Bosutinib Zentiva

Leaflet attached to the packaging: information for the user

Bosutinib Zentiva, 100 mg, coated tablets

Bosutinib Zentiva, 400 mg, coated tablets

Bosutinib Zentiva, 500 mg, coated tablets

Bosutinib

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor. See section 4.

Table of contents of the leaflet

• 1. What is Bosutinib Zentiva and what is it used for
• 2. Important information before taking Bosutinib Zentiva
• 3. How to take Bosutinib Zentiva
• 4. Possible side effects
• 5. How to store Bosutinib Zentiva
• 6. Contents of the pack and other information

1. What is Bosutinib Zentiva and what is it used for

Bosutinib Zentiva contains the active substance bosutinib. This medicine is used to treat adult patients with a type of leukemia called chronic myeloid leukemia with Philadelphia chromosome positive (Ph-positive), who have been newly diagnosed or whose previous treatment for chronic myeloid leukemia has not worked or is not suitable. Chronic myeloid leukemia Ph-positive is a blood cancer that causes the body to produce too many specific white blood cells called granulocytes. If you have any questions about how Bosutinib Zentiva works or why it has been prescribed for you, you should ask your doctor.

2. Important information before taking Bosutinib Zentiva

When not to take Bosutinib Zentiva

• if you are allergic to bosutinib or any of the other ingredients of this medicine (listed in section 6)
• if you have been informed by your doctor that you have liver damage and it is not working properly.

Warnings and precautions

Before starting treatment with Bosutinib Zentiva, you should discuss it with your doctor, pharmacist, or nurse:

• if you have or have had liver disease in the past.You should tell your doctor about any previous liver disease, including hepatitis (infection or inflammation) of any type, as well as any previous signs and symptoms related to the liver, such as itching, yellowing of the whites of the eyes or skin, dark urine, and pain or discomfort in the right upper abdomen. Before starting treatment with Bosutinib Zentiva and during the first 3 months of treatment, and in clinically indicated situations, your doctor should perform blood tests to check your liver function.

You should tell your doctor if you experience any of the following signs and symptoms: increased daily number of stools (bowel movements) exceeding the normal amount, increased number of vomiting episodes, presence of blood in vomit, stools (bowel movements), or urine, presence of black stools (tar-like black bowel movements). You should ask your doctor if the use of anti-vomiting treatment may increase the risk of developing heart rhythm disturbances. You should consult your doctor especially if a medicine containing domperidone is to be used to treat nausea and/or vomiting. Treating nausea or vomiting with such medicines together with Bosutinib Zentiva may increase the risk of developing serious heart rhythm disturbances.

• if you have bleeding.You should tell your doctor if you experience any signs or symptoms, such as abnormal bleeding or bruising without injury.
• if you have an infection.You should tell your doctor if you experience any signs or symptoms, such as fever, problems urinating (e.g., burning), new cough, or sore throat.
• if you have fluid retention.You should tell your doctor if you experience any signs or symptoms of fluid retention, such as swelling of the ankles, feet, or legs, difficulty breathing, chest pain, or cough (which may be signs of fluid retention in the lungs or chest).
• if you have heart disease.You should tell your doctor if you have heart disease, such as heart failure and reduced blood flow to the heart, which may lead to a heart attack. If you experience shortness of breath, weight gain, chest pain, or swelling of the hands, ankles, or feet, you should seek medical attention immediately.
• if you have an abnormal heart rhythm.You should tell your doctor if you experience any arrhythmias or abnormal EKG signs called "QT interval prolongation". Such conditions are always significant, but are of particular importance in cases of frequent or prolonged diarrhea, as described above. If you experience fainting (loss of consciousness) or irregular heartbeat while taking Bosutinib Zentiva, you should contact your doctor immediately, as it may be a sign of a serious heart condition.
• if you have had kidney disease in the past.You should tell your doctor if you experience more frequent urination and production of a larger amount of pale urine, as well as less frequent urination and production of a smaller amount of dark urine. You should also tell your doctor if you experience weight loss and swelling of the feet, ankles, legs, hands, or face.
• if you have ever had or may currently have hepatitis B virus infection; this is because Bosutinib Zentiva may cause reactivation of hepatitis B virus infection, which may lead to death in some cases; patients will be closely monitored by their doctor for signs of this infection before starting treatment.
• if you have or have had pancreatitis.You should tell your doctor if you experience abdominal pain or discomfort in this area.
• if you experience any of the following symptoms: severe skin rash.

