Bosutinib Teva

Package leaflet: Information for the user

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

bosutinib
Generic medicine
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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

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

Bosutinib Teva contains the active substance bosutinib. It is used to treat adult patients with a type of leukaemia called Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML), either at the time of diagnosis or in patients for whom previous treatments for chronic myeloid leukaemia have not worked or were not suitable. Philadelphia chromosome-positive chronic myeloid leukaemia is a form of blood cancer that causes the body to produce an excessive number of a specific type of white blood cells called granulocytes.
If you have any questions about how Bosutinib Teva works or why this medicine has been prescribed for you, please consult your doctor.

2. What you should know before taking Bosutinib Teva

Do not take Bosutinib Teva

• 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 liver damage and that your liver is not functioning normally.

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

• if you have or have previously had liver problems. Inform your doctor if you have previously had liver problems, including hepatitis (liver infection or inflammation) of any kind, or if you have previously experienced any of the following signs and symptoms of liver problems: itching, yellowing of the skin or eyes, dark urine, or pain or discomfort in the upper right part of the abdomen. Your doctor must perform blood tests to monitor liver function before starting treatment with Bosutinib Teva, during the first 3 months of treatment with Bosutinib Teva, and whenever clinically indicated.

• if you have diarrhea or vomiting. Inform your doctor if you develop any of the following signs and symptoms: an increase in the number of bowel movements (stools) per day beyond normal, increased episodes of vomiting, blood in vomit, stools (bowel movements), or urine, or black stools (tarry bowel movements). You should ask your doctor whether treatment for vomiting may increase the risk of developing cardiac arrhythmias. In particular, consult your doctor before taking any medicine containing domperidone to treat nausea and/or vomiting. Treating nausea or vomiting with this type of medicine while taking Bosutinib Teva may increase the risk of dangerous cardiac arrhythmias.

• if you have bleeding problems. Inform your doctor if you develop any of the following signs and symptoms, such as abnormal bleeding or bruising without injury.

• if you have an infection. Inform your doctor if you develop any of the following signs and symptoms, such as fever, problems with urination—for example, a burning sensation when urinating—or new onset of cough or sore throat.

• if you have fluid retention. Inform your doctor if you develop any of the following signs and symptoms of fluid retention during treatment with Bosutinib Teva, such as 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 problems. Inform your doctor if you have a heart condition, such as heart failure or reduced blood flow to the heart, which may lead to a heart attack. Seek immediate medical help if you experience shortness of breath, 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 always important, but especially so if you experience frequent or prolonged diarrhea, as described above. If you faint (lose consciousness) or have an irregular heartbeat while taking Bosutinib Teva, inform your doctor immediately, as this may be a sign of a serious heart condition.

• if you have been told you have kidney problems. Inform your doctor if you urinate more frequently and produce larger amounts of light-colored urine, or if you urinate less frequently and produce smaller amounts of dark-colored urine. Also inform your doctor if you are losing weight or have developed swelling in your feet, ankles, legs, hands, or face.

• if you have had or may currently have hepatitis B infection. This is because Bosutinib Teva may cause reactivation of hepatitis B, which in some cases can be fatal. Your doctor will carefully monitor you for signs of this infection before starting treatment.

• if you have or have previously had pancreas problems. Inform your doctor if you develop abdominal pain or discomfort.

• if you develop any of these symptoms: severe skin rash. Inform your doctor if you develop any of the following signs or symptoms of a severe skin rash, such as painful, red or purplish rash that spreads progressively, and blisters and/or other lesions starting to appear on mucous membranes (e.g., mouth and lips).

• if you experience any of these symptoms: flank pain, blood in the urine, or reduced urine output. If your disease is very advanced, your body may not be able to eliminate waste products from dead tumor cells. This condition is called tumor lysis syndrome and may lead to kidney failure and heart problems within 48 hours of the first dose of Bosutinib Teva. Your doctor is aware of this risk and may ensure you receive adequate hydration and possibly other medicines to prevent this condition.

Sun/UV protection
While taking bosutinib, you may become more sensitive to sunlight or UV rays. It is important to cover skin areas exposed to sunlight and to use sunscreen creams with a high sun protection factor (SPF).

Children and adolescents
Bosutinib Teva is not recommended for people under 18 years of age. This medicine has not been studied in children and adolescents.

Other medicines and Bosutinib Teva
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any medicines, including over-the-counter medicines, vitamins, and herbal supplements.
Some medicines may affect the levels of Bosutinib Teva 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 Bosutinib Teva side effects:

• 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 leukemia.
• 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 Teva:

• 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, a 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 Teva. If you are taking any of these medicines, inform your doctor. Your doctor may adjust the dose of these medicines or of Bosutinib Teva, 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, 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 taken with caution during treatment with Bosutinib Teva. If you are taking any of these medicines, inform your doctor.
The medicines listed here may not be the only ones that interact with Bosutinib Teva.

Bosutinib Teva with food and drinks
Do not take Bosutinib Teva with grapefruit or grapefruit juice, as the risk of side effects may increase.

