• 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. This includes any possible side effects not listed in this leaflet.
  See section 4.

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

• if you are allergic to bosutinib or any of the other ingredients of this medicine (listed in section 6).
• if your doctor has told you that your liver has been damaged and is not working normally.

Talk to your doctor, pharmacist or nurse before taking Bosutinib if you:

• have, or have had in the past, liver problems. Tell your doctor if you have a history of liver problems including hepatitis (liver infection or inflammation) of any kind, or a history of any of the following signs and symptoms of liver problems: itching, yellow eyes or skin, dark urine, and pain or discomfort in the right upper stomach area. Your doctor should do blood tests to check your liver function prior to your starting treatment with Bosutinib and for the first 3 months of treatment with Bosutinib, and as clinically indicated
• have diarrhoea and vomiting. Tell your doctor if you develop any of the following signs and symptoms: an increase in the number of stools (bowel movements) per day over normal, an increase in episodes of vomiting, blood in your vomit, stools (bowel movements) or urine, or have black stools (tarry black bowel movements). You should ask your doctor if use of your treatment for vomiting may result in a greater risk of heart arrhythmias. In particular, you should ask your doctor if you want to use a medicine containing domperidone for the treatment of nausea and/or vomiting. Treatment of nausea or vomiting with such medicines together with Bosutinib may result in a greater risk of dangerous heart arrhythmias.
• suffer from bleeding problems. Tell your doctor if you develop any of the following signs and symptoms such as abnormal bleeding or bruising without having an injury.
• have an infection. Tell your doctor if you develop any of the following signs and symptoms such as fever, problems with urine such as burning on urination, a new cough, or a new sore throat.
• have fluid retention. Tell your doctor if you develop any of the following signs and symptoms of fluid retention during Bosutinib treatment such as swelling of the ankles, feet or legs; difficulty breathing chest pain or a cough (these may be signs of fluid retention in the lungs or chest).
• have heart problems. Tell your doctor if you have a heart disorder, such as arrhythmias or an abnormal electrical signal called “prolongation of the QT interval”. This is always important, but especially if you are experiencing frequent or prolonged diarrhoea as described above. If you faint (loss of consciousness) or have an irregular heartbeat while taking Bosutinib, tell your doctor immediately, as this may be a sign of a serious heart condition.
• have been told that you have problems with your kidneys. Tell your doctor if you are urinating more frequently and producing larger amounts of urine with a pale colour or if you are urinating less frequently and producing smaller amounts of urine with a dark colour. Also tell your doctor if you are losing weight or have experienced swelling of your feet, ankles, legs, hands or face.
• have ever had or might now have a hepatitis B infection. This is because Bosutinib could cause hepatitis B to become active again, which can be fatal in some cases. Patients will be carefully checked by their doctor for signs of this infection before treatment is started.
• have or have had pancreas problems. Tell your doctor if you develop abdominal pain or discomfort.
• have any of these symptoms: serious skin rashes. Tell your doctor if you develop any of the following signs and symptoms of painful red or purplish rash that spreads and blisters and/or other lesions begin to appear in the mucous membrane (e.g., mouth and lips).
• notice any of these symptoms: pain in your side, blood in your urine or reduced amount of urine. When your disease is very severe, your body may not be able to clear all the waste products from the dying cancer cells. This is called tumour lysis syndrome and can cause kidney failure and heart problems within 48 hours of the first dose of Bosutinib. Your doctor will be aware of this and may ensure you are adequately hydrated and give you other medicines to help prevent it.

You may become more sensitive to the sun or UV rays while taking bosutinib. It is important to cover sunlight-exposed areas of skin and use sunscreen with high sun protection factor (SPF).

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

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription, vitamins, and herbal medicines.

Some medicines can affect the levels of bosutinib in your body. You should inform your doctor if you are taking medicines containing active substances such as those listed below:

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

• 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 (feeling sick) 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:

• rifampicin, used to treat tuberculosis.
• phenytoin and carbamazepine, used to treat epilepsy.
• bosentan, used to lower high blood pressure in the lungs (pulmonary artery hypertension).
• nafcillin, an antibiotic used to treat bacterial infections.
• St. John’s Wort (a herbal preparation obtained without a prescription), used to treat depression.
• efavirenz and etravirine, used to treat HIV infections/AIDS.
• modafinil, used to treat certain types of sleep disorders.

