Package leaflet: Information for the user

Bosutinib Stada, 100 mg, film-coated tablets
Bosutinib Stada, 400 mg, film-coated tablets
Bosutinib Stada, 500 mg, film-coated tablets
Bosutinibum
Please read this leaflet carefully before taking this medicine, because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any further questions, please ask your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else even if their symptoms are the same.
If you experience any side effects, including any not listed in this leaflet, tell your doctor. See section 4.

Leaflet contents

What Bosutinib Stada is and what it is used for
Important information before taking Bosutinib Stada
How to take Bosutinib Stada
Possible side effects
How to store Bosutinib Stada
Contents of the pack and other information

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

Bosutinib Stada contains the active substance bosutinib. This medicine is used to treat
adult patients with a type of leukaemia called chronic myeloid leukaemia with the
Philadelphia chromosome (Ph-positive). It is used either in patients who have just been
diagnosed or in patients who previously received other treatments for chronic myeloid
leukaemia that were ineffective or inappropriate. Ph-positive chronic myeloid leukaemia 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 Stada works or why this
medicine has been prescribed, please consult your doctor.

2. Important information before taking Bosutinib Stada

When not to take Bosutinib Stada

if the patient is allergic to bosutinib or any of the other ingredients of this medicine (listed in section 6);
if the patient has been informed by their doctor that they have impaired liver function.

Warnings and precautions
Before starting treatment with Bosutinib Stada, discuss this with your doctor, pharmacist,
or nurse:

if the patient has or has previously had liver disease. Inform the doctor about any prior liver conditions, including inflammation (infection or inflammatory state) of the liver regardless of type, as well as any previous occurrence of the following signs and symptoms related to the liver: itching, yellowing of the whites of the eyes or skin, dark urine, or pain or discomfort in the upper right part of the abdomen. Before starting treatment with Bosutinib Stada and during the first 3 months of treatment with Bosutinib Stada, and whenever clinically indicated, the doctor should perform blood tests to monitor liver function.
if the patient has diarrhoea or vomiting. Inform the doctor if any of the following signs or symptoms occur: an increase in the number of daily bowel movements (defecations) beyond normal levels, increased episodes of vomiting, presence of blood in vomit, stools (defecations), or urine, or black stools (tarry-black defecations). Ask the doctor whether antiemetic treatment could increase the risk of developing cardiac arrhythmias. Consult the doctor, especially if treatment for nausea and (or) vomiting includes a medicine containing domperidone. Treating nausea or vomiting with such medicines together with Bosutinib Stada may increase the risk of serious cardiac arrhythmias.
if the patient experiences bleeding. Inform the doctor about any signs or symptoms such as abnormal bleeding or bruising without prior injury.
if the patient has an infection. Inform the doctor about any signs or symptoms such as fever, problems with urination (e.g. burning sensation), new cough, or sore throat.
if the patient has fluid retention. Inform the doctor if any of the following signs or symptoms of fluid retention occur during treatment with Bosutinib Stada: swelling of the ankles, feet, or legs, difficulty breathing, chest pain, or cough (which may indicate fluid accumulation in the lungs or chest cavity).
if the patient has heart conditions. Inform the doctor about any heart diseases, such as arrhythmias or abnormal findings on ECG known as "QT prolongation". These conditions are always important but are particularly significant in cases of frequent or prolonged diarrhoea, as described above. If fainting (loss of consciousness) or irregular heartbeat occurs while taking Bosutinib Stada, contact the doctor immediately, as this may indicate a serious heart condition.
if the patient has been diagnosed with kidney disease. Inform the doctor about urinating more frequently and producing larger amounts of pale-coloured urine, or urinating less frequently and producing smaller amounts of dark-coloured urine. Also inform the doctor about weight loss and swelling of the feet, ankles, legs, hands, or face.
if the patient has ever had or may currently have hepatitis B virus infection. This is because Bosutinib Stada may cause reactivation of hepatitis B virus infection, which in some cases may lead to death; patients will be closely monitored by the doctor for signs of this infection before starting treatment.
if the patient has or has had pancreatic diseases. Inform the doctor about the occurrence of abdominal pain or discomfort in this area.
if the patient develops any of the following symptoms: severe skin rashes. Inform the doctor if any of the following symptoms occur: painful, red or purple spreading rash, blisters and (or) other changes starting in the mucous membranes (e.g. inside the mouth or lips).
if the patient notices any of the following symptoms: flank pain, blood in the urine
or reduced urine output. In very severe illness, the body may be unable to eliminate all components from dying tumour cells. This complication is called tumour lysis syndrome and may lead to kidney failure and heart problems within 48 hours after the first dose of Bosutinib Stada. The doctor is aware of the possibility of this complication and may recommend adequate hydration and other medicines to prevent its occurrence.
Protection from sunlight/UV radiation
While taking bosutinib, the patient may become more sensitive to sunlight or UV radiation. It is important to cover skin areas exposed to sunlight and to use high sun protection factor (SPF) sunscreen.
Children and adolescents
Bosutinib Stada is not recommended for use in individuals under 18 years of age. The use of this medicine has not been studied in children and adolescents.
Bosutinib Stada and other medicines
Tell your doctor or pharmacist about all medicines currently or recently taken, including those obtained without a prescription, vitamins, and herbal medicines, as well as any medicines planned for future use. Some medicines may affect bosutinib levels in the patient's body. Inform the doctor about taking any medicines containing the following active substances.
The following active substances may increase the risk of adverse effects of Bosutinib Stada:
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 lower blood pressure in patients with hypertension,
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 and control nausea and vomiting,
imatinib used to treat one type of leukaemia,
crizotinib used to treat one type of lung cancer known as non-small cell lung cancer.
The following active substances may reduce the effectiveness of Bosutinib Stada:
rifampicin used to treat tuberculosis,
phenytoin and carbamazepine used to treat epilepsy,
bosentan used to treat 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 prescription) used to treat depression,
efavirenz and etravirine used to treat HIV/AIDS infections,
modafinil used to treat certain types of sleep disorders.

