Package leaflet: Information for the user

Tibolone Aristo 2.5 mg tablets

tibolone
Generic 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 other people, even if they have the same symptoms as you, because it may 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:

What Tibolone Aristo is and what it is used for
What you need to know before taking Tibolone Aristo
How to take Tibolone Aristo
Possible side effects
How to store Tibolone Aristo
Contents of the pack and other information

1. What Tibolone Aristo is and what it is used for

Tibolone Aristo is a Hormone Replacement Therapy (HRT). Tibolone Aristo contains the active substance tibolone, a synthetic sex hormone. Tibolone Aristo is indicated in women who are postmenopausal, i.e. at least 12 months after their last natural menstrual period.
Tibolone Aristo 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 symptoms such as a feeling of warmth in the face, neck, and chest ("hot flushes"). Tibolone Aristo relieves these postmenopausal symptoms. Your doctor will prescribe Tibolone Aristo only if these symptoms seriously impair your normal daily activities.

2. What you should know before taking Tibolone Aristo

Medical history and regular check-ups
Hormone replacement therapy (HRT) or treatment with Tibolone Aristo involves certain risks, which
should be considered when deciding whether to start or continue taking this medicine.
Experience in treating women who have entered menopause prematurely (due to ovarian failure or
surgical intervention) is limited. If you have experienced premature menopause, the risks associated with
HRT or the use of Tibolone Aristo may differ. Please consult your doctor.
Before starting (or restarting) hormone replacement therapy or taking Tibolone Aristo, your doctor will
discuss your personal and family medical history with you. Your doctor may also decide to perform a
physical examination, which could include a breast examination and/or an internal pelvic examination, if
necessary.
Once you have started treatment with Tibolone Aristo, you must visit your doctor regularly (at least once
a year). During these visits, discuss with your doctor the benefits and risks of continuing therapy with
Tibolone Aristo.
Undergo regular mammographic screening as recommended by your doctor.
You are also advised to participate in mammographic screening programs when offered. For mammographic
screening, it is important to inform the nurse/healthcare professional performing the X-ray that you are
currently undergoing HRT, as this medication may increase breast density, which can affect the outcome of
the mammogram. Increased breast density may make it more difficult for mammography to detect all lumps.

Do not take Tibolone Aristo
If any of the conditions listed below apply to you. If you have any doubts about any of the following points,
consult your doctor before taking Tibolone Aristo.
If you have or have ever had breast cancer, or suspect you may have it
If you suffer from a form of cancer sensitive to oestrogens, such as cancer of the lining of the
uterus (endometrium), or suspect you may have it
If you have unexplained vaginal bleeding
If you have excessive thickening of the uterine lining (endometrial hyperplasia) that has not been
treated
If you have or have ever had a blood clot in a vein (thrombosis), for example in the legs (deep
venous 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 a disease caused by blood clots in the arteries,
such as heart attack, stroke or angina
If you suffer from or have previously suffered from liver disease and liver function test results
have not returned to normal
If you suffer from a rare inherited blood disorder called "porphyria" (a hereditary disease)
If you are allergic (hypersensitive) to tibolone or to any of the other ingredients of Tibolone
Aristo (listed in section 6)
If you are pregnant or think you may be pregnant
If you are breastfeeding

If any of the above conditions occurs for the first time during treatment with Tibolone Aristo, stop taking
the medicine immediately and consult your doctor without delay.

Warnings and precautions
Talk to your doctor or pharmacist before taking Tibolone Aristo.
Before starting treatment, inform your doctor if you suffer or have ever suffered from any of the
following conditions, as they may reappear or worsen during treatment with Tibolone Aristo. In such
cases, your doctor may need to perform more frequent check-ups:
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 oestrogen-sensitive cancer (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 fat (triglycerides) in the blood
heart problems
kidney problems

Stop taking Tibolone Aristo and consult your doctor immediately if:
During hormone replacement therapy or while taking Tibolone Aristo, you notice any of the following:
any of the conditions listed in the section "Do not take Tibolone Aristo"
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: Tibolone Aristo 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. Please consult your doctor for advice.

HRT and Cancer

Excessive thickening of the uterine lining (endometrial hyperplasia) and cancer of the lining of the
uterus (endometrial carcinoma)
Observational studies have consistently shown that women treated with tibolone have an increased
risk of being diagnosed with cancer of the uterine lining. This risk increases with longer duration of
treatment.

Irregular bleeding
During the first 3–6 months of treatment with Tibolone Aristo, you may experience irregular bleeding or
light spotting. If bleeding or spotting:
persists beyond the first 6 months
starts after you have been taking Tibolone Aristo for more than 6 months
continues after you have stopped taking Tibolone Aristo
→ consult your doctor as soon as possible.

Breast cancer
Evidence shows that taking tibolone increases the risk of breast cancer. The additional risk depends on
the duration of tibolone use. In HRT studies, after stopping HRT, the additional risk decreased over time,
but the risk may persist for 10 years or more if HRT has been used for more than 5 years. Regarding
tibolone, data on the persistence of risk after discontinuation are not available, but a similar pattern
cannot be excluded.

