Bosutinib 100 mg, 400 mg and 500 mg Film-coated Tablets – patient leaflet, side effects, dosage

1. What Bosutinib Film-coated Tablets are and what they are used for

Bosutinib Film-coated Tablets contain the active substance bosutinib. It is used to treat adult and paediatric patients aged 6 years and older who have a type of leukaemia called chronic phase (CP) Philadelphia chromosome-positive (Ph-positive) Chronic Myeloid Leukaemia (CML) and are newly-diagnosed or for whom previous medicines to treat CML have either not worked or are not suitable. It is also used to treat adult patients with accelerated phase (AP) and blast phase (BP) Ph+ CML for whom previous medicines to treat CML have not worked or are not suitable.

In patients with Ph-positive CML a change in DNA (genetic material) triggers a signal that tells the body to produce too many of a specific type of white blood cell called granulocytes. Bosutinib blocks this signal and therefore stops the production of these cells.

If you have any questions about how Bosutinib Film-coated Tablets work or why this medicine has been prescribed for you, ask your doctor.

2. What you need to know before you take Bosutinib Film-coated Tablets

Do not take Bosutinib Film-coated Tablets if:

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

Warnings and precautions

Talk to your doctor or pharmacist 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 (see section 4 “Possible side effects”) because Bosutinib may affect your liver function. 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 this medicine and as clinically indicated.
• have diarrhoea and vomiting. Tell your doctor if you develop any signs and symptoms of stomach or intestinal problems or of the following: 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 signs and symptoms of blood problem (see section 4 “Possible Side Effects”), because Bosutinib reduces the capability of your body to stop bleeding. During the first month, your doctor will perform weekly and then monthly complete blood counts for you. Your doctor may also withhold temporarily, dose reduce or discontinue Bosutinib (see section 3 “How to take Bosutinib”).

• 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 because Bosutinib reduces the capability of your body to defend from infections.

  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). Your doctor will monitor you for fluid retention and will manage your symptoms.

• have heart problems. Tell your doctor if you have a heart disorder, such as heart failure and decreased blood flow to the heart which can lead to heart attack. Get medical help right away if you get shortness of breath, weight gain, chest pain, or swelling in your hands, ankles or feet.
• have been told you have abnormal heart rhythm. Tell your doctor if you have 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 (see section 2 “What do you need to know before you take Bosutinib”). Your doctor will perform an electrocardiogram (ECG) before you start therapy. Your doctor will do a blood test prior to and during therapy and if you have low potassium or magnesium, your doctor will provide a treatment to correct the low blood levels.

• 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. Your doctor will assess how your kidneys are functioning before treatment and will closely monitor how your kidneys are functioning during the course of treatment with bosutinib.

  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. Your doctor will test you for this infection before starting treatment. If you have this infection, your doctor will monitor you closely for signs and symptoms of the infection throughout therapy and several months after you have stopped therapy.

• have or have had pancreas problems. Tell your doctor if you develop abdominal pain or discomfort. If you have abdominal pain and your blood tests show high levels of lipase, an enzyme that helps your body break down fats in food, then your doctor may interrupt your treatment and perform tests to rule out problems with your pancreas.
• 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). If you develop a severe skin reaction during treatment, your doctor will permanently discontinue treatment.

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 this medicine. Your doctor will be aware of this and may ensure you are adequately hydrated and give you other medicines to help prevent it. Your doctor will perform a blood test to check for high uric acid levels and your doctor will provide a treatment to correct the high levels prior to starting therapy.

Sun/UV protection

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).

Patients of Asian origin

If you are of Asian origin, you may have an increased risk of side effects with Bosutinib. Your doctor will closely monitor you for serious side effects especially when increasing the dose.

Children and adolescents

This medicine is not recommended for people under the age of 6 years. This medicine has not been studied in children below the age of 1 year.

Other medicines and Bosutinib Film-coated Tablets

Tell your doctor or pharmacist 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 Film-coated Tablets:

• 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 Film-coated Tablets:

• 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 Film-coated Tablets. 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.

Acid reducing agents

Proton pump inhibitors (PPIs) should be taken with caution during your treatment with Bosutinib as they may reduce the effectiveness of Bosutinib. Your doctor may consider short acting antacids as an alternative to PPIs and administration times of Bosutinib and antacids should be separated (i.e. take Bosutinib in the morning and antacids in the evening) whenever possible.

The medicines listed here may not be the only ones that could interact with Bosutinib, if you are not sure if the above applies to you or your child, ask your doctor.

Bosutinib Film-coated Tablets with food and drink

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

Pregnancy, breast-feeding and fertility

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

Women taking Bosutinib Film-coated Tablets 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 this medicine 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 this medicine as it could harm your baby.

