeks before the procedure to reduce the risk of a blood clot. Your doctor will advise you when you can resume HRT.
Tibocina with food and drink
You may eat and drink normally while taking Tibocina.
Pregnancy and breastfeeding
Tibocina is intended for use in postmenopausal women only. If you become pregnant, stop taking Tibocina and consult your doctor.
Do not take Tibocina if you are pregnant, think you may be pregnant, or are breastfeeding.
Driving and using machines
Tibocina has no known effect on the ability to drive or use machines.
Tibocina contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, consult him before taking this medicine.
If you are concerned about any of the points covered in this section, discuss the risks and benefits of hormone replacement therapy with your doctor.

3. How to take Tibocina

Always take this medicine exactly as instructed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
When you can start taking Tibocina

If you are switching to Tibocina while using another type of HRT
There are several types of HRT, for example tablet formulations, patches, and gels.
Most of these contain oestrogen or a combination of oestrogen and progestogen. It is common that with some types of HRT you may still have menstrual bleeding, while with others you do not; the latter are referred to as "HRT without menstruation".

What to consider when starting treatment with Tibocina
If you have reached natural menopause, you should start taking Tibocina no earlier than 1 year after your last natural menstrual period. However, if your ovaries have been surgically removed, you can start taking Tibocina immediately.

If you wish to start taking Tibocina and have experienced irregular or unexpected vaginal bleeding, contact your doctor before starting treatment with Tibocina, so that any malignant condition can be ruled out.

If you wish to switch to Tibocina from a medication containing an oestrogen and a progestogen, consult your doctor for advice on what needs to be considered.

How much Tibocina to take and when
Unless otherwise prescribed by your doctor, the recommended dose is:
one tablet daily, taken preferably at the same time each day.
Your doctor will prescribe the lowest effective dose needed to treat your symptoms for the shortest possible duration. If you feel this dose is too strong or too weak, consult your doctor.
Do not take a progestogen preparation in addition to Tibocina.

How to take Tibocina
Swallow the tablets with a glass of water or another drink, preferably at the same time each day.

If you are scheduled for surgery
If you are about to undergo surgery, inform your surgeon that you are taking Tibocina. You may need to stop taking Tibocina approximately 4–6 weeks before the surgery to reduce the risk of a 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
Severe symptoms are unlikely, even if you take more than one tablet at the same time. In case of acute overdose, you may feel unwell (nausea), be sick (vomiting), and vaginal bleeding may occur. If necessary, contact your doctor so these symptoms can be treated.

If you forget to take Tibocina
If you forget to take a tablet at your usual time, take it as soon as possible, unless more than 12 hours have passed since the missed dose. In that case, skip the forgotten tablet and take the next tablet at your usual time. Do not take a double dose to make up for a forgotten tablet.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them. Most side effects are mild.
The following conditions are reported more frequently in women receiving hormone replacement therapy compared to women not receiving hormone replacement therapy:

• breast cancer
• abnormal growth or tumour of the uterine lining (endometrial hyperplasia or endometrial cancer)
• ovarian cancer
• blood clots in the veins of the legs or lungs (venous thromboembolism)
• heart diseases
• stroke
• possible memory loss if hormone replacement therapy is started after the age of 65.

For further information on these side effects, see section 2.
Tell your doctor or pharmacist if you are concerned about any side effects you think may be due to Tibocina (see also section 2 “Stop taking Tibocina and contact your doctor immediately”).
Serious side effects – contact your doctor immediately
If you think you are experiencing signs of a serious side 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 yellowish (jaundice)
• if you suddenly develop severe headaches resembling migraines (see section 2 above)
• if you experience signs of a blood clot (see section 2 above)
• if any of the conditions listed in section 2 (“Do not take Tibocina”) occur

Other side effects
Common (affects up to 1 in 10 women):

• breast tenderness or pain
• stomach or pelvic pain
• unusual hair growth
• vaginal bleeding or spotting. This is generally not a cause for concern during the first few months of hormone replacement therapy. If bleeding continues or starts after hormone replacement therapy has been ongoing for some time, see section 2.
• vaginal problems, such as increased discharge, itching, irritation, and candidiasis
• thickening of the uterine lining or cervical lining
• weight gain

Uncommon (affects up to 1 in 100 women):

• swelling of hands, ankles or feet – a sign of fluid retention
• stomach discomfort
• acne
• nipple pain or breast discomfort
• vaginal infections

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

• skin itching

Some women taking Tibocina have also reported:

• depression, dizziness, headache
• joint or muscle pain
• skin disorders, such as rashes
• loss of vision or blurred vision
• changes in liver function tests

Cases of breast cancer and increased cell growth or tumours of the uterine lining have been reported in women using Tibocina.
→ If any of the side effects described above persist or become troublesome, inform your doctor.
The following side effects have been reported with other hormone replacement therapies:

• gallbladder disease
• various skin disorders:
• skin discolouration, especially on the face or neck, a condition known as “pregnancy mask” (chloasma)
• red, painful skin nodules (erythema nodosum)
• rash with redness or irritation in a target-like pattern (erythema multiforme)

If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazione-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Tibocina

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton/blister after the words
EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Tibocina contains
The active substance is tibolone.
Each tablet contains 2.5 mg of tibolone.
The other components are:
potato starch, monohydrate lactose, magnesium stearate (vegetable), ascorbyl palmitate.

Description of the appearance of Tibocina and package contents
Tibocina is available as round, flat tablets, white to almost white in colour, approximately 6 mm in diameter, packed in PVC/PVDC/Al blisters.
Tibocina is available in pack sizes of 1 x 28 tablets, 1 x 30 tablets and 3 x 28 tablets.

Marketing Authorization Holder
Sandoz S.p.A.
L.go U. Boccioni 1
21040 Origgio (VA)
Italy

Manufacturers
Aristo Pharma GmbH, Wallenroder Straße 8-10, 13435 Berlin, Germany
Salutas Pharma GmbH, Otto-von-Guericke-Allee 1, 39179 Barleben, Germany

This medicinal product is authorized in the European Economic Area countries under the following names:
Denmark: Tibocina
Finland: Tibocina 2.5 mg tabletti
Italy: Tibocina 2.5 mg compresse
Norway: Tibocina 2.5 mg tabletter
Sweden: Tibolinia 2.5 mg tablett