Avoid using these medicines during treatment with Bosutinib Stada. Inform the doctor if any of these medicines are being taken. The doctor may adjust the doses of these medicines, the dose of Bosutinib Stada, or switch to another medicine.
The following active substances may affect heart rhythm:

amiodarone, disopyramide, procainamide, quinidine, and sotalol used to treat heart disorders,
chloroquine, 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.

Exercise caution when taking these medicines during treatment with Bosutinib Stada. Inform the doctor if any of these medicines are being taken.
Other medicines not listed above may also interact with Bosutinib Stada.
Taking Bosutinib Stada with food and drink
Do not take Bosutinib Stada with grapefruit or grapefruit juice, as this may increase the risk of adverse effects.
Pregnancy, breastfeeding, and fertility
Bosutinib Stada may harm an unborn child; therefore, it should not be taken during pregnancy unless considered necessary. If pregnant or if there is a possibility of becoming pregnant, consult a doctor before taking Bosutinib Stada.
Women taking Bosutinib Stada are advised to use an effective method of contraception during treatment and for at least one month after the last dose. Vomiting and diarrhoea may reduce the effectiveness of oral contraceptives.
Due to the risk of reduced fertility in men, sperm preservation should be considered before starting treatment with Bosutinib Stada.
If the patient is breastfeeding, inform the doctor. Breastfeeding should not be continued during treatment with Bosutinib Stada, as it may harm the infant.
Driving and operating machinery
If the patient experiences dizziness, blurred vision, or unusual tiredness, they should not drive or operate machinery until these adverse effects have resolved.
Bosutinib Stada contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. the medicine is considered "sodium-free".

3. How to take Bosutinib Stada

This medicine should always be taken exactly as your doctor has instructed. If you are unsure,
consult your doctor or pharmacist.
Bosutinib Stada will only be prescribed by a doctor experienced in medicines used to treat
leukemia.
Dosage 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 who previously failed or were intolerant to treatment for
chronic myeloid leukemia is 500 mg once daily. For patients with moderate or severe renal
impairment, the doctor will reduce the dose by 100 mg per day in case of moderate renal
impairment and by an additional 100 mg per day in case of severe renal impairment.
Your doctor may adjust the dose using 100 mg tablets depending on your condition, your response to
treatment, and/or the occurrence of possible adverse effects. The tablets should be taken once daily
with food. Swallow the tablets whole with water.
If you take more Bosutinib Stada than you should
If you accidentally take more tablets or a higher dose than recommended, contact your doctor
immediately. If possible, show the doctor the medicine package or this leaflet. You may require
medical attention.
If you forget to take Bosutinib Stada
If less than 12 hours have passed since the missed dose, take the recommended dose. If more than
12 hours have passed since the missed dose, take the next dose at the usual time on the following
day.
Do not take a double dose to make up for a missed tablet.
Stopping Bosutinib Stada
Do not stop taking Bosutinib Stada unless your doctor tells you to. If you are unable to take the
medicine as directed, or if you think you no longer need the medicine, contact your doctor
immediately.
If you have any further questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the following serious adverse reactions occur,
contact your doctor immediately (see also section 2 "Important information before taking
Bosutinib Stada"):

Blood disorders. Immediately inform your doctor if you experience any of the following symptoms: bleeding, fever, or easy bruising (these may indicate a disease of the blood or lymphatic system).

