Bosutinib Sandoz

Patient Information Leaflet

Bosutinib Sandoz 100 mg film-coated tablets, 400 mg film-coated tablets, 500 mg film-coated tablets

Equivalent medicine
Please read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if they have the same symptoms as yours, because it may be harmful to them.
• If you experience any side effect, including any not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet:

1. What Bosutinib Sandoz is and what it is used for
2. What you need to know before you take Bosutinib Sandoz
3. How to take Bosutinib Sandoz
4. Possible side effects
5. How to store Bosutinib Sandoz
6. Contents of the pack and other information

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

Bosutinib Sandoz contains the active substance bosutinib. Bosutinib Sandoz is used to treat adult and pediatric patients aged 6 years and older who have a type of leukemia called Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase (CP), either newly diagnosed or for whom previous treatments for chronic myeloid leukemia have failed or were unsuitable. It is also used to treat adult patients with Ph+ chronic myeloid leukemia in the accelerated phase (AP) and blast phase (BP) for whom previous treatments for chronic myeloid leukemia have failed or were unsuitable.

In patients with Ph+ chronic myeloid leukemia, a genetic alteration in the DNA (genetic material) activates a signal that causes the body to produce an excessive number of a specific type of white blood cells called granulocytes. This medicine blocks that signal and thereby stops the production of these cells.

If you have any questions about how Bosutinib Sandoz works or why this medicine has been prescribed for you, please consult your doctor.

2. What you should know before taking Bosutinib Sandoz

Do not take Bosutinib Sandoz:

• if you are allergic to bosutinib or to any of the other ingredients of this medicine (listed in section 6).
• if your doctor has told you that you have impaired liver function or liver damage.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Bosutinib Sandoz:

• if you have or have previously had liver problems. Inform your doctor if you have had liver problems in the past, including hepatitis (liver infection or inflammation) of any kind, or if you have previously experienced any signs or symptoms of liver problems (see section 4, “Possible side effects”), as Bosutinib Sandoz may affect your liver function. Your doctor will perform blood tests to monitor your liver function before starting treatment with Bosutinib Sandoz, during the first 3 months of treatment, and whenever clinically indicated.
• if you have diarrhoea or vomiting. Inform your doctor if you develop any signs or symptoms of stomach or intestinal problems (see section 4, “Possible side effects”). To reduce symptoms, your doctor may prescribe an anti-diarrhoeal or antiemetic medication and/or fluids. Your doctor may also temporarily suspend, reduce the dose, or permanently discontinue treatment with this medicine (see section 3, “How to take Bosutinib Sandoz”). Ask your doctor whether medications for nausea or vomiting taken together with Bosutinib Sandoz may increase your risk of developing cardiac arrhythmias.
• if you have bleeding problems. Inform your doctor if you develop signs or symptoms of blood-related problems (see section 4, “Possible side effects”), as this medicine reduces your body’s ability to stop bleeding. Your doctor will perform a complete blood count weekly during the first month, then monthly. Your doctor may also temporarily suspend, reduce the dose, or permanently discontinue treatment with this medicine (see section 3, “How to take Bosutinib Sandoz”).
• if you have an infection. Inform your doctor if you develop any of the following signs or symptoms, such as fever, problems with urination (e.g. burning sensation when urinating), new onset of cough, or new onset of sore throat, as this medicine reduces your body’s ability to fight infections.
• if you have fluid retention. Inform your doctor if you develop any of the following signs or symptoms of fluid retention during treatment with Bosutinib Sandoz, such as swelling of the ankles, feet, or legs, difficulty breathing, chest pain, or cough (these may be signs of fluid accumulation in the lungs or chest). Your doctor will monitor for fluid retention and manage any symptoms.
• if you have heart problems. Inform your doctor if you have a heart condition, such as heart failure or reduced blood flow to the heart that could lead to a heart attack. Seek immediate medical attention if you experience shortness of breath, rapid weight gain, chest pain, or swelling in your hands, ankles, or feet.
• if you have been diagnosed with an abnormal heart rhythm. Inform your doctor if you have arrhythmias or an abnormal electrical signal known as “QT interval prolongation.” This is particularly important if you experience frequent or prolonged diarrhoea, as described above. If you faint (lose consciousness) or have an irregular heartbeat while taking this medicine, inform your doctor immediately, as this may indicate a serious heart condition (see section 2, “What you should know before taking Bosutinib Sandoz”). Before starting treatment, your doctor will perform an electrocardiogram (ECG). Your doctor will perform blood tests before and during treatment, and if you have low levels of potassium or magnesium, you will be prescribed treatment to correct these low levels.
• if you have been told you have kidney problems. Inform your doctor if you urinate more frequently and produce larger amounts of pale-coloured urine, or if you urinate less frequently and produce smaller amounts of dark-coloured urine. Also, inform your doctor if you are losing weight or have swelling in your feet, ankles, legs, hands, or face. Your doctor will assess kidney function before treatment and monitor it closely during treatment with this medicine.
• if you have had or may currently have hepatitis B infection. This medicine may cause reactivation of hepatitis B, which in some cases can be fatal. Before starting treatment, your doctor will test you for this infection. If you have this infection, your doctor will closely monitor you for signs and symptoms during treatment and for several months after stopping treatment.
• if you have had or currently have pancreas problems. Inform your doctor if you develop abdominal pain or discomfort. If you experience abdominal pain and blood tests show elevated levels of lipase, an enzyme that helps your body break down fats in food, your doctor may discontinue treatment and perform tests to rule out pancreas problems.
• if you develop any of the following symptoms: severe skin rash. Inform your doctor if you develop any of the following signs or symptoms of a painful red or purplish rash that spreads progressively, along with blisters and/or other lesions starting on mucous membranes (e.g. mouth and lips). If a severe skin reaction occurs during treatment, your doctor will permanently discontinue treatment.
• if you experience any of the following symptoms: flank pain, blood in the urine, or reduced urine output. In severe cases, your body may be unable to eliminate waste products from dead tumour cells. This condition is known as tumour lysis syndrome and may cause kidney failure and heart problems within 48 hours of the first dose of this medicine. Your doctor is aware of this risk and may ensure you receive adequate hydration and possibly other medications to prevent this condition. Before starting treatment, your doctor will perform a blood test to check for high levels of uric acid and prescribe treatment to correct these levels.