Driving and using machines

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

3. How to take Bosutinib Film-coated Tablets

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

This medicine will only be prescribed to you by a doctor with experience in medicines to treat leukaemia.

Dose and method of administration

Adults

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.

Children and adolescents (6 years of age and older)

The recommended dose is 300 mg/m2 body surface area once daily for newly-diagnosed paediatric patients. The recommended dose is 400 mg/m2 body surface area once daily for resistant or intolerant paediatric patients.

Dose recommendations are provided in the following table. As appropriate, for the recommended dose you may combine different strengths of bosutinib film-coated tablets and/or hard capsules (see Package Leaflet for hard capsules).

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

* maximum starting dose (corresponding to maximum starting dose in adult indication)

In the event you are not able to tolerate the recommended dose or are not responding to Bosutinib correctly, your doctor may adjust your dose further.

Take the tablet(s) once a day with food. Swallow the tablet(s) whole with water.

If you take more Bosutinib Film-coated Tablets than you should

If you accidentally take too many Bosutinib Film-coated 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 you forget to take Bosutinib Film-coated Tablets

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.

If you stop taking Bosutinib Film-coated Tablets

Do not stop taking this medicine 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 have any further questions on the use of this medicine ask your doctor or pharmacist.

4. Possible side effects

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

You must immediately contact your doctor if you experience any of those serious side effects (see also section 2 “What you need to know before you take Bosutinib Film-coated Tablets”):

Blood disorders. Tell your doctor right away if you have any of these symptoms: bleeding, fever or easy bruising (you might have blood or lymphatic system disorder).

Liver disorders. Tell your doctor right away if you have any of these symptoms: itching, yellow eyes or skin, dark urine, and pain or discomfort in the right upper stomach area or fever.

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

Heart problems. Tell your doctor if you have a heart disorder, such as an abnormal electrical signal called “prolongation of the QT interval”, or if you faint (loss of consciousness) or have an irregular heartbeat while taking this medicine.

Hepatitis B reactivation. Recurrence (reactivation) of hepatitis B infection when you have had hepatitis B in the past (a liver infection).

Severe skin reactions. Tell your doctor right away if you have any of these symptoms: 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).

Side effects with bosutinib may include:

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

• reduction in the number of platelets (thrombocytopenia), red blood cells (anaemia) and/or neutrophils (type of white blood cells), (neutropenia) which may cause you to have abnormal bleeding, fever, or easy bruising without having an injury (you might have blood or lymphatic system disorder) see section 2 “What do you need to know before you take Bosutinib”).
• diarrhoea, vomiting, stomach pain (abdominal pain), nausea
• fever (pyrexia), swelling of hands, feet or face (oedema), fatigue, weakness
• respiratory tract infection
• nasopharyngitis
• changes in blood test to determine if this medicine is affecting your liver (alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased) and/or pancreas (lipase increased), kidneys (blood creatinine increased).
• decrease of appetite
• joint pain (arthralgia), back pain
• headache
• skin rash, which may be itchy and/or generalised (rash)
• cough
• shortness of breath (dyspnoea).
• feeling of instability (dizziness)
• fluid around the lungs (pleural effusion)

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

• low white blood cells count (leukopenia)
• stomach irritation (gastritis), bleeding from the stomach or intestine (gastrointestinal haemorrhage) which may include blood in your vomit, stools (bowel movements) or urine, or have black stools (tarry black bowel movements) (see section 2 “What do you need to know before you take Bosutinib”).
• chest pain, pain

• toxic damage to the liver (hepatotoxicity), abnormal hepatic function including liver disorder

  (hepatic function abnormal) which may be accompanied with itching, yellow eyes or skin, dark urine, and pain or discomfort in the right upper stomach area or fever (see section 2 “What do you need to know before you take Bosutinib”).

• when the heart does not pump blood as well as it should (heart failure).
• when there is decreased blood flow to the heart (cardiac ischaemia).
• infection of the lung (pneumonia), influenza, bronchitis
• changes in blood test to determine if Bosutinib is affecting your heart (blood creatine phosphokinase increased), liver (blood bilirubin increased, gamma glutamyltransferase (GGT) increased), and/or pancreas (amylase increased).
• defect in cardiac rhythm (electrocardiogram QT prolonged) that predisposes to fainting, dizziness and palpitation
• increase in blood pressure (hypertension).

