BOSULIF safety information
Important Safety Information
Contraindication: History of hypersensitivity to BOSULIF. Reactions have included anaphylaxis. Anaphylactic shock occurred in less than 0.2% of treated patients in clinical trials.
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 2 days, and median number of episodes per patient was 3 (range 1-268). 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. The median time to onset of increased ALT and AST was 35 and 33 days, respectively, and the median duration for each was 21 days. Perform hepatic enzyme tests at least monthly for the first 3 months and as clinically indicated. In patients with transaminase elevations, monitor liver enzymes more frequently. One case consistent with drug-induced liver injury occurred in a trial of BOSULIF in combination with letrozole. Withhold, dose reduce, or discontinue BOSULIF as necessary. In patients with mild, moderate, or 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 for renal dysfunction. 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. In the clinical trial, Grade 3/4 fluid retention was reported in 26 patients (5%). Monitor and manage patients using standards of care. Interrupt, dose reduce, or discontinue BOSULIF as necessary.
Embryofetal Toxicity: BOSULIF can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised of potential hazard to the fetus. Advise females of reproductive potential to use effective contraceptive measures to prevent pregnancy while being treated with BOSULIF and for at least 30 days after the final dose.
Adverse Reactions: The most common adverse reactions observed in greater than or equal to 20% of patients in the Phase 1/2 safety population (N=546) were diarrhea, nausea, thrombocytopenia, rash, vomiting, abdominal pain, respiratory tract infection, anemia, pyrexia, liver test abnormalities, fatigue, cough, and headache. The most common Grade 3/4 adverse reactions and laboratory abnormalities observed in greater than 10% of patients were thrombocytopenia, neutropenia, and anemia.
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 to avoid a reduction in BOSULIF exposure. Separate antacid or H2 blocker dosing and BOSULIF dosing by more than 2 hours.
Nursing Mothers: Given the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or BOSULIF, taking into account the importance of the drug to the mother.
BOSULIF® (bosutinib) is indicated for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia
Please see full Prescribing Information.