Liver disorders. Immediately inform your doctor if you experience any of the following symptoms: itching, yellowing of the whites of the eyes or skin, dark-coloured urine, pain or discomfort in the upper right part of the abdomen, or fever.

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

Heart conditions. Inform your doctor if you experience heart problems such as abnormal electrical signals called "QT prolongation", fainting (loss of consciousness), or irregular heartbeat while taking Bosutinib Stada.

Reactivation of hepatitis B virus infection. Recurrence (reactivation) of hepatitis B virus infection (liver infection) in patients who have previously had this disease.

Severe skin reactions. Immediately inform your doctor if you develop any of the following symptoms: painful, red or purple spreading rash, blisters and/or other changes starting in the mucous membranes (e.g. inside the mouth or lips).

Adverse reactions associated with taking Bosutinib Stada may include:

Very common adverse reactions (may occur in more than 1 in 10 people):

decrease in the number of platelets, red blood cells, and/or neutrophils (a type of white blood cells)
diarrhoea, vomiting, abdominal pain, nausea
fever, swelling of hands, feet or face, fatigue, weakness
respiratory tract infection
inflammation of the nose and throat
changes in blood test results used to monitor whether Bosutinib Stada is affecting the liver and/or pancreas, kidneys
loss of appetite
joint pain, back pain
headache
skin rash, which may be itchy and/or widespread
cough
shortness of breath
feeling of imbalance (dizziness)
presence of fluid in the lungs (pleural effusion)
itching.

Common adverse reactions (may occur in up to 1 in 10 people):

low number of white blood cells (leukopenia)
gastritis (inflammation of the stomach), bleeding from the stomach or intestines
chest pain, pain
toxic liver damage, abnormal liver function, including impaired liver function
lung infection (pneumonia), influenza, bronchitis
heart rhythm disorders predisposing to fainting, dizziness, and palpitations
increased blood pressure
high potassium levels in the blood, low phosphate levels in the blood, excessive loss of body fluids (dehydration)
muscle pain
altered sense of taste (taste disturbance)
acute kidney failure, kidney failure, kidney function disorders
accumulation of fluid around the heart (pericardial effusion)
tinnitus (ringing in the ears)
urticaria (hives), acne
hypersensitivity reaction to light (sensitivity to UV rays from sunlight and other light sources)
allergic reaction
abnormally high blood pressure in the pulmonary arteries (pulmonary hypertension)
acute pancreatitis
respiratory failure.

Uncommon adverse reactions (may occur in up to 1 in 100 people):

fever associated with low white blood cell count (neutropenic fever)
liver damage
life-threatening allergic reaction (anaphylactic shock)
abnormal accumulation of fluid in the lungs (acute pulmonary oedema)
skin eruptions
inflammation of the sac-like membrane surrounding the heart (pericarditis)
marked decrease in granulocytes (a type of white blood cells)
severe skin disorders (erythema multiforme)
nausea, shortness of breath, irregular heartbeat, muscle cramps, 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 – tumour lysis syndrome
inflammation of blood vessels in the skin, which may lead to rash or bruising (cutaneous vasculitis).

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

severe skin disorders (Stevens-Johnson syndrome, toxic epidermal necrolysis) due to allergic reaction, peeling rash
interstitial lung disease (disorders causing lung scarring): symptoms include cough, difficulty breathing, painful breathing.

