ELTROMBOPAG ZENTIVA 25 mg FILM-COATED TABLETS

2. What you need to know before you take Eltrombopag Zentiva

Do not takeEltrombopag Zentiva

• if you are allergic to eltrombopag or any of the other ingredients of this medicine (listed in section 6),

Talk to your doctor if you think this may apply to you.

Warnings and precautions

Talk to your doctor or pharmacist before you start taking eltrombopag:

• if you have liver problems. People who have low platelet counts and advanced chronic liver disease are at a higher risk of side effects, including potentially life-threatening liver damage and blood clots. If your doctor thinks that the benefits of taking this medicine outweigh the risks, you will be closely monitored during treatment.
• if you are at risk of getting a blood clot in your veins or arteries, or if you know that blood clots are a common problem in your family.

The risk of getting a blood clot may be higher in the following situations:

• if you are older
• if you have been bedridden for a long time
• if you have cancer
• if you are taking the contraceptive pill or hormone replacement therapy
• if you have recently had surgery or have been physically injured
• if you are very overweight (obese)
• if you smoke
• if you have advanced chronic liver disease.

If any of these apply to you, tell your doctor before you start treatment. You must not take eltrombopag unless your doctor thinks that the expected benefit is greater than the risk of blood clots.

• if you have cataracts (the lens in the eye becomes cloudy)
• if you have another blood disorder, such as myelodysplastic syndrome (MDS). Your doctor will do tests to check that you do not have this blood disorder before you start taking eltrombopag. If you have MDS and take this medicine, your MDS may get worse.

Tell your doctor if any of these situations apply to you.

Eye examinations

Your doctor will recommend that you have an eye examination to check for cataracts. If you do not have regular eye checks, your doctor may arrange for you to have regular checks. You may also be checked for any bleeding in or around the retina (the layer of light-sensitive cells at the back of the eye).

You will need to have regular blood tests

Before you start taking eltrombopag, your doctor will do blood tests to check your blood cells, including your platelets. These tests will be repeated frequently while you are taking the medicine.

Blood tests to check your liver

Eltrombopag may cause changes in your blood test results that can be signs of liver damage: an increase in some liver enzymes, especially bilirubin and alanine/aspartate transaminases. If you are taking interferon-based treatments with eltrombopag to treat low platelet counts due to hepatitis C, some of your liver problems may get worse.

You will have blood tests to check your liver before you start taking eltrombopag and frequently while you are taking it. You may need to stop taking eltrombopag if the levels of these markers increase too much or if you get other signs of liver damage.

Read the information on “Liver problems” in section 4 of this leaflet.

Blood tests to check your platelet count

If you stop taking eltrombopag, it is likely that your platelet count will fall back to its previous level within a few days. Your platelet levels will be checked and your doctor will tell you what precautions to take.

Very high platelet counts can increase the risk of blood clots. However, blood clots can also occur with normal or even low platelet counts. Your doctor will adjust your dose of eltrombopag to make sure that your platelet count does not get too high.

Seek medical help immediately if you get any of the following signs of a blood clot:

• swelling, pain, or tenderness in one leg
• sudden difficulty breathing, especially if this is with sharp chest pain or rapid breathing
• abdominal (stomach) pain, a swollen abdomen, blood in your stools.

Tests to examine your bone marrow

In people who have problems with their bone marrow, medicines like eltrombopag may make these problems worse. Signs of changes in the bone marrow may appear as abnormal blood test results. Your doctor may also do tests to directly check your bone marrow while you are taking eltrombopag.

Checking for bleeding in the gut

If you are taking interferon-based treatments with eltrombopag, you will be monitored for any signs of bleeding in the stomach or intestines after you stop taking this medicine.

Heart monitoring

Your doctor may consider it necessary to monitor your heart while you are taking eltrombopag and may do an electrocardiogram (ECG) test.

Elderly (65 years and over)

There is limited information on the use of eltrombopag in patients aged 65 years and over. Caution should be used when taking eltrombopag if you are 65 years or older.

