TIBOLONE ARISTO 2.5 mg TABLETS

2. What you need to know before you take Tibolona Aristo

Medical history and regular check-ups

The use of HRT or tibolone involves risks that need to be considered when deciding to start or continue treatment.

Treatment experience in women with premature menopause (due to ovarian failure or surgery) is limited. If you have premature menopause, the risk of using HRT or tibolone may be different. Consult your doctor.

Before starting (or restarting) HRT or tibolone, your doctor will ask about your personal and family medical history and may decide to perform a medical examination, including a breast examination and/or internal examination if necessary.

Once treatment with tibolone has started, you should visit your doctor for regular medical check-ups (at least once a year). During these check-ups, the benefits and risks of continuing treatment with tibolone will be assessed.

Attend regular breast examinations as recommended by your doctor.

In addition, it is recommended to participate in early detection programs through mammography. It is important to inform the healthcare professional performing the mammography that you are being treated with HRT, as this medication may increase the density of your breasts and may affect the test result. When breast density is increased, mammography may not detect lumps.

Do not take Tibolona Aristo

If you have any of the following conditions. If you are unsure, consult your doctorbefore taking tibolone

• if you have or have had breast cancer, or if you suspect you may have it.
• if you have estrogen-sensitive cancer, 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 abnormal growth of the lining of the uterus(endometrial hyperplasia), and are not being treated.
• if you have or have had a blood clot(thrombosis) in the legs (deep vein thrombosis) or lungs (pulmonary embolism).
• if you have a blood clotting disorder(such as protein C or protein S, or antithrombin deficiency).
• if you have or have had a blood clot-related disease, such as a heart attack, stroke, or angina.
• if you have or have had liver diseaseand liver function has not returned to normal.
• if you have a rare blood disordercalled porphyria, which 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 any of the above conditions occur for the first time while taking tibolone, stop taking it and consult your doctor immediately.

Warnings and precautions

Consult your doctor before starting tibolone.

Before starting treatment, consult your doctor if you have or have had any of the following conditions, as they may come back or get worse during treatment with tibolone. If so, you may need to have more frequent check-ups:

• uterine fibroids.
• 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 developing blood clots (see "Blood clots in a vein (thrombosis)").
• high risk of developing 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 headache.
• a disease that affects the immune system and many 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 heart or kidney problems.

Stop taking Tibolona Aristo and consult your doctor immediately

If you notice any of the following symptoms while taking HRT or tibolone:

• any of the conditions listed in the "Do not take Tibolona Aristo" section.
• yellowing of the skin or the whites of the eyes (jaundice). These may be signs of liver disease.
• a significant increase in blood pressure (some symptoms may be headache, fatigue, dizziness).
• unexplained migraine-like headaches that occur for the first time.
• if you become pregnant.
• if you notice symptoms of a blood clot, such as:

1. - painful swelling and redness in the legs
2. - sudden chest pain
3. - difficulty breathing

For more information, see "Blood clots in a vein (thrombosis)".

Note:Tibolona is not a contraceptive. If you have been postmenopausal for less than 12 months or are under 50 years of age, you may need to take additional contraceptive measures to prevent pregnancy. Consult your doctor.

HRT and Cancer

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

Observational studies have consistently shown that women taking tibolone have a higher risk of developing endometrial cancer. This risk increases with the duration of treatment.

Irregular bleeding

You may experience irregular bleeding or spotting during the first 3 to 6 months of treatment with Tibolona. If the bleeding or spotting:

• lasts more than the first six months
• starts after you have been taking tibolone for more than six months.
• continues after you have stopped taking tibolone

consult your doctor immediately.

Breast Cancer

Available data show that the use of tibolone increases the risk of breast cancer. The additional risk depends on the duration of use of 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 taking combined HRT and a similar risk to women taking estrogen-only HRT.

Examine 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

Ovarian Cancer

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

The risk of ovarian cancer varies with age. For example, in women between 50 and 54 years of age who are not taking HRT, about 2 cases of ovarian cancer per 2,000 women may be expected over a 5-year period. In women who have taken HRT for 5 years, about 3 cases per 2,000 patients (i.e., about 1 additional case) may be expected.

The increased risk of ovarian cancer with the use of tibolone is similar to the risk with other types of HRT.

Effects of HRT on the heart and circulation

Blood clots in a vein (thrombosis)

The risk of developing blood clots in the veins is 1.3 to 3 times higher in women taking HRT than in non-users, especially during the first year of treatment.

Blood clots can be serious and if one reaches the lungs, it can cause chest pain, difficulty breathing, fainting, and even death.