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed
in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions
can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Bosutinib Stada

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and the carton:
Expiry date (EXP). The expiry date refers to the last day of the stated month.
No special storage conditions apply for this medicine.
Do not use this medicine if you notice damage to the packaging or any signs of tampering.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Bosutinib Stada contains

The active substance is bosutinib. Bosutinib Stada film-coated tablets are available in different strengths.
Bosutinib Stada 100 mg: each film-coated tablet contains 100 mg of bosutinib.
Bosutinib Stada 400 mg: each film-coated tablet contains 400 mg of bosutinib.
Bosutinib Stada 500 mg: each film-coated tablet contains 500 mg of bosutinib.
The other ingredients are: microcrystalline cellulose, sodium croscarmellose, colloidal anhydrous silica, magnesium stearate.
The tablet coating contains: polyvinyl alcohol (E 1203), macrogol, talc, titanium dioxide (E 171), yellow iron oxide (E 172) – for Bosutinib Stada 100 mg and 400 mg, and red iron oxide (E 172) – for Bosutinib Stada 400 mg and 500 mg.

What Bosutinib Stada looks like and contents of the pack
Bosutinib Stada 100 mg film-coated tablets are yellow, oval, biconvex tablets with the imprint “C18” on one side.
Bosutinib Stada 100 mg is available in blister packs containing 28 or 112 film-coated tablets in a cardboard carton.
Bosutinib Stada 100 mg is also available in perforated single-dose blisters containing 28x1 or 112x1 film-coated tablet in a cardboard carton.

Bosutinib Stada 400 mg film-coated tablets are orange, oval, biconvex tablets with the imprint “C19” on one side.
Bosutinib Stada 400 mg is available in blister packs containing 28 or 112 film-coated tablets in a cardboard carton.
Bosutinib Stada 400 mg is also available in perforated single-dose blisters containing 28x1 or 112x1 film-coated tablet in a cardboard carton.

Bosutinib Stada 500 mg film-coated tablets are pink, oval, biconvex tablets with the imprint “C20” on one side.
Bosutinib Stada 500 mg is available in blister packs containing 28 or 112 film-coated tablets in a cardboard carton.
Bosutinib Stada 500 mg is also available in perforated single-dose blisters containing 28x1 or 112x1 film-coated tablet in a cardboard carton.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
STADA Arzneimittel AG
Stadastrasse 2-18
61118 Bad Vilbel
Germany

Manufacturer
Coripharma ehf.
Reykjavíkurvegur 78
Hafnarfjörður 220
Iceland
STADA Arzneimittel AG
Stadastrasse 2-18
61118 Bad Vilbel
Germany
Clonmel Healthcare Ltd.
Waterford Road
Clonmel
E91 D768, Co. Tipperary
Ireland

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Stada Pharm Sp. z o.o.
ul. Krakowiaków 44
02-255 Warszawa
Tel. +48 22 737 79 20

This medicinal product is authorised in the European Economic Area countries under the following names:
Belgium Bosutinib EG 100 mg film-coated tablets
Bosutinib EG 400 mg film-coated tablets
Bosutinib EG 500 mg film-coated tablets
Denmark Bosutinib STADA
Finland Bosutinib STADA 100 mg film-coated tablets
Bosutinib STADA 400 mg film-coated tablets
Bosutinib STADA 500 mg film-coated tablets
France BOSUTINIB EG 100 mg, film-coated tablet
BOSUTINIB EG 400 mg, film-coated tablet
BOSUTINIB EG 500 mg, film-coated tablet
Spain Bosutinib Stada 100 mg film-coated tablets EFG
Bosutinib Stada 400 mg film-coated tablets EFG
Bosutinib Stada 500 mg film-coated tablets EFG
Netherlands Bosutinib CF 100 mg, film-coated tablets
Bosutinib CF 400 mg, film-coated tablets
Bosutinib CF 500 mg, film-coated tablets
Ireland Bosutinib Clonmel 100 mg film coated tablets
Bosutinib Clonmel 400 mg film coated tablets
Bosutinib Clonmel 500 mg film coated tablets
Iceland Bosutinib STADA
Luxembourg Bosutinib EG 100 mg film-coated tablets
Bosutinib EG 400 mg film-coated tablets
Bosutinib EG 500 mg film-coated tablets
Germany Bosutinib STADA 100 mg film tablets
Bosutinib STADA 400 mg film tablets
Bosutinib STADA 500 mg film tablets
Norway Bosutinib STADA 100 film-coated tablets
Bosutinib STADA 400 film-coated tablets
Bosutinib STADA 500 film-coated tablets
Sweden Bosutinib STADA 100 film-coated tablets
Bosutinib STADA 400 film-coated tablets
Bosutinib STADA 500 film-coated tablets

Bosutinib stada