Package Leaflet: Information for the User

Tibolona Aristo 2.5 mg Tablets EFG

Read this 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. Do not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What isTibolona Aristoand what it is used for

2. What you need to know before you start takingTibolona Aristo

3. How to takeTibolona Aristo

4. Possible side effects

5. Storage ofTibolona Aristo

6. Contents of the pack and additional information

Tibolona belongs to the group of medications for Hormonal Replacement Therapy (HRT)(HRT).It contains tibolona, a synthetic sex hormone.Tibolona Aristo is indicated in postmenopausal women in whom at least 12 months have elapsed since their last natural period.

Tibolona 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 symptoms such as sweating and hot flashes. Tibolona relieves these symptoms after menopause. Tibolona will only be prescribed if the patient's symptoms seriously hinder their daily life.

Medical History and Regular Check-Ups

The use of THS or tibolona involves risks that need to be considered when making the decision to start or continue treatment.

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

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

Once treatment with tibolona has begun, 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 tibolona will be evaluated.

Attend regular check-ups for your breasts as recommended by your doctor.

Additionally, it is recommended to participate in early detection programs through mammography. It is essential to inform the healthcare professional performing the mammography that you are taking THS, as this medication can increase the density of your breasts and affect the test results. When breast density is increased, mammography may not detect lumps.

Do Not Take Tibolona Aristo

If you have any of the following symptoms, consult your doctor before taking tibolona.Consult your doctorif you have any doubts.

• If you have or have hadbreast cancer, or if you suspect you may have it.
• If you havecancer that is sensitive to estrogen, such as endometrial cancer or if you suspect you may have it.
• If you experienceunexplained vaginal bleeding.
• If you haveabnormal growth of the layer that covers the uterus(endometriosis), and are not being treated.
• If you have or have hadblood clots in the blood (thrombosis)in the legs (deep vein thrombosis) or lungs (pulmonary embolism).
• If you have anyalteration in blood clotting(such as protein C or protein S, or antithrombin).
• If you have or have hadarterial disease caused by blood clots, such asheart attack, stroke, or angina.
• If you have or have hadliver diseaseand liver function has not returned to normal.
• If you have arare blood disordercalled “porphyria” that is inherited.
• If you areallergic(hypersensitive) to tibolona or any of the other components of this medication (including those listed in section 6).
• If you arepregnantor suspect you may be.
• If you arebreastfeeding.

If any of the above effects appear for the first time while taking tibolona, stop taking it and consult your doctor immediately.

Warnings and Precautions

Consult your doctor before starting to take tibolona.

Before starting treatment, consult your doctor if you have or have had any of the following symptoms, as they may recur or worsen during treatment with tibolona. If so, you should undergo more frequent medical check-ups:

• Fibroids in the uterus.
• Abnormal growth of the layer that covers the uterus (endometriosis) or history of abnormal growth of the layer that covers the uterus (endometrial hyperplasia).
• High risk of developing blood clots (see “Blood clots in a vein (thrombosis)”).
• High risk of developing cancer that is dependent on estrogen (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.
• Galstones.
• Migraine or severe headache.
• A disease of the immune system that affects many organs in 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 cardiac or renal problems.

Stop Taking Tibolona Aristo and Consult Your Doctor Immediately

If you notice any of the following symptoms while taking THS or tibolona:

• Any of the situations mentioned in the section “Do Not Take Tibolona Aristo”.
• Yellowing of the skin or white of the eyes (jaundice). This could be a sign of liver disease.
• Significant increase in blood pressure (some symptoms may include headache, fatigue, dizziness).
• Unexplained migraines or severe headaches.
• Getting pregnant.
• Noticing symptoms of blood clots such as:

1. - Swelling and pain in the legs
2. - Sudden chest pain
3. - Difficulty breathing

See “Stop Taking Tibolona Aristo and Consult Your Doctor Immediately” for more information.

