Bosutinib Onkogen

Package Leaflet: Information for the User

Bosutinib Onkogen, 100 mg, coated tablets

Bosutinib Onkogen, 500 mg, coated tablets

Bosutinib

Read all of 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, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

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

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

Bosutinib Onkogen contains the active substance bosutinib. This medicine is used to treat adult patients with a type of blood cancer called chronic myelogenous leukemia (CML) with Philadelphia chromosome positive (Ph+), who have been newly diagnosed or whose previous treatment for CML has not worked or is not suitable. CML is a cancer of the blood in which the bone marrow produces too many white blood cells, called granulocytes.

2. Before you take Bosutinib Onkogen

When not to take Bosutinib Onkogen

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

Warnings and precautions

Before taking Bosutinib Onkogen, tell your doctor, pharmacist, or nurse:

• if you have or have had liver disease.Tell your doctor about any previous liver disease, including hepatitis (infection or inflammation) of any type, as well as any previous symptoms related to liver disease, 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 Onkogen and during the first 3 months of treatment with Bosutinib Onkogen, and as clinically indicated, your doctor should perform blood tests to check your liver function.

and during the first 3 months of treatment with Bosutinib Onkogen, and as clinically indicated, your doctor should perform blood tests to check your liver function.

• if you have diarrhea and vomiting.Tell your doctor about any of the following signs and symptoms: increased daily number of stools (bowel movements) beyond what is normal, increased number of vomiting episodes, blood in vomit, stools (bowel movements), or urine, or black stools (black, tarry stools). Ask your doctor if taking anti-vomiting medication may increase the risk of abnormal heart rhythms. 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 Onkogen may increase the risk of life-threatening abnormal heart rhythms.
• if you have bleeding.Tell your doctor about any symptoms such as abnormal bleeding or bruising without injury.
• if you have an infection.Tell your doctor about any symptoms such as fever, problems urinating (e.g., burning), new cough, or sore throat.
• if you have fluid retention.Tell your doctor if you experience any of the following symptoms of fluid retention while taking Bosutinib Onkogen: swelling of the ankles, feet, or legs, difficulty breathing, chest pain, or cough (these may be signs of fluid retention in the lungs or chest).
• if you have heart disease.Tell your doctor about heart disease, such as abnormal heart rhythms or abnormal EKG findings called "QT interval prolongation". These conditions are always important but are especially important if you have frequent or prolonged diarrhea, as described above. If you experience fainting (loss of consciousness) or irregular heartbeat while taking Bosutinib Onkogen, seek medical attention immediately, as this may be a sign of a serious heart condition.
• if you have kidney disease.Tell your doctor about more frequent urination and production of larger amounts of pale urine, as well as less frequent urination and production of smaller amounts of dark urine. Also, tell your doctor about 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 Onkogen may cause reactivation of hepatitis B virus infection, which can be fatal 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.Tell your doctor about abdominal pain or discomfort in this area.
• if you experience any of the following symptoms: severe skin rash.Tell your doctor if you experience any of the following symptoms: painful, red, or purple spreading rash, blisters, and/or other skin changes that start to appear on the mucous membranes (e.g., in the mouth and on the lips).
• if you notice any of the following symptoms: side pain, blood in urine, or decreased urine output.In severe cases, 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 taking the first dose of Bosutinib Onkogen. Your doctor is aware of the possibility of this complication and may recommend that you be properly hydrated, as well as administer other medications to prevent it.

Sun protection/UV radiation

While taking bosutinib, you may be more sensitive to sunlight or UV radiation. It is essential to cover exposed skin areas and use high SPF sunscreens.

Children and adolescents

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

Bosutinib Onkogen and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those obtained without a prescription, vitamins, and herbal medicines. Some medicines may affect the levels of Bosutinib Onkogen in your body. Tell your doctor about medicines containing the following active substances:

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

Bosutinib Onkogen:

• 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 decrease the effectiveness of Bosutinib Onkogen:

• 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.

Avoid taking these medicines while taking Bosutinib Onkogen. Tell your doctor if you are taking any of these medicines. Your doctor may change the dose of these medicines, the dose of Bosutinib Onkogen, 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 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.

Be cautious when taking these medicines while taking Bosutinib Onkogen. Tell your doctor if you are taking any of these medicines. Other medicines may also interact with Bosutinib Onkogen.

Bosutinib Onkogen with food and drink

Do not take Bosutinib Onkogen with grapefruit or grapefruit juice, as this may increase the risk of side effects.

Pregnancy, breastfeeding, and fertility

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

Driving and using machines

If you experience dizziness, blurred vision, or unusual tiredness, do not drive or operate machinery until these effects have resolved.