You should tell your doctor if you experience any of the following symptoms: painful, red, or purple spreading rash, blisters, and/or other lesions that start to appear on the mucous membranes (e.g., in the mouth and lips).

• if you notice any of the following symptoms: side pain, blood in the urine, or decreased urine output.In the case of a very severe disease, the body may not be able to remove all the components of dying cancer cells. This complication is called tumor lysis syndrome and may cause kidney failure and heart problems within 48 hours of administration of the first dose of Bosutinib Zentiva. Your doctor is aware of the possibility of this complication and may recommend that you be properly hydrated, as well as administer other medicines to prevent its occurrence.

Protection against sun/UV radiation

While taking bosutinib, you may be more sensitive to sunlight or UV radiation. It is essential to cover areas of skin exposed to sunlight and use sunscreens with a high sun protection factor (SPF).

Children and adolescents

Bosutinib Zentiva should not be used in people under 18 years of age. The use of this medicine has not been studied in children and adolescents.

Bosutinib Zentiva and other medicines

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take, including those available without a prescription, vitamins, and herbal medicines. Some medicines may affect the levels of Bosutinib Zentiva in your body. You should inform your doctor about taking medicines containing the following active substances:

The following active substances may increase the risk of side effects of Bosutinib Zentiva:

Bosutinib Zentiva:

• ketokonazole, itraconazole, voriconazole, posaconazole, and fluconazole used to treat fungal infections;
• clarithromycin, telithromycin, erythromycin, and ciprofloxacin used to treat bacterial infections;
• nefazodone used to treat depression;
• mibefradil, diltiazem, and verapamil used to lower blood pressure in people with high blood pressure;
• ritonavir, lopinavir/ritonavir, indinavir, nelfinavir, saquinavir, atazanavir, amprenavir, fosamprenavir, and darunavir used to treat human immunodeficiency virus (HIV)/AIDS;
• boceprevir and telaprevir used to treat hepatitis C;
• aprepitant used to prevent nausea (vomiting) and to control it;
• imatinib used to treat a type of leukemia;
• crizotinib used to treat a type of lung cancer called non-small cell lung cancer.

The following active substances may reduce the effectiveness of Bosutinib Zentiva:

• rifampicin used to treat tuberculosis;
• phenytoin and carbamazepine used to treat epilepsy;
• bosentan used to lower high blood pressure in the lungs (pulmonary arterial hypertension);
• nafcillin - an antibiotic used to treat bacterial infections;
• St. John's Wort (a herbal medicine available without a prescription) used to treat depression;
• efavirenz and etravirine used to treat HIV/AIDS infections;
• modafinil used to treat certain types of sleep disorders.

You should avoid taking these medicines while being treated with Bosutinib Zentiva. You should tell your doctor if you are taking any of these medicines. Your doctor may change the dose of these medicines, the dose of Bosutinib Zentiva, or change the medicine to another one.

The following active substances may affect heart rhythm:

• amiodarone, disopyramide, procainamide, quinidine, and sotalol used to treat heart rhythm disorders;
• chloroquine and halofantrine used to treat malaria;
• antibiotics: clarithromycin and moxifloxacin used to treat bacterial infections;
• haloperidol used to treat psychotic disorders, such as schizophrenia;
• domperidone used to treat nausea and vomiting or to stimulate milk production;
• methadone used to treat pain.

You should be cautious when taking these medicines while being treated with Bosutinib Zentiva. You should tell your doctor if you are taking any of these medicines. Other medicines not listed above may also interact with Bosutinib Zentiva.

Taking Bosutinib Zentiva with food and drink

You should not take Bosutinib Zentiva with grapefruit or grapefruit juice, as it may increase the risk of side effects.

Pregnancy, breastfeeding, and fertility

Bosutinib Zentiva may harm the unborn child, so you should not take it during pregnancy unless it is necessary. If you are pregnant or think you may be pregnant, you should consult your doctor before taking Bosutinib Zentiva. Women taking Bosutinib Zentiva should use effective contraception during treatment and for at least one month after the last dose of the medicine. Vomiting and diarrhea may reduce the effectiveness of oral contraceptives. Due to the risk of reduced fertility in men, you should consider sperm preservation before starting treatment with Bosutinib Zentiva. If you are breastfeeding, you should tell your doctor. You should not breastfeed while taking Bosutinib Zentiva, as it may harm the baby.

Driving and using machines

If you experience dizziness, blurred vision, or an unusual feeling of tiredness, you should not drive or operate machinery until these effects have stopped.