These medicines should be avoided during your treatment with Bosutinib. If you are taking any of them, tell your doctor. Your doctor may change the dose of these medicines, change the dose of Bosutinib, or switch you to a different medicine

The following active substances may affect the heart rhythm:

• amiodarone, disopyramide, procainamide, quinidine and sotalol used to treat heart disorder.
• chloroquine, halofantrine used to treat malaria.
• clarithromycin and moxifloxacin antibiotics used to treat bacterial infections.
• haloperidol, used to treat psychotic disease 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 your treatment with Bosutinib. If you are taking any of them, tell your doctor.

The medicines listed here may not be the only ones that could interact with Bosutinib.

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

Bosutinib is not to be used during pregnancy, unless clearly necessary, because Bosutinib could harm an unborn baby. Ask your doctor for advice before taking Bosutinib if you are pregnant or might become pregnant.

Women taking Bosutinib will be advised to use effective contraception during treatment and for at least 1 month after the last dose. Vomiting or diarrhoea may reduce the effectiveness of oral contraceptives.

There is a risk that treatment with Bosutinib will lead to decreased fertility and you may wish to seek advice about sperm storage before the treatment starts.

If you are breast-feeding, tell your doctor. Do not breast-feed during treatment with Bosutinib as it could harm your baby.

If you experience dizziness, have blurred vision or feel unusually tired, do not drive or operate machines until these side effects have gone away.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

The recommended dose is 400 mg once daily for patients with newly-diagnosed CML. The recommended dose is 500 mg once daily for patients whose previous medicines to treat CML have either not worked or are not suitable. In the event that you have moderate or severe kidney problems, your doctor will reduce your dose by 100 mg once daily for moderate kidney problems and by an additional 100 mg once daily for severe kidney problems. Your doctor may adjust the dose using the 100 mg tablets depending upon your medical conditions, upon your response to treatment and/or on any side effect you may experience. Take the tablet(s) once a day with food. Swallow the tablet(s) whole with water.

If you accidentally take too many Bosutinib tablets or a higher dose than you need, contact a doctor for advice right away. If possible, show the doctor the pack, or this leaflet. You may require medical attention.

If a dose is missed by less than 12 hours, take your recommended dose. If a dose is missed by more than 12 hours, take your next dose at your regular time on the following day.

Do not take a double dose to make up for the forgotten tablets.

Do not stop taking Bosutinib unless your doctor tells you to do so. If you are not able to take the medicine as your doctor prescribed or you feel you do not need it anymore, contact your doctor right away.

If you get 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 via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is bosutinib. Each film-coated tablet contains 100 mg, 400 mg or 500 mg bosutinib.
• The other ingredients are: cellulose microcrystalline (E460), croscarmellose sodium (E468), silica, colloidal anhydrous, magnesium stearate.
  The film-coating contains poly(vinyl alcohol) (E1203), macrogols, talc (E553b), titanium dioxide (E171), iron oxide yellow (E172 Bosutinib 100 mg and 400 mg), Iron oxide red (E172 Bosutinib 400 mg and 500 mg).

Bosutinib 100 mg film-coated tablets are yellow, oval (width: 5.6 mm; length:10.7 mm) biconvex, debossed with “C18” on one side.

Bosutinib 400 mg film-coated tablets are orange, oval (width: 9.0 mm; length: 17.0 mm) biconvex, debossed with “C19” on one side.

Bosutinib 500 mg film-coated tablets are pink, oval (width: 9.7 mm; length: 18.3 mm) biconvex, debossed with “C20” on one side.

The tablets are packaged in Alu/PVC/Alu/OPA blister packs or Alu/PVC/Alu/OPA perforated unit dose blister packs.

Pack sizes: 28 or 112 tablets and 28 x 1 or 112 x 1 tablets.

Not all pack sizes may be marketed.

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