Bosutinib belongs to a family of medications called protein tyrosine kinase inhibitors. It is used to treat adults with certain types of Philadelphia positive chronic myelogenous leukemia (Ph+ CML) in blast crisis (sudden attack), accelerated phase (fast growth), or in chronic phase (long-term illness). Bosutinib works by affecting enzymes that play a role in certain cancer cells to reduce the growth and spread of the cancer cells.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

The usual recommended dose of bosutinib depends on the type of CML you have, as well as if you have received previous treatments. Starting doses range between 400 mg to 500 mg taken by mouth once daily.

Bosutinib should be swallowed whole with water, and taken with a meal. Do not crush or cut the tablets.

Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

It is important that this medication be taken exactly as prescribed by your doctor.

If you miss a dose, and it is less than 12 hours since the missed dose, take the medication with food, as soon as you remember. If it is more than 12 hours since the missed dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.

100 mg 
Each yellow, oval, biconvex, film-coated tablet debossed with "Pfizer" on one side and "100" on the other, contains 103.40 mg of bosutinib monohydrate, equivalent to 100 mg of bosutinib. Nonmedicinal ingredients: microcrystalline cellulose, croscarmellose sodium, poloxamer, povidone, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and iron oxide yellow.

400 mg
Each orange, oval, biconvex, film-coated tablet, debossed "Pfizer" on one side and "400" on the other, contains 413.60 mg of bosutinib monohydrate, equivalent to 400 mg of bosutinib. Nonmedicinal ingredients: microcrystalline cellulose, croscarmellose sodium, poloxamer, povidone, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, iron oxide yellow, and iron oxide red.

500 mg 
Each red, oval, biconvex, film-coated tablet debossed with "Pfizer" on one side and "500" on the other, contains 516.98 mg of bosutinib monohydrate, equivalent to 500 mg of bosutinib. Nonmedicinal ingredients: microcrystalline cellulose, croscarmellose sodium, poloxamer, povidone, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and iron oxide red.

Do not take bosutinib if you:

• are allergic to bosutinib or any ingredients of the medication
• have a history of irregular heartbeat, particularly long QT syndrome
• have reduced liver function
• have untreated low potassium or low magnesium in your blood

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• acne
• changed sense of taste
• cold symptoms (e.g., sore throat, runny nose)
• decreased appetite
• diarrhea
• fatigue
• flu-like symptoms (sudden lack of energy, fever, cough, sore throat)
• headache
• itchy skin
• joint pain
• nausea
• skin rash
• stomach pain or irritation
• vomiting
• weakness

Although most of the side effects listed below don't happen very often, they could lead to serious problems if you do not check seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• abnormal heart rhythms (such as fast or slow heart rate, palpitations), fainting, or seizures
• chest pain
• dizziness
• fever
• generalized pain (back pain, muscle pain)
• increased blood pressure
• shortness of breath
• signs of anemia (low red blood cells; e.g., dizziness, pale skin, unusual tiredness or weakness, shortness of breath)
• signs of bleeding (e.g., bloody nose, blood in urine, coughing blood, bleeding gums, cuts that don't stop bleeding)
• signs of breathing problems (e.g., shortness of breath, troubled breathing, wheezing, or tightness in chest, fast or irregular breathing)
• signs of dehydration (e.g., decreased urine, dry skin, dry and sticky mouth, sleepiness, dizziness, headache, thirst, confusion)
• signs of fluid build-up around the lungs (e.g., chest pain, cough, hiccups, rapid breathing)
• signs of infection (symptoms may include fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness)
• signs of kidney failure (e.g., decreased urine production, swelling, fatigue, abdominal pain)
• signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
• signs of pneumonia (e.g., fever, chills, shortness of breath, cough)
• swelling of the hands, feet, or face
• symptoms of fluid build-up around the heart (e.g., fever, fatigue, muscle aches, shortness of breath, nausea, vomiting, diarrhea, fast or pounding heartbeat, light-headedness)
• symptoms of inflammation of tissue surrounding the heart (pericarditis; e.g., chest pain, cough, fast or irregular heartbeat, shortness of breath, weakness or fatigue)
• symptoms of respiratory failure (e.g., dizziness, trouble breathing, shortness of breath, fast, shallow breathing, wheezing, bluish colouration to the skin and lips from lack of oxygen)
• symptoms of too little phosphorus in the blood (e.g., muscle weakness, fatigue, bone pain, fractures, numbness, confusion)
• symptoms of too much potassium in the body (e.g., muscle fatigue, weakness, difficulty moving, abnormal heart rhythms, nausea)

