TILIA 2.5 mg TABLETS

Introduction

Package Leaflet: Information for the Patient

Tilia 2.5 mg EFG Tablets

tibolone

Read the entire package leaflet carefully before starting to take this medication, as it contains important information for you.

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

Contents of the Package Leaflet

1. What is Tilia and what is it used for
2. What you need to know before taking Tilia
3. How to take Tilia
4. Possible side effects
5. Storage of Tilia
6. Package contents and additional information

1. What is Tilia and what is it used for

The active substance is tibolone.

Tilia is a Hormone Replacement Therapy (HRT). Tilia is used in postmenopausal women who have had their last natural menstrual period at least 12 months ago.

Tilia is used to:

Relieve symptoms that occur after menopause.

During menopause, the amount of estrogen produced by the body decreases. This can cause symptoms such as a feeling of heat in the face, neck, and chest ("hot flashes"). Tilia relieves these symptoms after menopause. Tilia will only be prescribed if your symptoms are seriously affecting your daily activities.

2. What you need to know before taking Tilia

Follow your doctor's instructions carefully.

Medical history and regular medical check-ups

The use of HRT or Tilia involves risks that need to be considered when deciding whether to start treatment or continue taking it. This is especially important if you are over 60 years old.

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

Before starting (or restarting) HRT or Tilia

Your doctor will ask about your medical history and that of your family. Your doctor may decide to perform a physical examination, which may include a breast examination and/or internal examination, if necessary.

Regular medical check-ups

Once you have started taking Tilia, you should see your doctor for regular check-ups (at least once a year). During these check-ups, discuss the benefits and risks of continuing Tilia with your doctor.

Have regular mammograms as recommended by your doctor.

Do not take Tilia

Do not take Tilia if you have any of the following conditions. If you are unsure about any of them, consult your doctorbefore taking this medication:

• if you are allergic to tiboloneor any of the other ingredients of this medication (listed in section 6);
• if you have or have had breast cancer, or if you suspect you may have it;
• if you have an estrogen-sensitive cancer, such as cancer of the tissue lining the uterus (endometrium), or if it is suspected that you may have it;
• if you are pregnantor suspect you may be pregnant;
• if you are breastfeeding;
• if you have any unexplained vaginal bleeding;
• if you have excessive growth of the tissue lining the uterus(endometrial hyperplasia) that is not being treated;
• if you have or have had a blood clot in a vein(thrombosis), in the legs (deep vein thrombosis) or lungs (pulmonary embolism);
• if you have a blood clotting disorder(such as protein C deficiency, protein S deficiency, or antithrombin deficiency);
• if you have or have recently had a disease caused by blood clots in the arteries, such as heart attack, stroke, or angina;
• if you have or have had a liver diseaseand your liver function tests have not returned to normal;
• if you have a rare blood disorder called "porphyria" that is inherited.

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

If you have just started menopause, you should not take Tilia until 12 months after your last natural menstrual period. If you start treatment before this, you may experience irregular bleeding.

Warnings and precautions

Consult your doctor before starting Tilia.

Before starting treatment, inform your doctor if you have had any of the following problems, as they may recur or worsen during treatment with Tilia. If so, you should see your doctor more frequently for medical check-ups:

• fibroids in the uterus;
• growth of the tissue lining the uterus (endometriosis) or a history of excessive growth of the tissue lining the uterus (endometrial hyperplasia);
• increased risk of developing blood clots (see "Blood clots in a vein (thrombosis)");
• increased risk of developing an estrogen-sensitive cancer (e.g., if your mother, sister, or grandmother had breast cancer);
• high blood pressure;
• a liver disorder, such as a benign liver tumor;
• diabetes;
• gallstones;
• migraines or severe headaches;
• a disease of the immune system that affects many organs of the body (systemic lupus erythematosus, SLE);
• epilepsy;
• asthma;
• a disease that affects the eardrum and hearing (otosclerosis);
• very high levels of fat in your blood (triglycerides);
• fluid retention due to heart or kidney problems.

Stop taking Tilia and see a doctor immediately

If you experience any of the following symptoms while taking HRT or Tilia:

• any of the conditions mentioned in the section "Do not take Tilia";
• yellowing of the skin or whites of the eyes (jaundice), which can be a sign of liver disease;
• a significant increase in blood pressure (symptoms may include headache, fatigue, dizziness).
• migraine-like headaches that appear for the first time;
• if you become pregnant;
• if you experience signs of a blood clot, such as:

• painful swelling and redness of the legs;
• sudden chest pain;
• difficulty breathing;

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

Note:Tilia is not a contraceptive. If you have had your last natural menstrual period less than 12 months ago or if you are under 50 years old, you may still need to use a contraceptive method to prevent pregnancy. Ask your doctor for advice.

HRT and Cancer

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

There are reports and studies that have recorded an increased growth of endometrial cells or cancer of the tissue lining the uterus in women treated with tibolone. This risk of endometrial cancer is higher the longer the treatment lasts.

Irregular bleeding

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

• continues beyond the first 6 months;
• starts when you have been taking Tilia for more than 6 months;
• continues after you have stopped taking Tilia;

→consult your doctor as soon as possible.

Breast cancer

Existing data show that the use of tibolone increases the risk of breast cancer. The additional risk depends on the duration of tibolone use. 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 are no data on the persistence of risk after stopping tibolone, but a similar pattern cannot be ruled out.

Comparison

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

Check your breasts regularly. Consult your doctorif you notice any changes, such as:

• skin dimpling or puckering
• changes in the nipple
• visible or palpable lumps

Ovarian cancer

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

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

Comparison

With the use of Tilia, the increased 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 blood clots in the veinsis approximately 1.3 to 3 times higher in women taking HRT than in those not taking it, especially during the first year of treatment.

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

The likelihood of a blood clot in the veins increases with age and if any of the following conditions are met. Inform your doctor if you meet any of these conditions:

• you are pregnant or have recently given birth
• you use estrogens
• you are unable to walk for a long time due to a major surgery, injury, or illness (see also section 3, If you need to have surgery)
• you are significantly overweight (BMI >30 kg/m2)
• you have a blood clotting disorder that requires long-term treatment with a medicine to prevent blood clots
• if a close relative has had a blood clot in the leg, lung, or other organ
• you have systemic lupus erythematosus (SLE)
• you have cancer

In case of symptoms of a blood clot, see "Stop taking Tilia and see a doctor immediately".

Comparison

On average, over a 5-year period, it can be expected that out of 1,000 women in their 50s who do not take HRT, 4 to 7 will have a blood clot in a vein.

While, out of 1,000 women of this age who have been taking HRT with estrogen and progestogen for more than 5 years, there will be 9 to 12 cases (i.e., 5 additional cases).

With the use of Tilia, the increased risk of developing a blood clot in a vein is lower than with other types of HRT.

Heart disease (heart attack)

There is no evidence that hormone replacement therapy (HRT) or Tilia prevents a heart attack.

Women over 60 years old who use combined estrogen and progestogen therapy are slightly more likely to have a heart attack than those who do not take it.

Stroke

Recent studies suggest that HRT and tibolone increase the risk of stroke. This increased risk has been observed mainly in women over 60 years old.

Comparison

On average, over a 5-year period, it can be expected that out of 1,000 women in their 50s who do not take tibolone, 3 will have a stroke, while for women of this age who take tibolone, the figure may be 7 out of 1,000 (i.e., 4 additional cases).

On average, over a 5-year period, it can be expected that out of 1,000 women in their 60s who do not take tibolone, 11 will have a stroke, while for women of this age who take tibolone, the figure may be 24 out of 1,000 (i.e., 13 additional cases).

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. Ask your doctor for advice.

Tilia is not indicated for use as a contraceptive.

Other medications and Tilia

Tell your doctor or pharmacist if you are taking, have recently taken, or may take any other medication, including non-prescription medications, herbal remedies, or other natural products.

Some medications may interfere with the effect of Tilia, which could lead to irregular bleeding. This occurs with the following medications:

• medications that prevent blood clotting(such as warfarin)
• medications for epilepsy(such as phenobarbital, phenytoin, and carbamazepine)
• medications for HIV infection(such as nevirapine, efavirenz, ritonavir, and nelfinavir)
• medications for tuberculosis(such as rifampicin)
• herbal remedies that contain St. John's Wort(Hypericum perforatum)

Tilia may alter the effects of certain medications, such as midazolam.

Clinical tests

If you are going to have a blood test, inform your doctor and the laboratory staff that you are taking Tilia, as this medication may alter the results of some tests.

Pregnancy, breastfeeding, and fertility

Tilia is indicated only for postmenopausal women. If you become pregnant, stop taking Tilia and contact your doctor.

Driving and using machines

No adverse effects of Tilia on the ability to drive or use machines have been reported.

Tilia contains lactose

If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

If you are concerned about anything in this section, talk to your doctor about the risks and benefits of hormone replacement therapy (HRT).

3. How to take Tilia

Follow your doctor's instructions for taking this medication exactly. If you are unsure, consult your doctor or pharmacist.

How much Tilia to take and for how long

Unless your doctor has prescribed a different dose, the usual dose is:

one tablet a day after a meal, preferably at the same time each day.