Children and adolescents

Eltrombopag is not recommended for children under 1 year of age with ITP. It is also not recommended for children under 18 years of age with low platelet counts due to hepatitis C.

Other medicines and Eltrombopag Zentiva

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines that you buy without a prescription and herbal medicines.

Some common medicines may interact with eltrombopag, including prescription and non-prescription medicines and minerals. These include:

• antacids for indigestion, heartburn, or stomach ulcers (see also “When to take it” in section 3)
• statins to lower cholesterol
• certain medicines to treat HIV infection, such as lopinavir and/or ritonavir
• ciclosporin used in transplants or immune system diseases
• minerals such as iron, calcium, magnesium, aluminium, selenium, and zinc that may be found in vitamin and mineral supplements (see also “When to take it” in section 3)
• medicines such as methotrexate and topotecan to treat cancer.

Talk to your doctor if you are taking any of these medicines. Some of them must not be taken with eltrombopag, or it may be necessary to adjust the dose or the time at which you take them. Your doctor will review the medicines that you are taking and suggest alternative medicines if necessary.

If you are also taking medicines to prevent blood clots, there is a higher risk of bleeding. Your doctor will discuss this with you.

If you are taking corticosteroids, danazol, and/or azathioprine, you may need to take a lower dose or stop taking them while you are taking eltrombopag.

Taking Eltrombopag Zentiva with food and drink

Do not take eltrombopag with dairy foods or drinks, as the calcium in these foods affects the absorption of the medicine. For more information, see “When to take it” in section 3.

Pregnancy and breastfeeding

Do not take eltrombopag if you are pregnant unless your doctor specifically recommends it. The effects of eltrombopag during pregnancy are not known.

• Tell your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant.
• Use a reliable method of contraception while you are taking eltrombopag to prevent pregnancy.
• If you become pregnant while taking eltrombopag, tell your doctor.

Do not breastfeed while you are taking eltrombopag. It is not known if eltrombopag passes into breast milk.

If you are breastfeeding or plan to breastfeed, talk to your doctor.

Driving and using machines

Eltrombopag may cause dizziness and have other effects that may make you less alert.

Do not drive or use machines unless you are sure that eltrombopag does not affect you.

Eltrombopag Zentiva contains isomalt and sodium

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

This medicine contains less than 1 mmol sodium (23 mg) per tablet, which is essentially “sodium-free”.

3. How to take Eltrombopag Zentiva

Take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist. Do not change the dose or stop taking eltrombopag unless your doctor or pharmacist tells you to. While you are taking eltrombopag, you will be under the care of a specialist doctor who is experienced in treating your condition.

How much to take

For ITP

Adults and children (6 to 17 years): the usual starting dose for ITP is one 50 mg tablet of eltrombopag per day.

If you are of East or South-East Asian origin, you may need to start with a lower dose of 25 mg.

Children (1 to 5 years): the usual starting dose for ITP is one 25 mg tablet of eltrombopag per day.

For hepatitis C

Adults: the usual starting dose for hepatitis C is one 25 mg tablet of eltrombopag per day.

If you are of East or South-East Asian origin, you will start with the same dose of 25 mg.

Eltrombopag may take 1 to 2 weeks to start working. Depending on your response to eltrombopag, your doctor may recommend that you change your daily dose.

How to take the tablets

Swallow the tablet whole with a little water.

When to take it

Make sure that

• in the 4 hours before you take eltrombopag
• and in the 2 hours after you take eltrombopag

you do not eat or drink any of the following:

• dairy products such as cheese, butter, yogurt, or ice cream
• milk or milkshakes, drinks that contain milk, yogurt, or cream
• antacids, a type of medicine for indigestion and heartburn
• certain mineral and vitamin supplements, including iron, calcium, magnesium, aluminium, selenium, and zinc.

If you do, the medicine will not be absorbed properly into your body.

For more information about suitable foods and drinks, talk to your doctor.