Comparison
Women taking Tibolone Aristo have a lower risk compared to women on combined HRT and a similar risk
to those on oestrogen-only HRT.

Check your breasts regularly. Consult your doctor as soon as possible if you notice any changes,
such as:
dimpling or indentations of the skin
changes in the nipple
any visible or palpable lumps

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 50–54 years not using HRT,
about 2 in 2,000 will be diagnosed with ovarian cancer over a 5-year period. Among women using HRT for
5 years, about 3 in 2,000 women will be diagnosed (i.e. about 1 additional case).

With the use of Tibolone Aristo, the increase in risk of ovarian cancer is similar to that of other types of
HRT.

Effects of HRT on the heart and circulation

Blood clots in a vein (thrombosis)
The risk of venous blood clots is approximately 1.3 to 3 times higher in women using HRT compared to
non-users, especially during the first year of treatment.

Blood clots can be serious and, if they travel to the lungs, can cause chest pain, shortness of breath,
fainting, or even death.

Your risk 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 taking oestrogens
if you are unable to walk for long periods due to major surgery, trauma or illness (see also section 3,
"In case of surgery"). The risk of thromboembolic disease may be temporarily increased due to
prolonged immobilisation (e.g. bed rest, leg fracture), severe injury or long surgical procedures. In
patients using HRT, as with all patients, appropriate preventive measures must be carefully followed
after surgery to prevent venous thromboembolic disease.
if you are severely overweight (BMI >30 kg/m²)
if you have 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 cancer.

For signs of a blood clot, see the section "Stop taking Tibolone Aristo and consult your doctor immediately".

Comparison
Among women aged 50 not using HRT, it is expected that, on average, between 4 and 7 out of 1,000 will
develop a venous blood clot over a 5-year period.
Among women aged 50 using oestrogen-progestin HRT 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 Tibolone Aristo, the increase in the risk of developing a venous blood clot is lower than
with other types of HRT.

Heart disease (heart attack)
There is no evidence that HRT or Tibolone Aristo prevent heart attacks.
Women over 60 years of age using oestrogen-progestin HRT have a slightly higher risk of developing heart
disease compared to those not using HRT.
Although the risk of heart disease strongly depends on age, the number of additional cases of heart
disease 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 tibolone use differs from that
with other HRT treatments.

Stroke
The risk of stroke is approximately 1.5 times higher in women using HRT compared to non-users. The number
of additional stroke cases due to HRT use increases with age.

Comparison
Among women aged 50 not taking tibolone, it is expected that, on average, 3 out of 1,000 will have a
stroke over a 5-year period. Among women aged 50 taking tibolone, this number rises to 7 out of 1,000
(i.e. 4 additional cases).
Among women aged 60 not taking tibolone, it is expected that, on average, 11 out of 1,000 will have
a stroke.
Among women aged 60 taking tibolone, this number rises to 24 out of 1,000 (i.e. 13 additional cases).

Other conditions
HRT does not prevent memory loss. There is some evidence of an increased risk of memory loss in
women who start HRT after age 65. Consult your doctor for advice.
Treatment with tibolone causes changes in cholesterol levels.
Patients with heart or kidney dysfunction: oestrogens may cause fluid retention; therefore, patients with
cardiac or renal dysfunction should be closely monitored.
Women with lipid metabolism disorders (hypertriglyceridaemia): women with pre-existing
hypertriglyceridaemia should be closely monitored during tibolone therapy, as rare cases of significant
increases in plasma triglycerides and subsequent pancreatitis have been reported with oestrogen therapy.

Other medicines and Tibolone Aristo
Some medicines may interfere with the effect of Tibolone Aristo. 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 tuberculosis (such as rifampicin or rifabutin)
herbal remedies containing St John's wort (Hypericum perforatum).

HRT may affect how some other medicines work:
Concomitant use of tibolone may increase the effect of anticoagulants (medicines against blood clotting).
Concomitant use with tibolone may influence medicines containing active substances (e.g. midazolam) that
are metabolised by certain enzymes (so-called cytochrome-P450 enzymes).
Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including
over-the-counter medicines, herbal remedies or other natural products.
Your doctor will advise you.

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

Pregnancy and breastfeeding
Do not take Tibolone Aristo if you are pregnant or breastfeeding.
Tibolone Aristo is intended only for postmenopausal women. If you become pregnant, stop taking
Tibolone Aristo and consult your doctor.

Driving and using machines
Tibolone Aristo has no known effect on the ability to drive or use machines.

Tibolone Aristo contains lactose monohydrate
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this
medicine.

For athletes: using this medicine without therapeutic need constitutes doping and may result in a positive
anti-doping test.