Bosutinib Onkogen contains sodium

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

3. How to take Bosutinib Onkogen

Take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist. Bosutinib Onkogen 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 myelogenous leukemia is 400 mg once daily. The recommended dose for patients whose previous treatment for chronic myelogenous leukemia has not worked or is not suitable is 500 mg once daily. For patients with moderate or severe kidney disease, your doctor may reduce the dose by 100 mg per day for moderate kidney disease and by an additional 100 mg per day for severe kidney disease. Your doctor may adjust the dose using 100 mg tablets based on your condition, response to treatment, and/or possible side effects. Take the tablets once daily with food. Swallow the tablets whole with water.

If you take more Bosutinib Onkogen than you should

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

If you forget to take Bosutinib Onkogen

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

Stopping Bosutinib Onkogen treatment

Do not stop taking Bosutinib Onkogen 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, contact your doctor immediately. If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Bosutinib Onkogen can cause side effects, although not everybody gets them. If you experience any of the following serious side effects, tell your doctor immediately (see also section 2 "Important information before taking Bosutinib Onkogen"): Blood disorders.Tell your doctor immediately if you experience any of the following symptoms: bleeding, fever, or easy bruising (this may indicate a blood or lymphatic system disorder). Liver disorders.Tell your doctor immediately if you experience any of the following symptoms: itching, yellowing of the whites of the eyes or skin, dark urine, or pain or discomfort in the right upper abdomen or fever. Stomach and/or gut disorders.Tell your doctor about stomach pain, heartburn, diarrhea, constipation, nausea, and vomiting. Heart disorders.Tell your doctor about heart disorders, such as abnormal heart rhythms or abnormal EKG findings called "QT interval prolongation", fainting (loss of consciousness), and irregular heartbeat while taking Bosutinib Onkogen. Reactivation of hepatitis B virus infection.Reactivation (flare-up) of hepatitis B virus infection (liver infection) in patients who have had it in the past. Severe skin reactions.Tell your doctor immediately if you experience any of the following symptoms: painful, red, or purple spreading rash, blisters, and/or other skin changes that start to appear on the mucous membranes (e.g., in the mouth and on the lips). Side effects that may occur when taking Bosutinib Onkogen include:

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

• decreased platelet count, red blood cells, and/or neutrophils (a type of white blood cell)
• diarrhea, vomiting, abdominal pain, nausea
• fever, swelling of hands, feet, or face, fatigue, weakness
• respiratory tract infection
• nasopharyngitis
• changes in blood test results to check if Bosutinib Onkogen is affecting your 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 (may affect up to 1 in 10 people):

• low white blood cell count (leukopenia)
• gastritis (inflammation of the stomach), stomach or gut bleeding
• chest pain, pain
• toxic liver damage, abnormal liver function, including liver dysfunction
• pneumonia (lung infection), influenza, bronchitis
• abnormal heart rhythms that can lead to fainting, dizziness, and palpitations
• high blood pressure
• high potassium levels in the blood, low phosphorus levels in the blood, excessive loss of body fluids (dehydration)
• muscle pain
• taste disturbance
• acute kidney failure, kidney failure, kidney dysfunction
• fluid around the heart (pericardial effusion)
• ringing in the ears
• hives, acne
• allergic reaction to sunlight (sensitivity to UV radiation from the sun and other light sources)
• allergic reaction
• high blood pressure in the lungs (pulmonary hypertension)
• acute pancreatitis
• respiratory failure.

Uncommon (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 eruptions
• inflammation of the sac surrounding the heart (pericarditis)
• significant decrease in 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 phosphorus levels and low calcium levels in the blood), which can lead to kidney dysfunction and acute kidney failure - tumor lysis syndrome.

Rare (may affect up to 1 in 1,000 people):

• 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.

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 of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the national reporting system via the contact details listed below. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Bosutinib Onkogen

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 carton after EXP. The expiry date refers to the last day of that 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. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Bosutinib Onkogen contains

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

What Bosutinib Onkogen looks like and contents of the pack

Bosutinib Onkogen, 100 mg, coated tablets are yellow, oval, biconvex tablets with "C18" engraved on one side. Bosutinib Onkogen, 100 mg is available in blisters containing 28 coated tablets. Bosutinib Onkogen, 100 mg is available in perforated unit-dose blisters containing 28 x 1 coated tablet. Bosutinib Onkogen, 500 mg, coated tablets are pink, oval, biconvex tablets with "C20" engraved on one side. Bosutinib Onkogen, 500 mg is available in blisters containing 28 coated tablets. Bosutinib Onkogen, 500 mg is available in perforated unit-dose blisters containing 28 x 1 coated tablet. Not all pack sizes may be marketed.

Marketing Authorisation Holder

Onkogen Kft. Bécsi Road 77-79 1037 Budapest Hungary Email: vigilance@onkogen.hu

Manufacturer

Coripharma ehf. Reykjavíkurvegur 78-80 220 Hafnarfjörður Iceland

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

Croatia: Bosutinib Onkogen 100 mg, 150 mg film-coated tablets Iceland: Bosutinib Onkogen Poland: Bosutinib Onkogen Hungary: Bosutinib Onkogen 100 mg, 150 mg film tablet

Date of last revision of the leaflet: