Bosutinib (BOSULIF)

Philadelphia chromosome positive (Ph+) Chronic myeloid leukemia

Philadelphia chromosome positive (Ph+) Chronic myeloid leukemia

• Oral: Chronic phase, newly diagnosed - 400 mg once daily continuously until disease progression or unacceptable toxicity  
• Oral: Chronic, accelerated, or blast phase, failure of prior lines of therapy - 500 mg once daily continuously until disease progression or unacceptable toxicity
• Note: dose may be increased to 600mg in patients with less than or equal to grade 2 adverse effects, who did not reach complete hematological response by 8 weeks, or who did not reach a complete cytogenetic response by 12 weeks

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Available as 100mg, 400mg and 500 mg film-coated tablets. Tablets should NOT be crushed or broken. Store at room temperature.

BCR-ABL Tyrosine Kinase Inhibitor

Take with food

If a dose is missed, patients should be instructed to take it as soon as they can if it is within 12 hours of the missed dose. If it is over 12 hours since the missed dose, patients should skip the missed dose and resume with the next scheduled dose.

Common: Neutropenia, Thrombocytopenia, Abdominal pain, Diarrhea, Nausea, Vomiting, Infections, ALT increase, AST increase, Lipase increase.

Less Common: Hypersensitivity, QT prolongation, Fractures, Pericardial effusion, Pleural effusion, and Pulmonary/peripheral edema.

The adverse effects listed above are not exhaustive. Please refer to the relevant product monograph for full details.

Baseline before treatment: CBC & differential, platelets, ALT, bilirubin, serum creatinine, BUN, sodium, potassium, magnesium, calcium, phosphorous, serum lipase, body weight, bone marrow examination for cytogenetic analysis, FISH, RT-PCR (for BCR/ABL transcripts), BCR-ABL mutational analysis, ECG, HBsAg, HBcoreAb

Weeks 1-4 during treatment: CBC & differential, Platelets. ECG should be repeated 1 week after initially starting Bosutinib, and 1 week after any dose change

Weeks 4-12 during treatment: CBC & differential, Platelets, ALT, Bilirubin, serum creatinine, uric acid, sodium, potassium, magnesium, calcium, phosphorous, serum lipase

After 3 months during treatment:

• CBC & differential, Platelets, Serum Creatinine, Uric Acid monthly. 
• ALT, Bilirubin every 3 months or as clinically indicated.
• Sodium, potassium, magnesium, calcium, phosphorous, serum lipase every 3 months or as clinically indicated.
• Bone density scan as clinical indicated for at-risk patients (endocrine abnormalities, history of osteoporosis).
• BCR-ABL transcripts every 3 months until MMR achieved and maintained for at least 12 months. 
  • Frequency of transcript testing can then move to every 6 months.

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• Proton pump inhibitors may decrease bosutinib drug levels. Short-acting antacids should be considered as an alternative. Administration of Bosutinib and antacids should be separated (e.g take Bosutinib in the morning, and antacids in the evening).
• May increase the risk for QT interval prolongation. Avoid concurrent therapy with drugs associated with QTc prolongation and/or Torsades de pointes, if possible. If unavoidable, monitor for QT prolongation or cardiac arrhythmias.
• This drug can impact or be impacted by metabolic enzymes for absorption and excretion. Many drugs can also affect or be affected by these enzymes, so please consult with pharmacy to assess for interactions.
• Avoid grapefruit, grapefruit juice, Seville oranges, or Seville orange juice
• Current drug interaction databases should be consulted for more information.

• Avoid in pregnancy and lactation.
• Treatment is associated with fluid retention (pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema). Patients should be weighed regularly and monitored for signs and symptoms of fluid retention.
• Treatment with Bosutinib is associated with events of diarrhea and vomiting.  Patients with these events should be managed using standard of care treatment, including antidiarrheal medication, antiemetics and/or fluid replacement.
• Reactivation of hepatitis B virus (HBV) has been reported in patients who are chronic carriers of HBV and received BCR-ABL TKIs. Patients should be tested for HBV infection prior to initiating treatment. Carriers of HBV must be monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy.

BC Cancer. BC Cancer Drug Manual. Bosutinib.  Vancouver, British Columbia: BC Cancer Agency. Available at:  http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Bosutinib_monograph.pdf. Updated January  1, 2024. Accessed January 22, 2024.

Lexicomp. Bosutinib Monograph. In: Lexi-Drugs. Hudson, Ohio: Lexi-Comp, Inc. Available at: https://online-lexi-com.qe2a-proxy.mun.ca/lco/action/doc/retrieve/docid/patch_f/3888002?cesid=3SfeLoq1kjK&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dbosutinib%26t%3Dname%26acs%3Dfalse%26acq%3Dbosutinib. Updated January 24, 2024. Accessed January 31, 2024.

Cancer Care Ontario. Bosutinib Monograph. Drug Formulary. Toronto, Ontario: Cancer Care Ontario. Available at: https://www.cancercareontario.ca/en/drugformulary/drugs/monograph/44371. Updated March 2021. Accessed January 22, 2024Pfizer Canada Inc. BOSULIF® Product Monograph. Kirkland, Quebec. Updated July 29, 2015.