Prospect: Information for the User

Bosutinib Zentiva 100 mg Film-Coated Tablets

Bosutinib Zentiva 400 mg Film-Coated Tablets

Bosutinib Zentiva 500 mg Film-Coated Tablets

Read this prospect carefully before starting to take this medicine, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, even if they are not listed in this prospect. See section 4.

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

2. What you need to know before starting to take Bosutinib Zentiva

3. How to take Bosutinib Zentiva

4. Possible adverse effects

5. Storage of Bosutinib Zentiva

6. Contents of the pack and additional information

Bosutinib Zentiva contains the active ingredient bosutinib. It is used to treat adult patients who have a type of leukemia called chronic myeloid leukemia (CML) with a positive Philadelphia chromosome (Ph-positive) who have recently been diagnosed or for whom previous medications to treat CML have not been effective or are not suitable. Ph-positive CML is a blood cancer that causes the body to produce an excessive amount of a specific type of white blood cells called granulocytes.

If you have any doubts about how bosutinib works or why you have been prescribed this medication, consult your doctor.

No use BosutinibZentiva

• If you are allergic to bosutinib or any of the other ingredients in this medication (listed in section 6),
• If your doctor has told you that you have a damaged liver and it does not function normally.

Warnings and Precautions

Consult your doctor, pharmacist, or nurse before starting to take bosutinib

• If you have, or have had in the past, liver problems. Inform your doctor if you have a history of liver problems, including any type of hepatitis (infection or inflammation of the liver), or a history of any of the following signs and symptoms of liver problems: itching, yellow eyes or skin, dark urine, and pain or discomfort in the upper right side of the stomach. Your doctor should perform blood tests to check your liver function before starting treatment with bosutinib and during the first 3 months of treatment with bosutinib, and as clinically indicated.
• If you have diarrhea and vomiting. Inform your doctor if you experience any of the following signs and symptoms: increased frequency of bowel movements, increased frequency of vomiting episodes, blood in the vomit, in the stools (bowel movements) or in the urine, or the appearance of black stools (tarry stools). Consult your doctor if the treatment for vomiting may lead to a higher risk of cardiac arrhythmias. In particular, consult your doctor if you want to use a medication containing domperidone for the treatment of nausea and/or vomiting. The treatment of nausea or vomiting with medications of this type, if used in combination with bosutinib, may cause a higher risk of life-threatening cardiac arrhythmias.
• If you have bleeding problems. Inform your doctor if you experience any of the following signs and symptoms, such as abnormal bleeding or petechiae without any injury.
• If you have an infection. Inform your doctor if you experience any of the following signs and symptoms, such as fever, urinary problems such as burning sensation while urinating, new-onset cough or sore throat.
• If you have fluid retention. Inform your doctor if you experience any of the following signs and symptoms of fluid retention during treatment with bosutinib, such as swelling of the ankles, feet, or legs; difficulty breathing, chest pain, or cough (all of which may be signs of fluid retention in the lungs or chest).
• If you have heart problems. Inform your doctor if you have any cardiac alteration, such as arrhythmias or an abnormal electrical signal called "prolongation of the QT interval". These problems are always important, but even more so if you have frequent or prolonged diarrhea as indicated above. If you faint (lose consciousness) or experience irregular heartbeats during treatment with bosutinib, inform your doctor immediately, as they may be signs of a serious heart disease.
• If you have been told that you have kidney problems. Inform your doctor if you urinate more frequently and produce larger amounts of clear urine, or if you urinate less frequently and produce smaller amounts of dark urine. Also inform your doctor if you lose weight or experience swelling of the feet, ankles, legs, hands, or face.
• If you have ever had or may have a hepatitis B virus infection. This is because bosutinib may cause the hepatitis B virus to become active again, which can be fatal in some cases. The doctor should carefully check for signs of this infection before starting treatment.
• If you have or have had in the past pancreas problems. Inform your doctor if you experience abdominal pain or discomfort.
• If you experience any of the following symptoms: severe skin rash. Inform your doctor if you experience any of the following signs and symptoms of painful red or purple rash that spreads and if blisters and/or other lesions appear on the mucous membrane (e.g., the mouth and lips).
• If you experience any of the following symptoms: side pain, blood in the urine, or decreased urine output. If your disease is very severe, your body may not be able to eliminate all the waste products of dying cancer cells. This is known as tumor lysis syndrome and can cause kidney failure and heart problems within 48 hours of the first dose of bosutinib. Your doctor will ensure that you are adequately hydrated and will give you other medications to help prevent it.