Stop taking the medication and seek immediate medical attention if any of the following occur:

• signs of a serious allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, or swelling of the face and throat)
• signs of a severe skin reaction such as blistering, peeling, a rash covering a large area of the body, a rash that spreads quickly, or a rash combined with fever or discomfort
• signs of bleeding in the stomach (e.g., bloody, black, or tarry stools, spitting up of blood, vomiting blood or material that looks like coffee grounds)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Abnormal heart rhythms: This medication can cause abnormal heart rhythms. Certain medications (e.g., sotalol, quinidine, thioridazine, chlorpromazine, pimozide, moxifloxacin, mefloquine, pentamidine, arsenic trioxide, tacrolimus) can increase the risk of a type of abnormal heart rhythm called QT prolongation, and should not be used in combination with bosutinib. You are more at risk for this type of abnormal heart rhythm and its complications if you:

• are female
• are older than 65 years of age
• have a family history of sudden cardiac death
• have a history of heart disease or abnormal heart rhythms
• have a slow heart rate
• have congenital prolongation of the QT interval
• have diabetes
• have had a stroke
• have low potassium, magnesium, or calcium levels
• have nutritional deficiencies

If you have heart disease and abnormal heart rhythms, or are taking certain medications (e.g., verapamil, atazanavir), discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Anemia: Bosutinib may cause low levels of red blood cells. If you experience symptoms of reduced red blood cell count (anemia) such as shortness of breath, feeling unusually tired, or pale skin, contact your doctor as soon as possible.

Your doctor will do blood tests regularly to monitor the number of specific types of blood cells, including red blood cells, in your blood.

Birth control: Effective birth control should be practiced while using this medication as this medication may harm the baby if used during pregnancy. Both men and women should use effective birth control (e.g., condoms, birth control pill) during treatment and for at least 4 weeks after treatment is finished. If you or your partner become pregnant while taking this medication, contact your doctor immediately.

Bleeding: Bosutinib may cause a reduced number of platelets in the blood, which can make it difficult to stop cuts from bleeding. If you notice any signs of bleeding, such as frequent nosebleeds, unexplained bruising, or black and tarry stools, notify your doctor as soon as possible. Your doctor will order routine blood tests to make sure potential problems are caught early.

Bone health: People who take bosutinib may be at an increased risk of bone fractures as a result of a decrease in the density and strength of bones. This effect is more likely to occur with people who have osteoporosis or have changes in minerals in the blood or hormones that affect how the body retains calcium. If you have osteoporosis or risk factors for osteoporosis (female, small stature, over age 65, long-term use of corticosteroids or certain other medications), discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Drowsiness/reduced alertness: This medication is not expected to make you drowsy and impair your ability to drive or use machinery. However, it may make some people feel weak. Do not drive or use machinery until you know how this medication affects you.

Dehydration: Severe dehydration can occur with the use of bosutinib. This may be due to severe or persistent diarrhea, vomiting, or decreased fluid intake. Dehydration can lead to kidney failure, if it is severe enough. While you are taking bosutinib, you may be encouraged to drink extra water. Your doctor will do blood tests to check the function of your kidneys.

Fluid retention: This medication can cause serious fluid retention. If you experience unexpected rapid weight gain or swelling in your feet, ankles, lower legs, or hands, contact your doctor immediately. Your doctor will weigh and monitor you regularly for signs of fluid retention while you are taking this medication.

Gastrointestinal bleeding: Bosutinib can cause bleeding in the digestive system. This is very serious and sometimes fatal. If you experience signs of bleeding from the stomach or intestines, such as vomiting blood or material that looks like coffee grounds, or stools that are black and tarry, get immediate medical attention.

Grapefruit juice, star fruit, and pomegranate: Grapefruit and grapefruit juice, star fruit, and pomegranate all affect how bosutinib is removed from the body and may cause too much of the medication to build up in the body. Avoid these foods and juices while you are taking bosutinib.

Heart problems and heart failure: If you are at risk for heart problems such as heart failure (e.g., if you have high blood pressure, diabetes, or coronary artery disease), discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Contact your doctor immediately if you have symptoms of heart failure such as leg swelling, chest pain, or shortness of breath.

Hepatitis B: People who have chronic (long-term) hepatitis B may experience a flare-up of hepatitis B symptoms when they take bosutinib. In severe cases, this can cause liver failure, may necessitate a liver transplant, or may even be fatal. If you have a history of hepatitis B, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Infection: As well as killing cancer cells, bosutinib can reduce the number of cells that fight infection in the body (white blood cells). If possible, avoid contact with people with contagious infections. Tell your doctor immediately if you notice signs of an infection, such as fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness. Your doctor will do blood tests regularly to monitor the number of specific types of blood cells in your blood.