Sun protection / UV exposure
While taking bosutinib, you may become more sensitive to sunlight or UV radiation. It is important to cover
exposed skin areas and use sunscreen with a high sun protection factor (SPF).
Patients of Asian origin
If you are of Asian origin, you may have a higher risk of experiencing side effects during treatment with this
medicine. Your doctor will monitor you closely for serious side effects, especially when increasing the dose.
Children and adolescents
Bosutinib Sandoz is not recommended for individuals under 6 years of age. This medicine has not been studied
in children under 1 year of age.
Other medicines and Bosutinib Sandoz
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines,
including over-the-counter medicines, vitamins, and herbal supplements. Some medicines may affect bosutinib
levels in your body. You must inform your doctor if you are taking medicines containing any of the following
active substances:
The following active substances may increase the risk of side effects from Bosutinib Sandoz:

• 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 people with high blood pressure.
• ritonavir, lopinavir/ritonavir, indinavir, nelfinavir, saquinavir, atazanavir, amprenavir, fosamprenavir, and darunavir, used to treat HIV/AIDS infections.
• boceprevir and telaprevir, used to treat hepatitis C.
• aprepitant, used to prevent and control nausea and vomiting.
• imatinib, used to treat a type of leukaemia.
• 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 Sandoz:

• 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 (Hypericum perforatum, an herbal preparation sold without prescription), used to treat depression.
• efavirenz and etravirine, used to treat human immunodeficiency virus (HIV)/AIDS infections.
• modafinil, used to treat certain types of sleep disorders.

These medicines should be avoided during treatment with Bosutinib Sandoz. If you are taking any of these
medicines, inform your doctor. Your doctor may adjust the dose of these medicines, adjust the dose of
Bosutinib Sandoz, or prescribe a different medicine.
The following active substances may alter heart rhythm:

• amiodarone, disopyramide, procainamide, quinidine, and sotalol, used to treat heart conditions.
• chloroquine and halofantrine, used to treat malaria.
• clarithromycin and moxifloxacin, 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 breast milk production.
• methadone, used to treat pain.

