Bosutinib

BOSULIF is indicated for the treatment of: • Adult and pediatric patients 1 year of age and older with chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML), newly-diagnosed or resistant or intolerant to prior therapy. • Adult patients with accelerated phase (AP), or blast phase (BP) Ph+ CML with resistance or intolerance to prior therapy. BOSULIF is a kinase inhibitor indicated for the treatment of • adult and pediatric patients 1 year of age and older with chronic phase Ph+ chronic myelogenous leukemia (CML), newly-diagnosed or resistant or intolerant to prior therapy. • adult patients with accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.

Bosutinib is a TKI. Bosutinib inhibits the BCR-ABL kinase that promotes CML, it is also an inhibitor of Src-family kinases including Src, Lyn, and Hck. Bosutinib inhibited 16 of 18 imatinib-resistant forms of BCR-ABL kinase expressed in murine myeloid cell lines. Bosutinib did not inhibit the T315I and V299L mutant cells.

• Adult patients with newly-diagnosed chronic phase Ph+ CML: 400 mg orally once daily with food. • Adult patients with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy: 500 mg orally once daily with food. • Pediatric patients with newly-diagnosed chronic phase Ph+ CML: 300 mg/m 2 orally once daily with food. • Pediatric patients with chronic phase Ph+ CML with resistance or intolerance to prior therapy: 400 mg/m 2 orally once daily with food. • Consider dose escalation by increments of 100 mg once daily to a maximum of 600 mg daily in adult patients who do not reach complete hematologic, cytogenetic, or molecular response and do not have Grade 3 or greater adverse reactions.

BOSULIF is contraindicated in patients with a history of hypersensitivity to BOSULIF. Reactions have included anaphylaxis. Hypersensitivity to BOSULIF.

• Gastrointestinal Toxicity: Monitor and manage as necessary. Withhold, dose reduce, or discontinue BOSULIF. • Myelosuppression: Monitor blood counts and manage as necessary. Withhold, dose reduce, or discontinue BOSULIF. • Hepatic Toxicity: Monitor liver enzymes at least monthly for the first 3 months and as needed. Withhold, dose reduce, or discontinue BOSULIF. • Cardiovascular Toxicity: Monitor and manage as necessary. Interrupt, dose reduce, or discontinue BOSULIF. • Fluid Retention: Monitor patients and manage using standard of care treatment. Interrupt, dose reduce, or discontinue BOSULIF. • Renal Toxicity: Monitor patients for renal function at baseline and during therapy with BOSULIF. • Embryo-Fetal Toxicity: BOSULIF can cause fetal harm. Advise female patients of reproductive potential of potential risk to a fetus and to use effective contraception.

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: • Gastrointestinal toxicity. • Myelosuppression. • Hepatic toxicity. • Cardiovascular toxicity. • Fluid retention. • Renal toxicity. • Most common adverse reactions (≥20%), in adult and pediatric patients with CML are diarrhea, abdominal pain, vomiting, nausea, rash, fatigue, hepatic dysfunction, headache, pyrexia, decreased appetite respiratory tract infection, and constipation.

• Strong and Moderate CYP3A Inhibitors: Avoid concomitant use with BOSULIF. • Strong CYP3A Inducers: Avoid concomitant use with BOSULIF. • Proton Pump Inhibitors: Use short-acting antacids or H2 blockers as an alternative to proton pump inhibitors.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). Storage Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) and Store and Dispense in Original Container.