Bosutinib Zentiva contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per 100 mg, 400 mg, or 500 mg tablet, which means it is essentially "sodium-free".

3. How to take Bosutinib Zentiva

This medicine should always be taken exactly as your doctor has told you. If you are unsure, you should ask your doctor or pharmacist. Bosutinib Zentiva will only be prescribed by a doctor who has experience in the use of medicines to treat leukemia.

Dose and method of administration

The recommended dose for patients with newly diagnosed chronic myeloid leukemia is 400 mg once daily. The recommended dose for patients whose previous treatment for chronic myeloid leukemia has not worked or is not suitable is 500 mg once daily. In patients with moderate or severe kidney disease, the doctor will reduce the dose by 100 mg per day in the case of moderate kidney disease and by an additional 100 mg per day in the case of severe kidney disease. The doctor may adjust the dose using 100 mg tablets, depending on the patient's condition, response to treatment, and/or the occurrence of possible side effects. The tablets should be taken once daily with food. Bosutinib Zentiva tablets should be swallowed whole with water.

Taking a higher dose of Bosutinib Zentiva than recommended

If you accidentally take too many Bosutinib Zentiva tablets or a higher dose than needed, you should immediately consult your doctor. If possible, you should show your doctor the packaging of the medicine or this leaflet. You may need medical attention.

Missing a dose of Bosutinib Zentiva

If it has been less than 12 hours since you missed a dose, you should take the recommended dose. If it has been more than 12 hours since you missed a dose, you should take the next dose at the usual time the next day. You should not take a double dose to make up for a missed tablet.

Stopping treatment with Bosutinib Zentiva

You should not stop taking Bosutinib Zentiva unless your doctor tells you to. If you are unable to take the medicine as directed by your doctor or if you think you no longer need it, you should contact your doctor immediately. If you have any further questions about the use of this medicine, you should ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Bosutinib Zentiva can cause side effects, although not everybody gets them. If you experience any of the following serious side effects, you should contact your doctor immediately (see also section 2 "Important information before taking Bosutinib Zentiva"): Blood disorders.You should immediately tell your doctor if you experience any of the following symptoms: bleeding, fever, or easy bruising (which may indicate a blood or lymphatic system disorder). Liver function disorders.You should immediately tell your doctor if you experience any of the following symptoms: itching, yellowing of the whites of the eyes or skin, dark urine, abdominal pain or discomfort in the right upper abdomen, or fever. Gastrointestinal disorders.You should tell your doctor if you experience stomach pain, heartburn, diarrhea, constipation, nausea, and vomiting. Heart problems.You should tell your doctor if you experience heart rhythm disturbances, such as heart failure, reduced blood flow to the heart, abnormal electrical signals called "QT interval prolongation", fainting (loss of consciousness), or irregular heartbeat while taking Bosutinib Zentiva. Reactivation of hepatitis B virus infection.Recurrence (reactivation) of hepatitis B virus infection (liver infection) in patients who have had the disease in the past. Severe skin reactions.You should immediately tell your doctor if you experience any of the following symptoms: painful, red, or purple spreading rash, blisters, and/or other lesions that start to appear on the mucous membranes (e.g., in the mouth and lips). Side effects associated with taking Bosutinib Zentiva may include:

Very common side effects (may affect more than 1 in 10 people):

• decreased number of platelets, red blood cells, and/or neutrophils (a type of white blood cell),
• diarrhea, vomiting, abdominal pain, nausea,
• fever, swelling of the hands, feet, or face, fatigue, weakness,
• respiratory tract infection,
• nasopharyngitis,
• changes in blood test results to check if Bosutinib Zentiva affects the liver and/or pancreas, kidneys,
• decreased appetite,
• joint pain, back pain,
• headache,
• skin rash, which may be itchy and/or generalized,
• cough,
• shortness of breath,
• feeling of imbalance (dizziness),
• fluid in the lungs (pleural effusion),
• itching.