Sol/Protección UV

During treatment with bosutinib, you may be more sensitive to the sun or UV rays. It is essential to cover exposed body areas and use a high-factor sunscreen (SPF).

Children and Adolescents

Bosutinib is not recommended for children under 18 years of age. This medication has not been studied in children or adolescents.

Other Medications and Bosutinib Zentiva

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including over-the-counter medications, vitamins, and herbal supplements.

Some medications may affect the concentrations of bosutinib in your body. You should inform your doctor if you are using medications that contain active ingredients such as the following:

The following active ingredients may increase the risk of adverse effects with Bosutinib Zentiva:

• ketoconazole, 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 reduce blood pressure in people with high blood pressure.
• ritonavir, lopinavir/ritonavir, indinavir, nelfinavir, saquinavir, atazanavir, amprenavir, fosamprenavir, and darunavir, used to treat HIV/AIDS.
• boceprevir and telaprevir, used to treat hepatitis C.
• aprepitant, used to prevent and control nausea and vomiting.
• imatinib, used to treat a type of leukemia.
• crizotinib, used to treat a type of lung cancer called non-microcytic lung cancer.

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

• rifampicin, used to treat tuberculosis.
• phenytoin and carbamazepine, used to treat epilepsy.
• bosentan, used to reduce high blood pressure in the lungs (pulmonary hypertension).
• nafcillin, an antibiotic used to treat bacterial infections.
• St. John's Wort (a medicinal herb obtained without a prescription), used to treat depression.
• efavirenz and etravirine, used to treat HIV/AIDS.
• modafinil, used to treat certain types of sleep disorders.

You should avoid using these medications during treatment with bosutinib. If you are using any of them, inform your doctor. Your doctor may change the doses of these medications, change the dose of bosutinib, or have you use a different medication.

The following active ingredients may affect heart rate:

• amiodarone, disopyramide, procainamide, quinidine, and sotalol, used to treat cardiac arrhythmias.
• chloroquine and halofantrine, used to treat malaria.
• clarithromycin and moxifloxacin, which are antibiotics 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.

These medications should be taken with caution during treatment with bosutinib. If you are taking any of them, inform your doctor.

It is possible that the medications listed in this prospectus may not be the only ones that could interact with bosutinib.

Taking Bosutinib Zentiva with food and drinks

Do not take bosutinib with grapefruit or grapefruit juice, as it may increase the risk of adverse effects.

Pregnancy, breastfeeding, and fertility

Bosutinib should not be used during pregnancy unless it is clearly necessary, as bosutinib may harm the fetus. If you are pregnant or think you may be pregnant, consult your doctor before starting to take bosutinib.

Women taking bosutinib should be advised to use effective contraceptive methods during treatment and for at least 1 month after the last dose. Vomiting and diarrhea may reduce the effectiveness of oral contraceptives.

Request information on sperm preservation before starting treatment, if desired, due to the risk of reduced fertility during treatment with bosutinib.

If you are breastfeeding, inform your doctor. Do not breastfeed during treatment with bosutinib, as it may harm the baby.

Driving and operating machinery

If you experience dizziness, blurred vision, or unusual fatigue, do not drive or operate machinery until these adverse effects have disappeared.

Bosutinib Zentiva contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per tablet; it is essentially "sodium-free".

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

Bosutinib will only be prescribed by a doctor experienced in using medications to treat leukemia.

Dose and Administration Form

The recommended dose is 400 mg once a day for patients with newly diagnosed LMC. The recommended dose is 500 mg once a day for patients whose previous medications for treating LMC have not been effective or are not suitable. In case of moderate or severe kidney problems, your doctor will reduce the dose by 100 mg once a day for moderate kidney problems and an additional 100 mg once a day for severe kidney problems. Your doctor may adjust the dose using 100 mg tablets, based on your health status, in response to treatment, and/or adverse effects you may experience. Take the tablet(s) once a day, with food. Swallow the tablet(s) whole with a little water.

If you take more Bosutinib Zentiva than you should

If you accidentally take too many bosutinib tablets or a higher dose than you need, go to a doctor immediately. If possible, show the doctor the packaging or this leaflet. You may need medical attention.