Pregnancy, breastfeeding, and fertility
Bosutinib Teva must not be used during pregnancy unless considered necessary, as it may harm the unborn baby. Ask your doctor for advice before taking Bosutinib Teva if you are pregnant or could become pregnant.
Women taking Bosutinib Teva will be advised to use an effective method of contraception during treatment and for at least 1 month after the last dose. Vomiting or diarrhea may reduce the effectiveness of oral contraceptives.
Treatment with Bosutinib Teva may reduce male fertility; therefore, you may wish to consider sperm preservation before starting therapy.
If you are breastfeeding, inform your doctor. Do not breastfeed during treatment with Bosutinib Teva, as it may harm the baby.

Driving and using machines
If you experience dizziness, blurred vision, or feel unusually tired, do not drive or operate machinery until these side effects have resolved.

3. How to take Bosutinib Teva

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
Bosutinib Teva will be prescribed only by a doctor experienced in medicines for the treatment of leukaemia.

Dosage and method of administration
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 medicines for the treatment of chronic myeloid leukaemia have not worked or are not suitable. If you have moderate or severe renal problems, your doctor will reduce the dose by 100 mg once daily for moderate renal impairment and by a further 100 mg once daily for severe renal impairment. Depending on your medical condition, your response to treatment and/or any side effects you may experience, your doctor may adjust the dose using the 100 mg tablets. Take the tablet(s) once daily with food. Swallow the tablet(s) whole with some water.

If you take more Bosutinib Teva than you should
If you accidentally take too many Bosutinib Teva tablets or a higher dose than required, contact a doctor immediately for advice. If possible, show the doctor the pack or this leaflet. You may require medical treatment.

If you forget to take Bosutinib Teva
If less than 12 hours have passed since the scheduled dose 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 a forgotten tablet.

If you stop taking Bosutinib Teva
Do not stop taking Bosutinib Teva unless your doctor tells you to. If you are unable to take the medicine as prescribed or if you feel you no longer need it, contact your doctor immediately.

If you have any questions about how to use 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.
You must contact your doctor immediately if you experience any of the serious side effects (see also section 2 “What you need to know before taking Bosutinib Teva”):

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

Liver problems. Inform your doctor immediately if you have any of the following symptoms: itching, yellowing of the skin or eyes, dark urine, pain or discomfort in the upper right side of the stomach, or fever.

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

Heart problems. Inform your doctor if you have a heart condition, such as heart failure, reduced blood flow to the heart, an abnormal electrical signal known as “QT interval prolongation”, or if you faint (lose consciousness) or have an irregular heartbeat while taking Bosutinib Teva.

Hepatitis B reactivation. Recurrence (reactivation) of hepatitis B infection if you have previously had hepatitis B (a liver infection).

Severe skin reactions. Seek immediate medical attention if you experience any of the following symptoms: painful red or purplish rash that spreads progressively, and blisters and/or other lesions starting to appear on mucous membranes (e.g. mouth and lips).

Side effects of Bosutinib Teva may include:

Very common side effects (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, stomach pain, nausea
• fever, swelling of the hands, feet or face, fatigue, weakness
• respiratory tract infection
• nasopharyngitis
• changes in blood tests indicating that Bosutinib Teva is affecting the liver and/or pancreas, kidneys
• decreased appetite
• joint pain, back pain
• headache
• rash, which may be itchy and/or widespread
• cough
• shortness of breath
• feeling of instability (dizziness)
• fluid in the lungs (pleural effusion)
• itching

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

• low white blood cell count (leucopenia)
• stomach irritation (gastritis), bleeding from the stomach or intestine
• chest pain, pain
• toxic liver damage, abnormal liver function, including liver disorders
• lung infection (pneumonia), influenza, bronchitis
• when the heart does not pump blood properly (heart failure)
• heart rhythm disorder that may lead 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 (dysgeusia)
• acute kidney failure, kidney failure, impaired kidney function
• fluid around the heart (pericardial effusion)
• ringing in the ears (tinnitus)
• urticaria, acne
• photosensitivity reaction (sensitivity to UV sunlight and other light sources)
• allergic reaction
• abnormally high blood pressure in the arteries of the lungs (pulmonary hypertension)
• acute inflammation of the pancreas (acute pancreatitis)
• respiratory failure

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

• fever associated with low red blood cell count (febrile neutropenia)
• liver damage
• potentially life-threatening allergic reaction (anaphylactic shock)
• abnormal accumulation of fluid in the lungs (acute pulmonary edema)
• rash
• inflammation of the membrane lining the heart (pericarditis)
• marked reduction in the number of granulocytes (a type of white blood cell)
• 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 phosphate, and low calcium levels in the blood) which may lead to changes in kidney function and acute kidney failure – (tumour lysis syndrome (TLS))
• inflammation of blood vessels in the skin which may cause rash or bruising (cutaneous vasculitis)