These medicines should be used with caution during treatment with Bosutinib Sandoz. If you are taking any of
these medicines, inform your doctor.
Agents that reduce stomach acidity
Proton pump inhibitors (PPIs) should be used with caution during treatment with Bosutinib Sandoz, as they
may reduce its effectiveness. Your doctor may consider short-acting antacids as an alternative to PPIs, and, if
possible, the administration times of Bosutinib Sandoz and antacids should be separated (e.g. take Bosutinib
Sandoz in the morning and antacids in the evening).
The medicines listed here may not be the only ones that interact with Bosutinib Sandoz; if you are unsure whether
the information above applies to you or your child, consult your doctor.
Bosutinib Sandoz with food and alcohol
Do not take Bosutinib Sandoz with grapefruit or grapefruit juice, as it may increase the risk of side effects.
Pregnancy, breastfeeding, and fertility
Bosutinib Sandoz must not be used during pregnancy unless considered necessary, as it may harm the unborn
baby. Consult your doctor before taking this medicine if you are pregnant or could become pregnant.
Women taking Bosutinib Sandoz should use an effective method of contraception during treatment and for at
least 1 month after the last dose. Vomiting or diarrhoea may reduce the effectiveness of oral contraceptives.
Treatment with Bosutinib Sandoz may reduce fertility; therefore, you may wish to discuss sperm preservation
before starting treatment.
If you are breastfeeding, inform your doctor. Do not breastfeed during treatment with this medicine, as it may harm
the baby.
Driving and using machines
If you experience dizziness, blurred vision, or unusual tiredness, do not drive or operate machinery until these
side effects have resolved.

3. How to take Bosutinib Sandoz

Take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.
This medicine will only be prescribed to you by a doctor experienced in medicines used to treat leukaemia.

Dosage and method of administration
Adults
The recommended dose is 400 mg once daily for patients with newly diagnosed chronic myeloid leukaemia. The recommended dose is 500 mg once daily for patients for whom previous treatments for chronic myeloid leukaemia have not worked or are not suitable. If you are unable to tolerate the recommended dose or do not respond adequately to Bosutinib Sandoz, your doctor may further adjust your dose.

Children and adolescents (from 6 years of age)
The recommended dose is 300 mg/m\² of body surface area once daily in paediatric patients with newly diagnosed disease. The recommended dose is 400 mg/m\² of body surface area once daily in paediatric patients who are resistant or intolerant.

Dose recommendations are provided in the table below. Depending on the case, the recommended dose may be achieved by combining different strengths of bosutinib film-coated tablets.

Dosage of bosutinib for newly diagnosed (ND) paediatric patients and for resistant or intolerant (R/I) paediatric patients

* maximum initial dose (corresponding to the maximum initial dose in the indication for adults)
If you are unable to tolerate the recommended dose or do not respond adequately to Bosutinib Sandoz,
your doctor may further adjust the dose.
Take the tablet(s) once daily with food. Swallow the tablet whole with water.
If you take more Bosutinib Sandoz than you should
If you accidentally take too many Bosutinib Sandoz tablets or a higher dose than required,
seek immediate medical advice. If possible, show the doctor the packaging or
this leaflet. You may require medical treatment.
If you forget to take Bosutinib Sandoz
If less than 12 hours have passed since the scheduled dosing time, take the recommended dose. If
more than 12 hours have passed, take the next dose at the usual time the following day. Do not take a
double dose to make up for the missed tablets.
If you stop taking Bosutinib Sandoz
Do not stop taking Bosutinib Sandoz unless instructed by your doctor. If you are unable to take the
medication as prescribed or feel you no longer need it, contact your doctor immediately.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects

You should contact your doctor immediately if you experience any of the following serious side effects (also see section 2, "What you need to know before taking Bosutinib Sandoz"):

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

• Reduction in the number of platelets (thrombocytopenia), red blood cells (anemia), and/or neutrophils (a type of white blood cells) (neutropenia), which may cause abnormal bleeding, fever, or bruising without injury (you may have a disorder of the blood or lymphatic system) (see section 2, "What you need to know before taking Bosutinib Sandoz").
• Fluid around the lungs (pleural effusion).