You are more likely to get a blood clot if you are older and if you are in any of the following situations, in which case you should inform your doctor:

• if you are taking estrogens.
• if you are unable to walk for a long time due to major surgery, injury, or illness (see also section 3, If you need surgery). The risk of a blood clot may be temporarily increased due to prolonged immobilization (e.g., bedridden, leg cast), severe injury, or prolonged surgery. In patients using HRT, as with all patients, after surgery, precautions should be taken to prevent a blood clot.
• if you are significantly overweight (BMI >30 kg/m2).
• if you have a blood clotting disorder that requires long-term treatment with a medicine to prevent blood clots.
• if any of your close relatives have had a blood clot in the leg, lung, or other organ.
• if you have systemic lupus erythematosus (SLE).
• if you have cancer.

In case of symptoms of a blood clot, see "Stop taking Tibolona Aristo and consult your doctor immediately".

Comparison

Between 4 and 7 out of 1,000 women, with an average age of 50 years, not taking HRT, may develop a blood clot over a period of 5 years or more.

Between 9 and 12 out of 1,000 women, with an average age of 50 years, taking combined estrogen-progestogen HRT for 5 years or more, may develop a blood clot.

The increased risk of developing a blood clot with the use of tibolone is lower than with other types of HRT.

Heart disease (heart attack)

There is no evidence that hormone replacement therapy (HRT) or tibolone can prevent a heart attack.

Women over 60 years of age who use combined estrogen-progestogen HRT are slightly more likely to develop heart disease than those not taking HRT. As the risk of heart disease depends largely on age, the number of additional cases of heart disease due to combined estrogen-progestogen HRT is very low in healthy women close to menopause, but will increase with age.

There is no evidence to suggest that the risk of heart attack with tibolone is different from the risk with other HRT.

Stroke

The risk of having a stroke is 1.5 times higher in women taking HRT than in non-users. The risk due to HRT increases with age.

Comparison

Three out of 1,000 women, with an average age of 50 years, not taking tibolone, may have a stroke over a 5-year period. The figure would be 7 out of 1,000 women taking tibolone, with an average age of 50 years, over the same period.

In the case of women in their sixties(60 to 69 years) who are not taking tibolone, it can be expected that 11 out of 1,000women may have a stroke. In those taking tibolone, it would be 24 out of 1,000women who may have a stroke.

Other diseases

• Hormone replacement therapy (HRT) does not prevent memory loss. There is evidence of a higher risk of memory loss in women who start HRT after the age of 65. Consult your doctor.
• Treatment with tibolone causes changes in cholesterol levels.
• Patients with heart or kidney failure: Estrogens may cause fluid retention, and patients with heart or kidney failure should be carefully monitored.
• Patients with high levels of fat in the blood (hypertriglyceridemia): Women with pre-existing hypertriglyceridemia should be closely monitored during treatment with tibolone, as rare cases of significant increases in plasma triglycerides have been reported, leading to pancreatitis with estrogen therapy in this condition.

Other medicines and Tibolona Aristo

Some medicines may interfere with the effects of tibolone and cause irregular bleeding. The following medicines may have this effect:

• medicines to prevent blood clots (such as warfarin)
• medicines for epilepsy (such as phenobarbital, phenytoin, and carbamazepine)
• medicines for tuberculosis (such as rifampicin or rifabutin)
• herbal products containing St. John's Wort (Hypericum perforatum).

HRT may affect the way other medicines work:

A medicine for epilepsy (lamotrigine), as it may increase the frequency of seizures.

Concomitant use with tibolone may increase the effect of anticoagulants (medicines that prevent blood clotting).

Concomitant use with tibolone may have an influence on medicines with active substances (e.g., midazolam) that are metabolized by certain enzymes (the so-called cytochrome-P450 enzymes).

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

Your doctor will advise you.

Lab tests

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

Pregnancy and breast-feeding

Do not take tibolone if you are pregnant or breast-feeding.

Tibolona is indicated only for postmenopausal women. If you are pregnant, stop taking tibolone and consult your doctor.

Driving and using machines

Tibolona does not affect the ability to drive or use machines.

Tibolona Aristo containslactose monohydrate

If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to take Tibolona Aristo

Follow exactly the administration instructions of this medication indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

How much Tibolona Aristo should you take and for how long

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

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

Do not take a progestogen preparation in addition to tibolona.

How to take Tibolona Aristo

Take the tablets with a little water or another drink, preferably at the same time every day.

What to consider when starting treatment with Tibolona Aristo

If you had a natural menopause, you should start taking tibolona one year after your last menstrual bleeding. If you have had your ovaries removed by surgery, you can start taking tibolona immediately.