If you take more Eltrombopag Zentiva than you should

Talk to your doctor or pharmacist immediately. If possible, show them the pack or this leaflet. You will be monitored for any signs or symptoms of side effects and will be given the appropriate treatment as soon as possible.

In case of overdose or accidental ingestion, talk to a doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, stating the medicine and the amount taken.

If you forget to take Eltrombopag Zentiva

Take your next dose at the usual time. Do not take more than one dose of eltrombopag in a day.

If you stop taking Eltrombopag Zentiva

Do not stop taking eltrombopag without talking to your doctor. If your doctor advises you to stop treatment, your platelet levels will be checked every week for four weeks. See also “Bleeding or bruising after stopping treatment” in section 4.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Symptoms that require attention: consult a doctor

People taking eltrombopag for ITP or for a low platelet count due to hepatitis C may develop signs related to potentially serious adverse effects. It is essential to inform a doctor if these symptoms occur.

Increased risk of thrombosis

Some people may have an increased risk of suffering from thrombosis, and medications like eltrombopag could worsen this problem. The sudden blockage of a blood vessel by a thrombus is a rare adverse effect and can affect up to 1 in 100 people.

Seek immediate medical attention if you experience signs and symptoms of a thrombus, such as:

• swelling, pain, heat, redness, or sensitivity in one leg
• sudden difficulty breathing, especially when accompanied by acute chest pain or rapid breathing
• abdominal pain (stomach), enlarged abdomen, blood in the stool.

Liver problems

Eltrombopag may cause changes that appear in blood tests and can be signs of liver damage. Liver problems (elevated enzymes in blood tests) are common and can affect up to 1 in 10 people.

Other liver problems are rare and can affect up to 1 in 100 people.

If you have any of these signs of liver problems:

• yellowing of the skin or the whites of the eyes (jaundice)
• unusually dark-colored urine

Inform your doctor immediately.

Bleeding or bruising after treatment interruption

Within two weeks after stopping eltrombopag, your platelet count in the blood will generally return to the level it was before starting eltrombopag. A decrease in platelet levels can increase the risk of bleeding or bruising. Your doctor will monitor your platelet levels for at least 4 weeks after stopping this medication.

Inform your doctor if you experience bleeding or bruising after stopping treatment with eltrombopag.

Some people experience bleeding in the digestive system after stopping peginterferon, ribavirin, and eltrombopag. The symptoms include:

• black, tarry stools (discolored stools are a rare adverse effect that can affect up to 1 in 100 people)
• blood in the stool
• vomiting blood or something that looks like coffee grounds

Inform your doctor immediately if you experience any of these symptoms.

The following adverse effects have been reported in association with eltrombopag treatment in adult patients with ITP:

Very common adverse effects(can affect more than 1 in 10 people)

• infection of the nose, sinuses, throat, and upper respiratory tract (upper respiratory tract infection)
• cough, common cold
• feeling of discomfort (nausea), diarrhea
• back pain

Very common adverse effectsthat may appear in blood tests:

• increase in liver enzymes (alanine aminotransferase (ALT))

Common adverse effects(can affect up to 1 in 10 people)

• flu (influenza), cold sores, pneumonia, irritation and inflammation (swelling) of the sinuses, inflammation (swelling) and infection of the tonsils, lung infection, sinus, nose, and throat infection, gum inflammation, sore throat, and discomfort when swallowing
• loss of appetite
• sleeping problems, depression
• decreased sensitivity in the skin, sensation of tingling, itching, or numbness, commonly called "tingling", sensation of drowsiness, migraine
• eye problems including abnormal eye tests, dry eye, eye pain, and blurred vision, decreased vision
• ear pain, sensation of spinning (vertigo)
• pain, swelling, and sensitivity in one of your legs (usually the calf) with hot skin in the affected area (signs of a blood clot in a deep vein), localized swelling filled with blood from a rupture in a blood vessel (hematoma), hot flashes
• runny nose
• mouth problems including dry mouth, mouth pain, sensitivity in the tongue, bleeding gums, mouth ulcers, toothache, vomiting, abdominal pain, digestive gases
• abnormal liver function
• skin changes including excessive sweating, itchy rash, red spots, changes in skin appearance, hair loss
• muscle pain, muscle spasm, muscle weakness, bone pain
• foamy or bubbly urine (signs of protein in the urine)
• heavy menstrual period
• high temperature, feeling of heat, chest pain, feeling of weakness

