AP=accelerated phase; BP=blast phase; CP=chronic phase.

Indication

BOSULIF® (bosutinib) is indicated for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy.

Important Safety Information

Contraindication: Hypersensitivity to BOSULIF. Anaphylactic shock occurred in less than 0.2% of treated patients.

Gastrointestinal Toxicity: Diarrhea, nausea, vomiting, and abdominal pain can occur. In the clinical trial, median time to onset for diarrhea was 2 days, median duration was 1 day, and median number of episodes per patient was 3 (range 1-221). Monitor and manage patients using standards of care, including antidiarrheals, antiemetics, and/or fluid replacement. Withhold, dose reduce, or discontinue BOSULIF as necessary.

Myelosuppression: Thrombocytopenia, anemia, and neutropenia can occur. Perform complete blood counts weekly for the first month and then monthly or as clinically indicated. Withhold, dose reduce, or discontinue BOSULIF as necessary.

Hepatic Toxicity: Twenty percent of patients experienced an increase in either ALT or AST. Liver enzyme elevation usually occurs early in treatment. Perform hepatic enzyme tests monthly for the first 3 months and as clinically indicated. In patients with transaminase elevations, monitor liver enzymes more frequently. Drug-induced liver injury has occurred. Withhold, dose reduce, or discontinue BOSULIF as necessary. In patients with mild, moderate, and severe hepatic impairment, the recommended starting dose is 200 mg daily.

Renal Toxicity: An on-treatment decline in estimated glomerular filtration rate has occurred in patients treated with BOSULIF. Monitor renal function at baseline and during therapy, with particular attention to patients with preexisting renal impairment or risk factors. Consider dose adjustment in patients with baseline and treatment emergent renal impairment. The recommended starting doses for patients with severe renal impairment (CrCL<30 mL/min) or moderate renal impairment (CrCL 30-50 mL/min) are 300 mg and 400 mg daily, respectively.

Fluid Retention: Fluid retention can occur and may cause pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Monitor and manage patients using standards of care. Interrupt, dose reduce, or discontinue BOSULIF as necessary.

Embryofetal Toxicity: BOSULIF may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised of potential hazard to the fetus and to avoid becoming pregnant while receiving BOSULIF.

Adverse Reactions: The most common adverse reactions observed in greater than 20% of patients in the Phase 1/2 safety population (N=546) were diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue.
The most common Grade 3/4 adverse reactions and laboratory abnormalities observed in greater than 10% of patients were thrombocytopenia, anemia, and neutropenia.

CYP3A Inhibitors and Inducers: Avoid concurrent use with strong or moderate CYP3A inhibitors or inducers.

Proton Pump Inhibitors: Consider using short-acting antacids or H2 blockers instead of PPIs. Separate antacid or H2 blocker dosing and BOSULIF dosing by more than 2 hours.

Substrates of P-glycoprotein: BOSULIF may increase the plasma concentrations of drugs that are P-gp substrates, such as digoxin.

Nursing Mothers: Given the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or BOSULIF.

Please see full Prescribing Information.

aReferenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myelogenous Leukemia V1.2015. © 2015 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN content are trademarks owned by the National Comprehensive Cancer Network, Inc.