Bosutinib onkogen

Package leaflet: Information for the user

Bosutinib Onkogen, 100 mg, film-coated tablets
Bosutinib Onkogen, 500 mg, film-coated tablets
Bosutinibum
Please 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 personally. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

1. What Bosutinib Onkogen is and what it is used for
2. What you need to know before taking 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 Bosutinib Onkogen is and what it is used for

Bosutinib Onkogen contains the active substance bosutinib. This medicine is used to treat adult patients with a type of leukaemia called Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML), either in those who have just been diagnosed or in those in whom previous treatments for chronic myeloid leukaemia have failed or were unsuitable.
Philadelphia chromosome-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 Onkogen works or why this medicine has been prescribed for you, ask your doctor.

2. Important information before using Bosutinib Onkogen

When not to use Bosutinib Onkogen

• 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 the doctor that they have impaired liver function and the liver is not working properly.

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

• if the patient has or has had liver disease. Inform the doctor about any previous liver conditions, including hepatitis (infection or inflammatory condition) of the liver, regardless of type, as well as any previous occurrence of the following liver-related symptoms: itching, yellowing of the whites of the eyes or skin, dark-coloured urine, or pain or discomfort in the upper right part of the abdomen. Before

starting treatment with Bosutinib Onkogen and during the first 3 months of treatment with
Bosutinib Onkogen, and in clinically indicated situations, 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 the normal state, increased frequency of vomiting episodes, presence of blood in vomit, stools (defecations), or urine, or presence of black stools (tarry-black defecations). Ask the doctor whether antiemetic treatment may increase the risk of developing cardiac arrhythmias. Consult the doctor, especially if treatment for nausea and (or) vomiting includes domperidone. Treating nausea or vomiting with such medicines together with Bosutinib Onkogen may increase the risk of serious cardiac arrhythmias.
• if the patient has bleeding. Inform the doctor if any symptoms such as abnormal bleeding or bruising occur in the absence of injury.
• if the patient has an infection. Inform the doctor if any of the following symptoms occur: fever, problems with urination (e.g. burning sensation), new cough, or sore throat.
• if the patient develops fluid retention. Inform the doctor if any of the following symptoms of fluid retention occur during treatment with Bosutinib Onkogen: 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 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 interval 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 Onkogen, 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 increased frequency of urination and production of larger amounts of pale-coloured urine, as well as decreased frequency of urination and production of 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 Onkogen may cause reactivation of hepatitis B virus, 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 if abdominal pain or discomfort in this area occurs.
• 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 to appear on 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 disease, the body may be unable to eliminate all components from dying tumour cells. This complication, known as tumour lysis syndrome, may lead to kidney failure and heart problems within 48 hours after the first dose of Bosutinib Onkogen. 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 be more sensitive to sunlight or UV radiation. It is important to cover skin areas exposed to sunlight and to use sunscreen with a high sun protection factor (SPF).
Children and adolescents
Bosutinib Onkogen 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 Onkogen and other medicines
Inform the doctor or pharmacist about all medicines currently or recently taken, as well as any medicines the patient plans to take, including over-the-counter medicines, vitamins, and herbal remedies. Some medicines may affect bosutinib concentrations in the patient's body. Inform the doctor about taking medicines containing the following active substances:

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

• 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 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 a type of lung cancer called non-small cell lung cancer.

The following active substances may reduce 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 (an herbal remedy available without prescription) used to treat depression,
• efavirenz and etravirine used to treat HIV/AIDS viral infections,
• modafinil used to treat certain types of sleep disorders.