Common adverse effectsthat may appear in blood tests:

• decrease in the number of red blood cells (anemia), decrease in the number of platelets (thrombocytopenia), decrease in the number of white blood cells, decrease in hemoglobin levels, increase in the number of eosinophils, increase in the number of white blood cells (leukocytosis)
• increase in uric acid levels, decrease in potassium levels
• increase in liver enzymes (aspartate aminotransferase (AST)), increase in bilirubin in the blood (a substance produced by the liver)
• high levels of some proteins, high levels of creatinine
• increase in alkaline phosphatase levels

Uncommon adverse effects(can affect up to 1 in 100 people)

• skin infection
• rectal and colon cancer
• allergic reaction
• loss of appetite, pain and swelling of the joints caused by uric acid (gout)
• lack of interest, mood changes, uncontrollable crying or crying at unexpected times
• problems with balance, speech, and nerve function, tremors, paralysis on one side of the body, migraine with aura, nerve damage, dilation or swelling of blood vessels that cause headache
• eye problems including increased tear production, cloudy lens (cataracts), retinal bleeding, dry eyes
• rapid or irregular heartbeats, blue discoloration of the skin, heart rhythm disorders (prolonged QT interval) that could be signs of a heart and blood vessel disorder, interruption of blood supply to a part of the heart
• possible pain, swelling, and/or redness around a vein, which could be signs of a blood clot in a vein, blood clot, hot flashes
• sudden difficulty breathing, especially when accompanied by acute chest pain and/or rapid breathing, which could be signs of a blood clot in the lungs (see "Increased risk of thrombosis" earlier in section 4), loss of function of part of the lung due to a blockage in the pulmonary artery, problems with the nose, throat, and sinuses, sleep breathing problems
• mouth problems, including dry mouth or irritation, tongue pain, gum bleeding, mouth discomfort, blisters/sores in the mouth and throat, digestive system problems including frequent stools, food poisoning, blood in the stool, vomiting blood, rectal bleeding, changes in stool color, abdominal distension, constipation
• yellowing of the skin and/or abdominal pain that could be signs of a blockage in the biliary tract, liver injury, liver damage due to inflammation (see "Liver problems" earlier in section 4), liver damage due to medication
• pain or abnormal sensations in the skin, skin changes including discoloration, peeling, redness, itching, and sweating, cold sweats
• muscle weakness
• kidney problems, including kidney inflammation, excessive urination at night, kidney failure, white blood cells in the urine
• feeling of heat, anxiety, bleeding around a catheter (if present) in the skin, redness or inflammation around a wound, general discomfort, feeling of a foreign body
• sunburn

Uncommon adverse effectsthat may appear in laboratory tests:

• changes in the shape of red blood cells, decrease in the number of red blood cells (anemia) caused by excessive destruction of red blood cells (hemolytic anemia), increase in the number of myelocytes, increase in neutrophil bands, presence of immature white blood cells that may be indicative of certain diseases, increase in the number of platelets, increase in hemoglobin levels
• decrease in calcium levels
• increase in blood urea, increase in protein levels in the urine
• increase in albumin levels in the blood, increase in total protein levels, decrease in albumin levels in the blood, increase in urine pH

The following additional adverse effects have been reported in association with eltrombopag treatment in children (1 to 17 years) with ITP:

If these adverse effects become severe, inform your doctor, pharmacist, or nurse.