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

• Low white blood cell count (leukopenia).
• Bleeding from the stomach or intestines (gastrointestinal haemorrhage), which may include blood in vomit, stools (bowel movements), or urine, or black stools (black, tarry bowel movements) (see section 2, "What you need to know before taking Bosutinib Sandoz").
• Chest pain.
• Toxic liver damage (hepatotoxicity), abnormal liver function, including liver disorders (abnormal liver function), which may be accompanied by itching, yellowing of the eyes or skin, dark urine, pain or discomfort in the upper right part of the stomach, or fever (see section 2, "What you need to know before taking Bosutinib Sandoz").
• When the heart does not pump blood properly (heart failure).
• When there is reduced blood flow to the heart (cardiac ischemia).
• Lung infection (pneumonia).
• Abnormal heart rhythm (prolonged QT on electrocardiogram), which may lead to fainting, dizziness, and palpitations.
• Increased blood pressure (hypertension).
• High levels of potassium in the blood (hyperkalemia).
• Acute kidney failure, kidney failure, impaired kidney function.
• Fluid around the heart (pericardial effusion).
• Allergic reaction (drug hypersensitivity).
• Abnormally high blood pressure in the arteries of the lungs (pulmonary hypertension).
• Acute inflammation of the pancreas (acute pancreatitis).

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

• Fever associated with low white blood cell count (febrile neutropenia).
• Liver damage (liver injury).
• Potentially life-threatening allergic reaction (anaphylactic shock).
• Abnormal accumulation of fluid in the lungs (acute pulmonary edema).
• Skin rash (drug rash).
• Scaly and peeling skin rash (exfoliative rash).
• Inflammation of the membrane lining the heart (pericarditis).
• Marked reduction in the number of granulocytes (a type of white blood cells, granulocytopenia).
• Severe skin disorder (erythema multiforme).
• Nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, cloudy urine, and fatigue associated with abnormal laboratory test results (high levels of potassium, uric acid, and phosphorus, and low levels of calcium in the blood), which may lead to changes in kidney function and acute kidney failure (tumour lysis syndrome (TLS)).
• Respiratory failure.

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

• Severe skin disease (Stevens-Johnson syndrome, toxic epidermal necrolysis), which may include painful red or purplish rash that spreads and forms blisters and/or other lesions starting in mucous membranes (e.g., mouth and lips) due to an allergic reaction.
• Interstitial lung disease (a condition causing scarring in the lungs): signs include cough, difficulty breathing, painful breathing.
• Reactivation of hepatitis B infection if you have previously had hepatitis B (a liver infection).

Other side effects of Bosutinib Sandoz may include:

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

• Diarrhoea, vomiting, stomach ache (abdominal pain), nausea.
• Fever (pyrexia), swelling of the hands, feet or face (oedema), fatigue, weakness.
• Respiratory tract infection.
• Nasopharyngitis.
• Changes in blood tests indicating that this medicine is affecting the liver (increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST)) and/or the pancreas (increased lipase), and the kidneys (increased blood creatinine).
• Decreased appetite.
• Joint pain (arthralgia), back pain.
• Headache.
• Skin rash, which may be itchy and/or widespread (rash).
• Cough.
• Shortness of breath (dyspnoea).
• Feeling unsteady (dizziness).

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

• Stomach irritation (gastritis).
• Pain.
• Influenza, bronchitis.
• Changes in blood tests indicating that this medicine is affecting the heart (increased blood creatine phosphokinase), the liver (increased blood bilirubin, increased gamma-glutamyl transferase (GGT)) and/or the pancreas (increased amylase).
• Low level of phosphorus in the blood (hypophosphataemia), excessive loss of body fluids (dehydration).
• Muscle pain (myalgia).
• Altered sense of taste (dysgeusia).
• Ringing in the ears (tinnitus).
• Hives, acne.
• Sensitivity to UV rays from sunlight and other light sources (photosensitivity reaction).
• Itching.

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Bosutinib Sandoz

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after "Exp.".
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Bosutinib Sandoz contains

• The active substance is bosutinib. The film-coated tablets are available in different strengths. Bosutinib Sandoz 100 mg film-coated tablets contain 100 mg of bosutinib (as dihydrate). Bosutinib Sandoz 400 mg film-coated tablets contain 400 mg of bosutinib (as dihydrate). Bosutinib Sandoz 500 mg film-coated tablets contain 500 mg of bosutinib (as dihydrate).
• The other components are: microcrystalline cellulose, crospovidone, poloxamer, povidone, magnesium stearate. The tablet coating contains hypromellose, titanium dioxide, macrogol, yellow iron oxide (for the 100 mg and 400 mg tablets), red iron oxide (for the 400 mg and 500 mg tablets) and talc (for the 500 mg tablet).

Description of the appearance of Bosutinib Sandoz and contents of the pack
Bosutinib Sandoz 100 mg film-coated tablets are yellow, oval-shaped, approximately 5.41 mm wide and 10.61 mm long, biconvex, with "100" engraved on one side and "B" on the other.
Bosutinib Sandoz 100 mg film-coated tablets are available in blisters packed in cardboard boxes containing 28, 30 or 112 film-coated tablets, or in unit dose divisible blisters packed in cardboard boxes containing 28 x 1, 30 x 1 or 112 x 1 film-coated tablets.
Bosutinib Sandoz 400 mg film-coated tablets are orange, oval-shaped, approximately 8.66 mm wide and 16.17 mm long, biconvex, with "400" engraved on one side and "B" on the other.
Bosutinib Sandoz 500 mg film-coated tablets are red, oval-shaped, approximately 9.37 mm wide and 18.20 mm long, biconvex, with "500" engraved on one side and "B" on the other.
Bosutinib Sandoz 400 mg and 500 mg film-coated tablets are available in blisters packed in cardboard boxes containing 28 or 30 film-coated tablets, or in unit dose divisible blisters packed in cardboard boxes containing 28 x 1 or 30 x 1 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sandoz S.p.A.
Viale Luigi Sturzo 43
20154 Milan
Italy

Manufacturer
Pharmadox Healthcare Limited,
Kw20a Kordin Industrial Park
PLA 3000 Paola
Malta
Salutas Pharma GmbH
Otto-Von-Guericke-Allee 1
39179 Barleben
Germany
Lek Pharmaceuticals d.d.
Verovškova ulica 57
1526 Ljubljana
Slovenia

This medicinal product is authorised in the European Economic Area member states under the following names:
Austria Bosutinib Sandoz 100 mg Filmtabletten
Bosutinib Sandoz 400 mg Filmtabletten
Bosutinib Sandoz 500 mg Filmtabletten
Belgium Bosutinib Sandoz 100 mg filmomhulde tabletten
Bosutinib Sandoz 400 mg filmomhulde tabletten
Bosutinib Sandoz 500 mg filmomhulde tabletten
Croatia Bosutinib Sandoz 100 mg filmom obložene tablete
Bosutinib Sandoz 500 mg filmom obložene tablete
Denmark Bosutinib Sandoz
France BOSUTINIB SANDOZ 100 mg, comprimé pelliculé
BOSUTINIB SANDOZ 400 mg, comprimé pelliculé
BOSUTINIB SANDOZ 500 mg, comprimé pelliculé
Ireland Bosutinib Rowex 100 mg film-coated tablets
Bosutinib Rowex 400 mg film-coated tablets
Bosutinib Rowex 500 mg film-coated tablets
Italy Bosutinib Sandoz
Poland Bosutinib Sandoz
Norway Bosutinib Sandoz
Sweden Bosutinib Sandoz
Bosutinib Sandoz 100 mg filmtabletta
Hungary Bosutinib Sandoz 400 mg filmtabletta
Bosutinib Sandoz 500 mg filmtabletta