Avoid using these medicines during treatment with Bosutinib Onkogen. Inform the doctor if any of these medicines are being taken. The doctor may adjust the doses of these medicines, adjust the dose of Bosutinib Onkogen, 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 Onkogen. Inform the doctor if any of these medicines are being taken.
Other medicines not listed above 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 adverse effects.
Pregnancy, breastfeeding, and fertility
Bosutinib Onkogen may harm the unborn child; therefore, it should not be taken during pregnancy unless considered necessary. If the patient is pregnant or if there is a possibility of becoming pregnant, consult the doctor before taking Bosutinib Onkogen.
Women taking Bosutinib Onkogen 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 Onkogen.
If the patient is breastfeeding, inform the doctor. Breastfeeding should not be continued during treatment with Bosutinib Onkogen, 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 subside.
Bosutinib Onkogen contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".
3. How to take Bosutinib Onkogen
This medicine should always be taken exactly as prescribed by the doctor. If in doubt, consult the doctor or pharmacist.
Bosutinib Onkogen will be prescribed only by a doctor experienced in medicines used to treat leukaemia.
Dosage and method of administration
The recommended dose for patients with newly diagnosed chronic myeloid leukaemia is 400 mg once daily. The recommended dose for patients in whom previous treatment for chronic myeloid leukaemia has failed or was inappropriate is 500 mg once daily. In patients with moderate or severe kidney disease, the doctor will reduce the dose by 100 mg daily for moderate kidney disease and by an additional 100 mg daily for severe kidney disease.
The doctor may adjust the dose using 100 mg tablets, depending on the patient's condition, response to treatment, and (or) occurrence of possible adverse effects. The tablets should be taken once daily with food. Swallow the tablets whole with water.
Taking more Bosutinib Onkogen than recommended
If too many tablets of Bosutinib Onkogen or a higher dose than recommended is taken by accident, consult a doctor immediately. If possible, show the doctor the medicine packaging or this leaflet. The patient may require medical care.
Missing a dose of Bosutinib Onkogen
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 dose.
Stopping treatment with Bosutinib Onkogen
Do not stop taking Bosutinib Onkogen unless instructed by the doctor. If the patient is unable to take the medicine as directed or believes they no longer need it, they should contact the doctor immediately.
If further doubts arise regarding the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody will experience them.
If any of the serious adverse reactions listed below occur,
you should contact your doctor immediately (see also section 2 "Important information before taking
Bosutinib Onkogen"):
Blood disorders. You must immediately tell 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 function disorders. You must immediately tell your doctor if you experience any of the following symptoms: itching, yellowing of the whites of the eyes or skin, dark urine, pain or discomfort in the upper right part of the abdomen, or fever.
Stomach and (or) intestinal disorders. You should tell your doctor if you experience stomach pain, heartburn, diarrhoea, constipation, nausea, or vomiting.
Heart conditions. You should tell your doctor about any heart problems, such as abnormal electrical signals called "QT prolongation", fainting (loss of consciousness), or irregular heartbeat while taking Bosutinib Onkogen.
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. You should immediately tell your doctor if you experience 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 and lips).

Adverse reactions associated with the use of Bosutinib Onkogen may include:
Very common (may affect more than 1 in 10 people):

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

Common (may affect 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 liver dysfunction
• 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
• presence of fluid around the heart (pericardial effusion)
• tinnitus
• urticaria, 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 (may affect 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 surrounding the heart (pericarditis)
• marked decrease in granulocytes (a type of white blood cell)
• 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 levels of potassium, uric acid and phosphate, and low calcium levels in the blood), which may lead to kidney dysfunction and acute kidney failure – tumour lysis syndrome.

Frequency not known (frequency cannot be estimated from the 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 you experience any adverse effects, including any not listed in this leaflet, you should inform your doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products, 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
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 Onkogen

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister pack and the cardboard
carton after: EXP. The expiry date refers to the last day of the stated month.
No special storage instructions apply for this medicine.
Do not use this medicine if the packaging is damaged or shows signs of tampering.
Medicines must 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 film-coated tablets are available in different strengths.
  Bosutinib Onkogen 100 mg: each film-coated tablet contains 100 mg of bosutinib.
  Bosutinib Onkogen 500 mg: each film-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) – for Bosutinib Onkogen 100 mg, and red iron oxide (E 172) – for Bosutinib Onkogen 500 mg.

What Bosutinib Onkogen looks like and contents of the pack
Bosutinib Onkogen 100 mg film-coated tablets are yellow, oval-shaped, biconvex tablets with the imprint “C18” on one side.
Bosutinib Onkogen 100 mg is available in blisters containing 28 film-coated tablets.
Bosutinib Onkogen 100 mg is also available in perforated unit-dose blister packs containing 28 x 1 film-coated tablet.
Bosutinib Onkogen 500 mg film-coated tablets are pink, oval-shaped, biconvex tablets with the imprint “C20” on one side.
Bosutinib Onkogen 500 mg is available in blisters containing 28 film-coated tablets.
Bosutinib Onkogen 500 mg is also available in perforated unit-dose blister packs containing 28 x 1 film-coated tablet.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Onkogen Kft.
Bécsi Road 77-79
1037 Budapest
Hungary
Email: [email protected]

Manufacturer
Coripharma ehf.
Reykjavíkurvegur 78-80
220 Hafnarfjörður
Iceland

This medicinal product is authorised in the European Economic Area (EEA) member states under the following names:
Croatia: Bosutinib Onkogen 100 mg, 150 mg filmom obložene tablete
Iceland: Bosutinib Onkogen
Poland: Bosutinib Onkogen
Hungary: Bosutinib Onkogen 100 mg, 150 mg filmtabletta