Very common adverse effects(can affect more than 1 in 10 children)

• infection of the nose, sinuses, throat, and upper respiratory tract, common cold (upper respiratory tract infection)
• cough
• feeling of discomfort (nausea), diarrhea, abdominal pain
• high temperature

Common adverse effects(can affect up to 1 in 10 children)

• difficulty sleeping (insomnia)
• itching, nasal discharge, or congestion, throat irritation, runny nose, nasal congestion, and sneezing, throat pain
• toothache, mouth problems including dryness, irritation in the mouth, sensitivity in the tongue, gum bleeding, mouth ulcers

The following adverse effects have been reported in association with eltrombopag treatment in combination with peginterferon and ribavirin in patients with HCV:

Very common adverse effects(can affect more than 1 in 10 people)

• loss of appetite
• headache
• cough
• feeling of discomfort (nausea), diarrhea
• itching, swelling in the hands or feet, unusual hair loss
• muscle pain, muscle weakness
• fever, feeling of fatigue, flu-like symptoms, feeling of weakness, chills

Very common adverse effectsthat may appear in blood tests:

• decrease in the number of red blood cells (anemia)

Common adverse effects(can affect up to 1 in 10 people)

• urinary tract infection, infection of the nose, sinuses, throat, and upper respiratory tract, common cold (upper respiratory tract infection), inflammation of the mucous membrane that lines the bronchi, inflammation of the sinuses, throat, and mouth, flu-like symptoms, dry mouth, painful or inflamed mouth, toothache, flu (influenza), cold sores
• weight loss
• sleep disorders, excessive sleepiness, depression, anxiety
• dizziness, attention and memory problems, mood changes, decreased brain function due to liver damage, tingling or numbness in the hands or feet
• eye problems, including cataracts, dry eyes, small yellow deposits in the retina, yellowing of the white part of the eye, retinal bleeding
• feeling of spinning (vertigo)
• rapid or irregular heartbeats (palpitations)
• difficulty breathing, cough with phlegm, runny nose, throat irritation, and discomfort when swallowing
• digestive system problems, including vomiting, stomach pain, indigestion, constipation, stomach swelling, taste disturbances, hemorrhoids, stomach pain/discomfort, esophageal inflammation and bleeding, toothache
• liver problems, including liver tumors, yellowing of the white part of the eyes or skin (jaundice), liver injury due to medication (see "Liver problems" earlier in section 4)
• skin changes, including rash, dry skin, eczema, skin redness, itching, excessive sweating, unusual skin growths, hair loss
• joint pain, back pain, bone pain, pain in the limbs (arms, legs, hands, or feet), muscle spasms
• irritability, general discomfort, skin reactions such as redness or swelling and pain at the injection site, chest pain and discomfort, fluid retention in the body or limbs that causes swelling
• depression, anxiety, sleep problems, nervousness
• fever, headache

Common adverse effectsthat may appear in blood tests:

• increase in blood sugar (glucose), decrease in the number of white blood cells, decrease in the number of neutrophils, decrease in albumin levels in the blood, decrease in hemoglobin levels, increase in bilirubin levels in the blood (a substance produced by the liver), changes in the enzymes that control blood clotting

Uncommon adverse effects(can affect up to 1 in 100 people)

• stomach flu (gastroenteritis), sore throat
• decrease in the number of red blood cells (anemia) caused by excessive destruction of red blood cells (hemolytic anemia)
• confusion, agitation
• blistering/sores in the mouth, stomach inflammation
• blood clots in a vein that goes to the liver (possible liver and/or digestive system damage), liver failure
• skin changes, including color changes, peeling, redness, itching, and lesions, and night sweats
• abnormal blood clotting in small blood vessels with kidney failure, painful urination
• rash, bruising at the injection site, chest discomfort
• heart rhythm disorders (prolonged QT interval)

The following adverse effects have been reported in association with eltrombopag treatment in patients with severe aplastic anemia (SAA):

If these adverse effects become severe, inform your doctor, pharmacist, or nurse.