• high level of potassium in the blood (hyperkalaemia), low level of phosphorus in the blood,

  (hypophosphataemia), excessive loss of body fluid (dehydration)

• pain in the muscles (myalgia).
• alteration of the sense of taste (dysgeusia)
• acute kidney failure, kidney failure (renal failure), kidney impairment (renal impairment).
• fluid around the heart (pericardial effusion)
• ringing in the ears (tinnitus)
• urticaria (hives), acne
• photosensitivity reaction (sensitivity to UV rays from the sun and other light sources)

• allergic reaction (drug hypersensitivity).

  • abnormally high blood pressure in the arteries of the lungs (pulmonary hypertension)
  • acute inflammation of the pancreas (acute pancreatitis)
  • itching.

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

• fever associated with low white blood cell count (febrile neutropenia)
• damage to the liver (liver injury).
• life-threatening allergic reaction (anaphylactic shock)
• abnormal build-up of fluid in the lungs (acute pulmonary oedema)
• skin eruption (drug eruption).
• scaly, peeling rash (exfoliative rash).
• inflammation of the sac-like covering of the heart (pericarditis)
• a marked decrease in the number of granulocytes (a type of white blood cells, granulocytopenia).
• severe skin disorder (erythema multiforme)
• Inflammation of blood vessels in the skin which may result in a rash or bruising (cutaneous vasculitis)
• nausea, shortness of breath, irregular heartbeat, muscular cramps, seizure, clouding of urine and tiredness associated with abnormal laboratory test results (high potassium, uric acid and phosphorous levels and low calcium levels in the blood) that can lead to changes in kidney function and acute renal failure – (Tumour lysis syndrome (TLS)).
• respiratory failure.

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

• severe skin disorder (Stevens-Johnson syndrome, toxic epidermal necrolysis) that may include painful red or purplish rash that spreads and blisters and/or other lesions that begin to appear in the mucous membrane (e.g., mouth and lips) due to an allergic reaction,
• interstitial lung disease (disorders causing scarring in the lungs): signs include cough, difficulty breathing, painful breathing.

Reporting of side effects

If you get any side effects, talk to your doctor or 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 Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

5. How to store Bosutinib Film-coated Tablets

• 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 foil and 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 pack is damaged or shows signs of tampering.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Bosutinib Film-coated Tablets contain

• The active substance is bosutinib. Bosutinib Film-coated Tablets come in different strengths:

  Bosutinib 100 mg: each film-coated tablet contains 100 mg of bosutinib (as dihydrate). Bosutinib 400 mg: each film-coated tablet contains 400 mg of bosutinib (as dihydrate). Bosutinib 500 mg: each film-coated tablet contains 500 mg of bosutinib (as dihydrate).

• The other ingredients are:

  Tablet core: cellulose microcrystalline, crospovidone, poloxamer 188, povidone and magnesium stearate.

  100 mg: Tablet film-coating contains: hypromellose, titanium dioxide (E 171), macrogol 3350 and iron oxide yellow (E 172).

  400 mg: Tablet film-coating contains: hypromellose, titanium dioxide (E 171), macrogol 6000, iron oxide yellow (E 172) and iron oxide red (E 172).

  500 mg: Tablet film-coating contains: hypromellose, titanium dioxide (E 171), macrogol 400, talc and iron oxide red (E 172).

What Bosutinib Film-coated Tablets look like and contents of the pack

• Bosutinib 100 mg Film-coated Tablets are yellow, oval, biconvex, film-coated tablets of size approximately 11 mm x 5 mm, debossed with “100” on one side and “B” on the other side. Available in PVC/Aclar-Aluminium blisters containing 28, 30 or 112 film-coated tablets or in PVC/Aclar-Aluminium perforated unit dose blisters containing 28, 30 or 112 film-coated tablets.
• Bosutinib 400 mg Film-coated Tablets are orange, oval, biconvex, film-coated tablets of size approximately 16 mm x 9 mm, debossed with “400” on one side and “B” on the other side. Available in PVC/Aclar-Aluminium blisters containing 28 or 30 film-coated tablets or in PVC/Aclar-Aluminium perforated unit dose blisters containing 28 or 30 film-coated tablets.
• Bosutinib 500 mg Film-coated Tablets are red, oval, biconvex, film-coated tablets of size approximately 18 mm x 9 mm, debossed with “500” on one side and “B” on the other side. Available in PVC/Aclar-Aluminium blisters containing 28 or 30 film-coated tablets or in PVC/Aclar-Aluminium perforated unit dose blisters containing 28 or 30 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder: Teva UK Limited, Ridings Point, Whistler Drive, Castleford, WF10 5HX, United Kingdom

Manufacturer: Pharmadox Healthcare Ltd, KW20A Kordin Industrial Park, Paola, LA3000, Malta

This leaflet was last revised in May 2026.

PL 00289/2596, PL 00289/2597 and PL 00289/2598