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.

Do not take a progestogen preparation with Tilia.

How to take Tilia

Take the tablets with a little water or other drink, without chewing, preferably at the same time each day.

What to consider when starting treatment with Tilia

• If you have had a natural menopause, you should start taking Tilia at least 1 year after your last natural menstrual period. If you have had your ovaries removed by surgery, you can start taking Tilia immediately.
• If you want to start taking Tilia and have experienced irregular or unexpected vaginal bleeding, please contact the doctor treating you before starting treatment with Tilia to rule out any malignant disease.
• If you want to switch from Tilia to another medication that contains an estrogen and a progestogen, please consult your doctor to find out what you need to consider.

If you need to have surgery

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

If you feel that the effect of Tilia is too strong or too weak, consult your doctor or pharmacist.

If you take more Tilia than you should

If you have taken more Tilia than you should, consult a doctor or pharmacist immediately.

It is unlikely that you will experience symptoms of overdose, even if you take several tablets at the same time. In case of acute overdose, nausea, vomiting, and intermenstrual bleeding may occur. If necessary, consult your doctor to 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 taken.

If you forget to take Tilia

If you forget to take a tablet at the 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 make up for forgotten doses.

If you are unsure about the use of Tilia, consult your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. Most of these adverse effects are mild.

The following diseases have been reported more frequently in women undergoing THS treatment than in those not undergoing treatment:

• breast cancer
• abnormal growth or cancer of the tissue lining the inside of the uterus (endometrial hyperplasia or endometrial cancer)
• ovarian cancer
• blood clots in the veins of the legs or lungs (venous thromboembolism)
• heart disease
• stroke
• probable memory loss if THS is started after the age of 65.

For more information on adverse effects, see section 2.

Consult your doctor or pharmacistif you are concerned about any adverse effects that you think may be caused by Tilia, also see section 2 "Stop taking Tilia and go to the doctor immediately"

Severe adverse effects – consult your doctor immediately

If you think you are experiencing symptoms of a severe adverse effect, go to your doctor immediately.

You may need to stop taking Tilia:

• if your blood pressure increases;
• if your skin or the whites of your eyes turn yellow (jaundice);
• if you suddenly have migraines (see section 2 above);
• if you have symptoms of a blood clot (see section 2 above);
• if you have any of the problems listed in section 2 ("Do not take Tilia")

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 concern in the first few months of starting THS treatment. If bleeding continues or starts after a period of time on THS, see Section 2.

• vaginal problems such as increased discharge, itching, irritation, and candidiasis
• growth of the lining of the uterus
• weight gain

Infrequent:may affect up to 1 in 100 women

• swelling of the hands, feet, and ankles, a sign of fluid retention
• stomach upset
• acne
• nipple pain or discomfort in the breasts
• vaginal infections

Rare:may affect up to 1 in 1,000 women

• skin itching

Some women using Tilia have also reported:

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

Cases of breast cancer as well as increased cell size or cancer of the lining of the uterus have been reported in women undergoing Tilia treatment.

The following adverse effects have been reported with other THSs:

• bile duct disorders
• skin disorders:
  • skin discoloration, especially on the face or neck, called "pregnancy spots" (chloasma)
  • red and painful skin nodules (erythema nodosum)
  • rash with redness or ulcers (erythema multiforme)
  • pinpoint bleeding on the skin (vascular purpura)

Tell your doctor if you experience vaginal bleeding or spotting, or if any of the adverse effects continue or become a problem.

Adverse Effect Reporting

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

5. Storage of Tilia

Keep this medicine out of the sight and reach of children.

.

Do not use this medicine after the expiration date shown on the packaging after "CAD". The expiration date is the last day of the month indicated.

Do not use this medicine if you notice that the blister is damaged or a blister is missing, even if the packaging is intact.

Medicines should not be thrown away through drains or into the trash. Deposit the packaging and medicines you no longer need at the SIGRE Point in the pharmacy. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

This medicine does not require special storage conditions

6. Package Contents and Additional Information

Tilia Composition

• The active ingredient is Tibolone. Each tablet contains 2.5 mg of tibolone.
• The other ingredients are potato starch, lactose monohydrate, magnesium stearate, and ascorbyl palmitate.

Product Appearance and Package Contents

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

Tilia is available in packages of 1 x 28 tablets and 3 x 28 tablets

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Aristo Pharma Iberia, S.L

C/ Solana, 26

28850, Torrejón de Ardoz

Madrid, Spain

Manufacturer

Aristo Pharma GmbH

Wallenroder Str. 8-10

D-13435 Berlin, Germany

Date of the last revision of this prospectus: August 2020

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