Note:Tibolona is not a contraceptive. If you have had your last natural menstrual period less than 12 months ago or are under 50 years old, you may need to take additional contraceptive measures to prevent pregnancy. Consult your doctor for advice.

THS and Cancer

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

Observational studies have consistently shown that users of tibolona have a higher risk of developing endometrial cancer. This risk increases with the longer 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 six months
• Begins after taking tibolona for more than six months.
• Continues even after stopping tibolona

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 THS, after stopping THS, the additional risk decreased over time, but the risk may persist for 10 years or more in women who have used THS for more than 5 years. It cannot be ruled out that a similar pattern may occur with tibolona, but there is no data on the persistence of risk after stopping tibolona.

Comparison

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

Check Your Breasts Regularly. Consult Your Doctor If You Notice:

• Indentations 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 THS with estrogen alone or with a 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 taken THS, about 2 cases of ovarian cancer per 2,000 women have been observed over a 5-year period. In women who have taken THS for 5 years, about 3 cases per 2,000 patients have been observed (i.e., about 1 additional case).

The increased risk of ovarian cancer with tibolona is similar to the risk with other types of THS.

Effects of THS on the Heart and Circulation

Blood Clots in a Vein (Thrombosis)

The risk of developing blood clots in the veins is between 1.3 and 3 times higher in women using Hormone Replacement Therapy (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 develop 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 estrogen.
• If you are unable to walk for a prolonged period due to surgery, injury, or illness (see also section 3, If You Need Surgery).The riskof a thromboembolic diseasemay increase temporarily due toprolonged immobility(e.g., being bedridden, leg casted),serious injuriesorlong-term surgeries.Inpatients usingHRT, aswithall patients,after surgery, careful precautions should be taken to prevent a venous thromboembolic disease.
• If you have a significant overweight (BMI >30 kg/m2).
• If you have problems with blood clotting that require long-term treatment with a medication 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.

If you experience symptoms of blood clots, see “Stop Taking Tibolona Aristo and Consult Your Doctor Immediately”.

Comparison

Between 4 and 7 out of every 1,000 women, aged 50, who are not taking tibolona, may develop a blood clot in the veins over a 5-year period or more.

Between 9 and 12 out of every 1,000 women, aged 50, who have been taking combined estrogen-progestogen THS for 5 years or more, may develop a blood clot in the veins.

The increased risk of developing a blood clot with tibolona is lower than with other types of THS.

Heart Disease (Heart Attack)

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

Women over 60 who use combined estrogen-progestogen HRT are slightly more likely to develop heart disease than those who do not use HRT.Asthe riskof heart diseasedepends to a large extent onage,the number ofadditional cases ofheart diseasedue to HRTis very lowin healthy womenaroundmenopause, butwill increaseas age advances.

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

Stroke

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

Comparison

Three out of every 1,000 women, aged 50, who are not taking tibolona, may develop a stroke over a 5-year period. The number would be 7 out of every 1,000 women, aged 50, who are taking tibolona, and also over a 5-year period.

In women aged 60-69 who are not taking tibolona, it can be expected that 11 out of every 1,000 women will develop a stroke. In those taking tibolona, it would be 24 out of every 1,000 women who may develop a stroke.

Other Diseases

• 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 tibolona produces changes in cholesterol levels.
• Patients withheart failureorrenal failure:Estrogens can cause fluid retention,and thereforepatients with heart failureor renal failure should be carefully monitored.
• Patients withhypertriglyceridemia:Women with pre-existing hypertriglyceridemia should be closely monitored during treatment with tibolona,as there have been reports of rare cases of significant increases in plasma triglycerides, leading to pancreatitiswith estrogen therapy in this condition.

Other Medications and Tibolona Aristo

Some medications can alter the effects of tibolona and cause irregular bleeding. The following medications can cause this effect:

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

HRT can affect how other medications work:

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

Theconcomitant usewithtibolonamay increase the effect of anticoagulants(medicationsagainstblood clotting).