3. How to take Tibolone Aristo

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
How much Tibolone Aristo should you take and how often
Your doctor will prescribe the lowest effective dose needed to treat your symptoms, for the shortest possible duration. Talk to your doctor if you think this dose is too strong or not strong enough.
Unless otherwise prescribed by your doctor, the recommended dose is:
One tablet daily after a meal, preferably at the same time each day.
Do not take a progestogen preparation in addition to Tibolone Aristo.
How to take Tibolone Aristo
Swallow the tablets with a glass of water or another drink, preferably at the same time each day.
What to consider when starting treatment with Tibolone Aristo
If you have undergone natural menopause, you should start taking Tibolone Aristo no sooner than 1 year after your last natural menstrual period. If your ovaries have been surgically removed, you may start taking Tibolone Aristo immediately.
If you wish to start taking Tibolone Aristo and have experienced irregular or unexpected vaginal bleeding, contact your doctor before starting treatment with Tibolone Aristo, so that any malignant condition can be ruled out.
If you wish to switch to Tibolone Aristo from a medicine containing an oestrogen and a progestogen, consult your doctor for advice on what needs to be considered.
How long should you take Tibolone Aristo
Your doctor will ensure that your treatment is as short as possible.
Symptom improvement is usually achieved within a few weeks.
If you take more Tibolone Aristo than you should
If you have taken an excessive dose of Tibolone Aristo, contact your doctor or pharmacist immediately.
Symptoms of toxicity are unlikely, even if you take more than one tablet at a time. In case of acute overdose, you may experience nausea, vomiting, and withdrawal bleeding. Contact your doctor so that these symptoms can be managed.
If you forget to take Tibolone Aristo
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 need to undergo surgery
If you are about to undergo surgery, inform your surgeon that you are taking Tibolone Aristo.
You may need to stop taking Tibolone Aristo approximately 4–6 weeks before the surgery to reduce the risk of blood clots (see section 2, “Blood clots in a vein”). Ask your doctor when you can restart taking Tibolone Aristo.
If you have further questions about the use of Tibolone Aristo, ask your doctor or pharmacist.

4. Possible side effects

The following conditions are reported more frequently in women receiving hormone replacement therapy compared to women not taking it:

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 disease
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 “What you should know before taking Tibolone Aristo”.

Like all medicines, Tibolone Aristo can cause side effects, although not everyone experiences them.

Tell your doctor or pharmacist if you are concerned about any side effects you think may be due to Tibolone Aristo (see also section 2 “Stop taking Tibolone Aristo and contact a doctor immediately”).

Common side effects observed in clinical studies (affecting up to 1 in 10 women):

vaginal bleeding or spotting
stomach pain
weight gain
breast pain
unusual hair growth
vaginal problems such as increased discharge, itching, and irritation
thickening of the uterine lining
fungal vaginal infection (e.g. candidiasis)
pelvic pain
cervical tissue changes
inflammation of the lips and vagina (so-called vulvovaginitis)
cervical smear abnormalities

Uncommon side effects (affecting up to 1 in 100 women):

acne
painful nipples or breasts
fungal infections

Other side effects reported with Tibolone Aristo after its marketing:

dizziness, headache, migraine
depression
skin problems such as rash or itching
loss of vision or blurred vision
stomach ache or intestinal disturbances
fluid retention
joint pain or muscle pain
changes in liver function tests

Cases of uterine lining cancer, breast cancer, and stroke have been reported in women using Tibolone Aristo (see "Warnings and precautions" in section 2).

The following side effects have been reported with other hormone replacement therapies:

gallbladder disease
various skin disorders:
- skin discolouration, particularly on the face or neck, a condition known as "pregnancy spots" (chloasma)
- painful, reddish skin nodules (erythema nodosum)
- skin rash with redness or target-shaped lesions (erythema multiforme)
- skin bleeding (vascular purpura)

Talk to your doctor if you experience irregular vaginal bleeding or spotting, or if you develop any of the side effects listed above, or if they worsen.

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

5. How to store Tibolone Aristo

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 "Exp.".
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not use this medicine if you notice that the blister is damaged.
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 Tibolone Aristo contains

The active substance is Tibolone. Each tablet contains 2.5 mg of tibolone.
The other ingredients are: potato starch, monohydrate lactose, magnesium stearate (Ph.Eur.) [of vegetable origin], ascorbyl palmitate (Ph.Eur.)

Description of the appearance of Tibolone Aristo and contents of the pack
Tibolone Aristo is presented as round, flat tablets, white to almost white in colour, with a diameter of approximately 6 mm.
Tibolone Aristo is available in packs of 1x28 tablets, 1x30 tablets and 3x28 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Aristo Pharma GmbH
Wallenroder Straße 8-10
13435 Berlin
Germany

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Belgium Tibolone Aristo 2.5 mg tabletten/comprimés/Tabletten
Finland Tibolon Aristo 2.5 tabletit
Ireland Tibolone Aristo 2.5 mg tablets
Italy Tibolone Aristo
Norway Tibolon Oresund Pharma 2.5 mg tabletter
Poland Tibolone Aristo
Slovakia Tibolónu Aristo 2.5 mg tablety
Spain Tibolona Aristo 2.5 mg comprimidos EFG
Sweden Tibolon Oresund Pharma 2.5 mg tabletter
United Kingdom Tibolone 2.5 mg tablets
Czech Republic Tibolon Aristo