If you forget to take Bosutinib Zentiva

If less than 12 hours have passed, take the recommended dose. If more than 12 hours have passed, take your next dose at the usual time the next day.

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

If you interrupt treatment with Bosutinib Zentiva

Do not stop taking bosutinib unless your doctor tells you to. If you cannot take the medication as indicated by your doctor or think you no longer need it, consult your doctor immediately.

If you have any other questions about using this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

You should consult your doctor immediately if you experience any severe side effects (see also section 2 “What you need to know before starting to take Bosutinib Zentiva”):

Blood disorders. Inform your doctor immediately if you experience any of the following symptoms: bleeding, fever, or frequent rashes (you may have a blood or lymphatic system disorder).

Liver disorders. Inform your doctor immediately if you experience any of the following symptoms: itching, yellow eyes or skin, dark urine, and stomach pain or discomfort, or fever.

Stomach/intestinal disorders. Inform your doctor if you experience stomach pain, heartburn, diarrhea, constipation, nausea, or vomiting.

Cardiac problems. Inform your doctor if you experience any cardiac alteration, such as an abnormal electrical signal called “prolongation of the QT interval”, or if you faint (lose consciousness) or experience irregular heartbeats during bosutinib treatment.

Reactivation of hepatitis B virus. Recurrence (reactivation) of hepatitis B infection if you have had hepatitis B in the past (a liver infection).

Severe skin reactions. Inform your doctor immediately if you experience any of the following symptoms: painful red or purple rash that spreads and if blisters and/or other lesions appear on the mucous membrane (e.g., mouth and lips).

The side effects that may appear with bosutinib are:

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

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

Rare side effects (may affect up to 1 in 100 patients):

Unknown frequency (cannot be estimated from available data):

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side 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.

This medication does not require special storage conditions.

Do not use this medication if you observe that the packaging is deteriorated or shows signs of having been manipulated.

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications you no longer need at the Sigre Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

Composition ofBosutinib Zentiva

• The active ingredient is bosutinib. Bosutinib Zentiva film-coated tablets are available in different doses.

Bosutinib Zentiva 100 mg: each film-coated tablet contains 100 mg of bosutinib.

Bosutinib Zentiva 400 mg: each film-coated tablet contains 400 mg of bosutinib.

Bosutinib Zentiva 500 mg: each film-coated tablet contains 500 mg of bosutinib.

• The other components are: microcrystalline cellulose (E460), sodium croscarmellose (E468), anhydrous colloidal silica, magnesium stearate. The coating of the tablet contains polyvinyl alcohol (E1203), macrogol, talc (E553b), titanium dioxide (E171), and yellow iron oxide (E172, in Bosutinib Zentiva 100 mg and 400 mg), red iron oxide (E172, in Bosutinib Zentiva 400 mg and 500 mg).

Appearance of the product and contents of the package

Bosutinib Zentiva 100 mg film-coated tablets are yellow in color and oval-shaped, biconvex, engraved with “C18” on one side.

Bosutinib Zentiva 100 mg is available in blisters containing 28 or 112 film-coated tablets or in perforated single-dose blisters containing 28x1 or 112x1 film-coated tablets.

Bosutinib Zentiva 400 mg film-coated tablets are orange in color and oval-shaped, biconvex, engraved with “C19”.

Bosutinib Zentiva 400 mg is available in blisters containing 28 film-coated tablets or in perforated single-dose blisters containing 28x1 film-coated tablets.

Bosutinib Zentiva 500 mg film-coated tablets are pink in color and oval-shaped, biconvex, engraved with “C20” on one side.

Bosutinib Zentiva 500 mg is available in blisters containing 28 film-coated tablets or in perforated single-dose blisters containing 28x1 film-coated tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder

Zentiva, k.s.

U Kabelnovy 130

Dolni Mecholupy

102 37 Prague 10

Czech Republic

Responsible for manufacturing

Coripharma ehf.

Reykjavikurvegur 78

IS -220 Hafnarfjordur

Iceland

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

Zentiva Spain S.L.U.

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

28224 Pozuelo de Alarcón, Madrid

Spain

This medicine is authorized in the member states of the European Economic Area with the following names:

Last review date of this leaflet: January 2024

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