If you think you will take tibolona and have had irregular or unexpected vaginal bleeding, please consult your doctor before starting treatment with tibolona so that the possibility of any malignant disease can be ruled out.

If you want to change from another medication to tibolona and were previously taking a medication with estrogens and progestogens, please consult your doctor what you should consider.

How long you should take Tibolona Aristo

Your doctor will aim for the treatment to be as short as possible.

Generally, an improvement in symptoms is achieved within a few weeks.

If you take more Tibolona Aristo than you should

If you have taken more tibolona, you should contact your doctor or pharmacist immediately.

It is unlikely that symptoms of intoxication will occur even if several tablets are ingested at the same time. In case of acute overdose, nausea, vomiting, and intermenstrual bleeding may occur. 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 medication and the amount ingested.

If you forget to take Tibolona 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 time you should have taken it. If more than 12 hours have passed, do not take the missed tablet and take the next tablet at the usual time.

Do not take a double dose to make up for missed doses.

If you need surgery

If you are going to undergo surgery, tell the surgeon that you are taking tibolona. You may need to stop taking tibolona 4 to 6 weeks before surgery to reduce the risk of a blood clot (see section 2, "Blood clots in the veins (thrombosis)"). Ask your doctor when you can start taking tibolona again.

If you have doubts about the use of tibolona, consult your doctor or pharmacist.

4. Possible side effects

The following diseases occur more frequently in women who follow HRT (Hormone Replacement Therapy) compared to those who do not:

• Breast cancer
• Abnormal growth or cancer of the uterine lining (endometrial hyperplasia or cancer)
• Ovarian cancer
• Blood clots in the veins of the legs or lungs (venous thromboembolism)
• Heart disease
• Stroke
• Probable memory loss if HRT started at an age over 65.

For more information on side effects, see section 2 "What you need to know before taking Tibolona Aristo".

Like all medications, tibolona can cause side effects, although not all people experience them.

Consult your doctor or pharmacistif you are concerned about any of the side effects that you think may be caused by tibolona, see also section 2 "Stop taking Tibolona Aristo and consult your doctor immediately".

Frequent(may affect 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
• Vaginal yeast infection (e.g., candidiasis)
• Pelvic pain
• Changes in the cervical tissue
• Inflammation of the lips and vagina (called vulvovaginitis)
• Abnormalities in the cervical smear

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

• Acne
• Pain in the nipples or breasts
• Fungal infections

Other side effects reported with Tibolona Aristo since marketing:

• Dizziness, headache, migraine
• Depression
• Skin problems such as rashes
• Loss of vision or blurred vision
• Abdominal or intestinal discomfort
• Fluid retention
• Pain in the joints or muscles
• Changes in liver function laboratory tests

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

With other Hormone Replacement Therapies, the following side effects have been reported:

• Gallbladder disease
• Skin disorders:
  • Discoloration of the skin, especially on the face and neck, known as "pregnancy spots" (chloasma)
  • Painful red nodules on the skin (erythema nodosum)
  • Rash with redness or ulcers (erythema multiforme)
  • Bleeding from the skin (vascular purpura)

Talk to your doctor if you have irregular or unusual vaginal bleeding or if you have one of the side effects mentioned above or if they worsen.

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 is not listed in this leaflet. You can also report them directly through the Spanish Medicines and Healthcare Products Agency: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Tibolona Aristo

Keep this medication out of 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.

No special storage conditions are required.

Do not use this medication if you notice that the blister is damaged.

Medications should not be thrown away in drains or trash. Deposit the packaging and medications you no longer need at the SIGRE point in the pharmacy. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Tibolona Aristo

• The active ingredient is Tibolona.

Each tablet contains 2.5 mg of tibolona.

• The other ingredients are:

potato starch, magnesium stearate (vegetable origin), ascorbyl palmitate, and lactose monohydrate.

Appearance of the product and package contents

Tibolona Aristo is presented in white or almost white, round tablets, approximately 6 mm in diameter.

Tibolona Aristo is available in packs of 1x28 tablets, 1x30 tablets, and 3x28 tablets.

Not all packs may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Aristo Pharma GmbH

Wallenroder Str. 8-10

13435 Berlin, Germany

Manufacturer

Aristo Pharma GmbH Wallenroder Str. 8-10

13435 Berlin, Germany

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Aristo Pharma Iberia, S.L.

C/ Solana, 26

28850, Torrejón de Ardoz

Madrid, Spain

Date of the last revision of this leaflet:November 2023.

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS) http://www.aemps.es/