Kidney function: Decreased kidney function or kidney disease may cause this medication to build up in the body, causing side effects. If you have reduced kidney function, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Rarely, bosutinib has been reported to cause kidney failure. If you experience signs of decreasing kidney function such as decreased urine production, swelling, fatigue, or abdominal pain, contact your doctor immediately.

Liver function: Liver disease or reduced liver function may cause this medication to build up in the body, causing side effects. If you have reduced liver function or liver disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Bosutinib has been reported to cause liver failure, which can cause death.

If you experience symptoms of liver problems such as fatigue, feeling unwell, loss of appetite, nausea, yellowing of the skin or whites of the eyes, dark urine, pale stools, abdominal pain or swelling, and itchy skin, contact your doctor immediately.

Pancreatitis: Bosutinib can cause the pancreas to become inflamed. If you have a history of pancreatitis, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Report signs of pancreatitis such as abdominal pain on the upper left side, back pain, nausea, fever, chills, rapid heartbeat, or swollen abdomen to your doctor immediately.

If you have a history of pancreatitis, gallstones, alcoholism, or high triglycerides, you may be more at risk of experiencing this.

Skin reactions: Severe skin reactions have been linked to bosutinib use. Although rare, they are considered medical emergencies and require immediate medical attention.

If you experience skin blistering or peeling, a rash that covers a large area of the body, a rash that spreads quickly, or a rash combined with fever or discomfort, seek medical attention immediately.

Tumour lysis syndrome: Bosutinib, like many other cancer medications, causes many cancer cells to be suddenly killed when treatment is first started. This can overwhelm the body with waste products from the cells. As a result, the body may not be able to keep up with getting rid of all the waste. When this happens, you may have nausea, shortness of breath, cloudy urine, or joint pain. This is called tumour lysis syndrome. Your doctor may prescribe some medications to help your body get rid of the waste products. Make sure you understand how to use these medications and report any of these signs or symptoms to your doctor immediately.

Pregnancy: This medication should not be taken during pregnancy. Bosutinib may cause severe harm to a developing baby if it is taken by the mother while she is pregnant. Female partners of men taking this medication should not become pregnant. Both women and men must use a reliable method of birth control (e.g., condoms, birth control pill) during treatment and for at least 4 weeks after treatment is finished. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding: This medication may pass into breast milk. If you are a breast-feeding mother and are taking bosutinib, it may affect your baby. Due to the potential for serious harm to a baby if they are exposed to this medication, breast-feeding mothers are advised not use this medication.

Children: The safety and effectiveness of this medication have not been established for children.

There may be an interaction between bosutinib and any of the following:

• antacids (e.g., aluminum hydroxide, calcium carbonate, magnesium hydroxide)
• antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
• antiarrhythmic medications (e.g., amiodarone, disopyramide, dronedarone, flecainide, procainamide, quinidine, sotalol)
• apalutamide
• aprepitant
• "azole" antifungals (e.g., itraconazole, ketoconazole, voriconazole)
• BCG
• bosentan
• chloroquine
• ciprofloxacin
• cladribine
• cobicistat
• conivaptan
• corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
• diltiazem
• disopyramide
• diuretics (water pills; e.g., furosemide, hydrochlorothiazide, triamterene)
• domperidone
• enzalutamide
• formoterol
• grapefruit juice
• H2 antagonists (e.g., famotidine, nizatidine)
• HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., efavirenz, etravirine, nevirapine)
• HIV protease inhibitors (atazanavir, darunavir, lopinavir, ritonavir)
• laxatives
• letermovir
• lumacaftor and ivacaftor
• macrolide antibiotics (e.g., clarithromycin, erythromycin)
• mesalamine
• methadone
• mifepristone
• modafinil
• olsalazine
• other protein kinase inhibitors (e.g., crizotinib, dabrafenib, dasatinib, idelalisib, imatinib)
• pomegranate
• proton pump inhibitors (e.g., lansoprazole, omeprazole)
• quinine
• quinolone antibiotics (e.g., ciprofloxacin, norfloxacin, ofloxacin)
• rifabutin
• rifampin
• romidepsin
• St. John's wort
• salmeterol
• seizure medications (e.g., carbamazepine, clobazam, levetiracetam, phenobarbital, phenytoin, primidone, topiramate, valproic acid, zonisamide)
• sotalol
• star fruit
• sulfasalazine
• tocilizumab
• tricyclic antidepressants (e.g., clomipramine, desipramine, imipramine)
• verapamil

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.