Common side effects (may affect up to 1 in 10 people):

• low number of white blood cells (leukopenia),
• gastritis (stomach inflammation), stomach or intestinal bleeding,
• chest pain, pain,
• toxic liver damage, abnormal liver function, including liver function disorder,
• pneumonia (lung infection), flu, bronchitis,
• heart failure (when the heart does not pump blood as well as it should),
• heart rhythm disturbances that may lead to fainting, dizziness, and palpitations,
• high blood pressure,
• high potassium levels in the blood, low phosphate levels in the blood, excessive loss of body fluids (dehydration),
• muscle pain,
• taste disturbance,
• acute kidney failure, kidney failure, kidney function disorders,
• fluid around the heart (fluid in the pericardium),
• ringing in the ears,
• hives, acne,
• sensitivity to sunlight (UV radiation from the sun and other sources of light),
• allergic reaction,
• high blood pressure in the pulmonary arteries (pulmonary hypertension),
• acute pancreatitis,
• respiratory failure.

Uncommon side effects (may affect up to 1 in 100 people):

• fever associated with low white blood cell count (febrile neutropenia),
• liver damage,
• life-threatening allergic reaction (anaphylactic shock),
• abnormal fluid accumulation in the lungs (acute pulmonary edema),
• skin rashes,
• pericarditis (inflammation of the sac surrounding the heart),
• significant decrease in the number of granulocytes (a type of white blood cell),
• severe skin disorders (erythema multiforme),
• nausea, shortness of breath, irregular heartbeat, muscle spasms, seizures, cloudy urine, and fatigue associated with abnormal laboratory test results (high potassium, uric acid, and phosphate levels and low calcium levels in the blood), which may lead to kidney function disorders and acute kidney failure - tumor lysis syndrome.

Frequency not known (frequency cannot be estimated from the available data):

• severe skin disorders (Stevens-Johnson syndrome, toxic epidermal necrolysis) due to an allergic reaction, exfoliative rash,
• interstitial lung disease (conditions that cause scarring in the lungs): symptoms include cough, difficulty breathing, painful breathing.

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder or its local representative. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Bosutinib Zentiva

The medicine should be stored out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the blister and carton after "EXP". The expiry date refers to the last day of the month. There are no special storage instructions for this medicine. Do not use this medicine if you notice damage to the packaging or signs of tampering. Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Bosutinib Zentiva contains

• The active substance of the medicine is bosutinib. Bosutinib Zentiva coated tablets are available in different strengths. Bosutinib Zentiva, 100 mg: each coated tablet contains 100 mg of bosutinib. Bosutinib Zentiva, 400 mg: each coated tablet contains 400 mg of bosutinib. Bosutinib Zentiva, 500 mg: each coated tablet contains 500 mg of bosutinib.
• Other ingredients are: microcrystalline cellulose (E 460), sodium croscarmellose (E 468), silicon dioxide, magnesium stearate. The tablet coating contains polyvinyl alcohol (E 1203), macrogol, talc (E 553b), titanium dioxide (E 171), yellow iron oxide (E 172) for Bosutinib Zentiva 100 mg and 400 mg, red iron oxide (E 172) for Bosutinib Zentiva 400 mg and 500 mg.

Bosutinib Zentiva, 100 mg, coated tablets: yellow, oval (6 mm x 11 mm) biconvex, with "C18" engraved on one side. Bosutinib Zentiva 100 mg is available in blisters containing 28 or 112 coated tablets, in a cardboard box. Bosutinib Zentiva 100 mg is available in single-dose perforated blisters containing 28 x 1 or 112 x 1 coated tablets, in a cardboard box. Bosutinib Zentiva, 400 mg, coated tablets: orange, oval (9 mm x 17 mm) biconvex, with "C19" engraved on one side. Bosutinib Zentiva 400 mg is available in blisters containing 28 coated tablets, in a cardboard box. Bosutinib Zentiva 400 mg is available in single-dose perforated blisters containing 28 x 1 coated tablets, in a cardboard box. Bosutinib Zentiva, 500 mg, coated tablets: pink, oval (10 mm x 18 mm) biconvex, with "C20" engraved on one side. Bosutinib Zentiva 500 mg is available in blisters containing 28 coated tablets, in a cardboard box. Bosutinib Zentiva 500 mg is available in single-dose perforated blisters containing 28 x 1 coated tablets, in a cardboard box. Not all pack sizes may be marketed.

Marketing authorization holder

Zentiva, k.s., U kabelovny 130, Dolní Měcholupy, 102 37 Prague 10, Czech Republic

Manufacturer

Coripharma ehf, Reykjavíkurvegur 78, 220 Hafnarfjörður, Iceland

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

For further information, please contact your local representative of the marketing authorization holder:

Zentiva Polska Sp. z.o.o., ul. Bonifraterska 17, 00-203 Warsaw, Poland, phone: +48 22 375 92 00 Date of last revision of the leaflet:June 2025