Theconcomitant usewithtibolonamay have an influence onmedications with active substances(e.g., midazolam)that are metabolized by certain enzymes(the so-calledcytochrome-P450 enzymes).

Inform your doctor or pharmacist if you are taking,have takenrecentlyor may need to take any other medication, including over-the-counter medications, medications from plants, or other natural products.

Your doctor will advise you.

Clinical Trials

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

Pregnancy and Breastfeeding

Do not take tibolona if you are pregnant or breastfeeding.

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

Driving and Using Machines

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

Tibolona Aristo Contains Lactose Monohydrate

If your doctor has told you that you are intolerant to certain sugars, consult with them before taking this medication.

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

How much Tibolona Aristo should be taken and for how long

Your doctor will prescribe the lowest possible dose to treat your symptoms for the shortest time possible. 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 per day after a meal, preferably at the same time every day.

Do not take a progestin preparation in addition to tibolona.

How to take Tibolona Aristo

Take the tablets with a little water or other 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 your ovaries have been surgically removed, 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 to rule out any malignant disease.

If you want to change to tibolona and previously took a medication with estrogens and progestins, please consult your doctor what to consider.

How long you should take Tibolona Aristo

Your doctor will aim to make the treatment as short as possible.

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

If you take more Tibolona Aristo than you should

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

It is unlikely that symptoms of intoxication will occur although several tablets are ingested at the same time. In case of acute overdose, nausea, vomiting, and intermenstrual bleeding may occur. 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 forgot 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 forgotten tablet and take the next tablet at the usual time.

Do not take a double dose to compensate for the missed doses.

If you need surgery

If you are going to undergo surgery, tell the surgeon that you are taking tibolona.It may be necessary to stop taking tibolona between 4 and 6 weeks before surgery to reduce the risk of a blood clot (see section 2, "Blood clots in 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.

The following diseases occur more frequently in women who follow THS (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
• Clots in the veins of the legs or lungs (venous thromboembolism)
• Heart disease
• Stroke
• Probable memory loss if THS started at an age above 65 years.

For more information on adverse effects, see section 2 “What you need to know before starting to take Tibolona Aristo”

Like all medicines, tibolona can cause adverse effects, although not all people will experience them.

Consult your doctor or pharmacistif you are concerned about any of the adverse 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 secretion, 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 (vulvovaginitis)
• Anomalies in the cervical smear

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

• Acne
• Breast or nipple pain
• Fungal infections

Other side effects reported for 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
• Joint or muscle pain
• Changes in liver function test results

Cases ofuterine lining cancer, breast cancer andstrokehave been reported in women taking tibolona (see section 2 “Warnings and precautions”).

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

•Bile duct disease

•Skin disorders:

• Discoloration of the skin, especially on the face and neck, known as “pregnancy mask” (melasma)
• Painful red nodules on the skin (erythema nodosum)
• Rash with redness or ulcers (erythema multiforme)
• Bleeding under the skin(purpuravascular)

Talk to your doctorif you have irregular vaginal bleeding or spottingor if you haveone of the side effects mentioned aboveorif they worsen.

Reporting of adverse effects

If you experienceany type of adverse effect, consult your doctor or pharmacist, even if it is a possibleadverse effect that does not appear in this prospectus.You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use:www.notificaram.es.By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

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.

No special storage conditions are required.

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

Medications should not be disposed of through drains or in the trash.Deposit the packaging and medications you no longer need at the SIGREpoint of the pharmacy. Please ask your pharmacist how to dispose ofthe packaging and medications you no longerneed.This will help protect the environment.

Composition of Tibolona Aristo

• The active principle is Tibolona.

Each tablet contains 2.5 mg of tibolona.

• The other components are:

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

Appearance of the product and content of the packaging

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

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

Not all packaging may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Aristo Pharma GmbH

Wallenroder Str. 8-10

13435 Berlin, Germany

Responsible for manufacturing

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

Last review date of this leaflet:November 2023.

The detailed information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.es/