Very common adverse effects(can affect more than 1 in 10 people)

• headache, dizziness
• cough, mouth and throat pain
• diarrhea, feeling of discomfort (nausea), gum bleeding, abdominal pain
• joint pain (arthralgia), pain in the limbs (arms, legs, hands, and feet), muscle spasms
• feeling of extreme fatigue, fever, chills
• eye itching
• mouth blisters

Very common adverse effectsthat may appear in blood tests:

• abnormal changes in bone marrow cells
• increase in liver enzymes (aspartate aminotransferase (AST))

Common adverse effects(can affect up to 1 in 10 people)

• interruption of blood supply to the spleen (splenic infarction)
• anxiety, depression
• fainting
• eye problems, including vision problems, blurred vision, cataracts, floaters (vitreous floaters), dry eyes, eye itching, yellowing of the white part of the eyes or skin
• nosebleeds, runny nose
• digestive system problems, including difficulty swallowing, mouth pain, swollen tongue, vomiting, loss of appetite, stomach pain/discomfort, stomach swelling, gas, constipation, intestinal motility disorder that can cause constipation, bloating, diarrhea, and/or the mentioned symptoms, change in stool color
• skin problems, including small red or purple spots caused by bleeding in the skin (petechiae), rash, itching, hives, skin lesions
• back pain, muscle pain, bone pain
• abnormal urine color
• weakness (asthenia), swelling of the lower limbs due to fluid accumulation, general discomfort, feeling of cold

Common adverse effectsthat may appear in blood tests:

• decrease in white blood cell levels
• iron accumulation in the body (iron overload), decrease in blood sugar levels (hypoglycemia)
• increase in bilirubin levels in the blood (a substance produced by the liver)
• increase in enzymes due to muscle breakdown (creatine phosphokinase)

Adverse effects of unknown frequency(frequency cannot be estimated from available data)

• liver damage due to medication
• skin discoloration, skin darkening

Reporting adverse effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Eltrombopag Zentiva

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

Do not use this medicine after the expiry date which is stated on the blister and on the carton after "EXP". The expiry date refers to the last day of the month shown.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help to protect the environment.

6. Package contents and additional information

Composition ofEltrombopag Zentiva

• The active substance is eltrombopag olamine.

Eltrombopag Zentiva 25 mg: Each film-coated tablet contains eltrombopag olamine equivalent to 25 mg of eltrombopag.

Eltrombopag Zentiva 50 mg: Each film-coated tablet contains eltrombopag olamine equivalent to 50 mg of eltrombopag.

• The other ingredients are: microcrystalline cellulose, mannitol, povidone, isomalt (E 953), calcium silicate, sodium carboxymethyl starch, magnesium stearate (tablet core); hypromellose, titanium dioxide (E171), red iron oxide (E 172), triacetin (tablet coating).

• The film-coated tablets of Eltrombopag Zentiva 25 mg and 50 mg also contain yellow iron oxide (E172).

Appearance and package contents

Eltrombopag Zentiva 25 mg are film-coated tablets (tablets) biconvex, round, dark pink, with "II" engraved on one side and with a diameter of approximately 8 mm.

Eltrombopag Zentiva 50 mg are film-coated tablets (tablets) biconvex, round, pink, with "III" engraved on one side and with a diameter of approximately 10 mm.

Eltrombopag Zentiva 25 mg and 50 mg is available in boxes containing 14, 28 or 84 film-coated tablets in blisters, or in boxes containing 14x1, 28x1 or 84x1 film-coated tablets in unit-dose blisters.

Only certain pack sizes may be marketed.

Marketing authorisation holder and manufacturer

Marketing authorisation holder

Zentiva, k.s.

U Kabelovny 130

Dolní Mecholupy,

102 37 Prague 10

Czech Republic

Manufacturer

Synthon B.V.

Microweg 22

6545 CM Nijmegen

Netherlands

Or

Synthon Hispania S.L.

c/ Castelló, 1

08830 Sant Boi de Llobregat

Barcelona

Spain

You can request more information about this medicine from the local representative of the marketing authorisation holder:

Zentiva Spain S.L.U.

Avenida de Europa, 19, Edificio 3, Planta 1.

28224 Pozuelo de Alarcón, Madrid

Spain

This medicine is authorised in the Member States of the European Economic Area under the following names:

Date of last revision of this leaflet: May 2024

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