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

• severe skin disorder (Stevens-Johnson syndrome, toxic epidermal necrolysis) due to an allergic reaction, exfoliative rash (scaly skin, exfoliation)
• interstitial lung disease (a disease causing scarring in the lungs): signs include cough, difficulty breathing, painful breathing

Reporting of side effects
If you experience any side effect, 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 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 Teva

• Keep this 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 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 any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Bosutinib Teva contains

• The active substance is bosutinib. Bosutinib Teva film-coated tablets are available in different strengths.
  Bosutinib Teva 100 mg: each film-coated tablet contains 100 mg of bosutinib (as dihydrate).
  Bosutinib Teva 400 mg: each film-coated tablet contains 400 mg of bosutinib (as dihydrate).
  Bosutinib Teva 500 mg: each film-coated tablet contains 500 mg of bosutinib (as dihydrate).
• The other components are:
• Tablet core: microcrystalline cellulose, crospovidone, poloxamer 188, povidone, magnesium stearate.
  The film coating of the 100 mg tablet contains: hypromellose, titanium dioxide (E 171), macrogol 3350, iron oxide yellow (E 172).
  The film coating of the 400 mg tablet contains: hypromellose, titanium dioxide (E 171), macrogol 6000, iron oxide yellow (E 172), iron oxide red (E 172).
  The film coating of the 500 mg tablet contains: hypromellose, titanium dioxide (E 171), macrogol 400, talc, iron oxide red (E 172).

Description of the appearance of Bosutinib Teva and contents of the pack
Bosutinib Teva 100 mg film-coated tablets are biconvex, yellow, oval, film-coated tablets approximately 11 mm x 5 mm in size, marked with "100" on one side and "B" on the other side.
Bosutinib Teva 100 mg is available in PVC/Aclar-aluminum blisters containing 28, 30 or 112 film-coated tablets, or in unit-dose divisible PVC/Aclar-aluminum blisters containing 28x1, 30x1 or 112x1 film-coated tablets.
Bosutinib Teva 400 mg film-coated tablets are biconvex, orange, oval, film-coated tablets approximately 16 mm x 9 mm in size, marked with "400" on one side and "B" on the other side.
Bosutinib Teva 400 mg is available in PVC/Aclar-aluminum blisters containing 28 or 30 film-coated tablets, or in unit-dose divisible PVC/Aclar-aluminum blisters containing 28x1 or 30x1 film-coated tablets.
Bosutinib Teva 500 mg film-coated tablets are biconvex, red, oval, film-coated tablets approximately 18 mm x 9 mm in size, marked with "500" on one side and "B" on the other side.
Bosutinib Teva 500 mg is available in PVC/Aclar-aluminum blisters containing 28 or 30 film-coated tablets, or in unit-dose divisible PVC/Aclar-aluminum blisters containing 28x1 or 30x1 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Teva Italia S.r.l. - Piazzale Luigi Cadorna, 4 - 20123 Milano

Manufacturer
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
PLA3000 Paola, Malta

This medicinal product is authorized in the European Economic Area countries under the following names:
Austria: Bosutinib Teva 100 mg Filmtabletten, Bosutinib Teva 400 mg Filmtabletten, Bosutinib Teva 500 mg Filmtabletten
Belgium: Bosutinib Teva 100 mg filmomhulde tabletten/comprimés pelliculés/Filmtabletten, Bosutinib Teva 400 mg filmomhulde tabletten/comprimés pelliculés/Filmtabletten, Bosutinib Teva 500 mg filmomhulde tabletten/comprimés pelliculés/Filmtabletten
Bulgaria: Босутиниб Тева 100 mg филмирани таблетки, Bosutinib Teva 100 mg film-coated tablets, Босутиниб Тева 500 mg филмирани таблетки, Bosutinib Teva 500 mg film-coated tablets
Czech Republic: Bosutinib Teva
Germany: Bosutinib-ratiopharm 100 mg Filmtabletten, Bosutinib-ratiopharm 400 mg Filmtabletten, Bosutinib-ratiopharm 500 mg Filmtabletten
Denmark: Bosutinib Teva
France: BOSUTINIB TEVA 100 mg, comprimé pelliculé, BOSUTINIB TEVA 400 mg, comprimé pelliculé, BOSUTINIB TEVA 500 mg, comprimé pelliculé
Croatia: Bosutinib Teva 100 mg, 400 mg, 500 mg filmom obložene tablete
Iceland: Bosutinib Teva
Italy: Bosutinib Teva
Luxembourg: Bosutinib Teva 100 mg comprimés pelliculés, Bosutinib Teva 400 mg comprimés pelliculés, Bosutinib Teva 500 mg comprimés pelliculés
Netherlands: Bosutinib Teva 100 mg, filmomhulde tabletten, Bosutinib Teva 400 mg, filmomhulde tabletten, Bosutinib Teva 500 mg, filmomhulde tabletten
Norway: Bosutinib Teva
Portugal: Bosutinib Teva
Romania: Bosutinib Teva 100 mg, 400 mg, 500 mg comprimate filmate
Sweden: Bosutinib Teva