first event within the first 3 months. The median time to onset of increased ALT and AST was 30 and 33 days, respectively, and the median duration for each was 21 days.
Perform monthly hepatic enzyme tests for the first three months of treatment with Bosulif and as clinically indicated. In patients with transaminase elevations, monitor liver enzymes more frequently. Withhold, dose reduce, or discontinue Bosulif as necessary [see Dosage and Administration (2.3) and Adverse Reactions (6)].
Fluid Retention
Fluid retention occurs with Bosulif and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema.
In the single-arm Phase 1/2 clinical trial in 546 patients with CML treated with prior therapy, severe fluid retention was reported in 14 patients (3%). Specifically, 9 patients had a Grade 3 or 4 pleural effusion, 3 patients experienced both Grade 3 or Grade 4 pleural and pericardial effusions, 1 patient experienced Grade 3 peripheral and pulmonary edema, and 1 patient had a Grade 3 edema.
Monitor and manage patients using standards of care. Interrupt, dose reduce or discontinue Bosulif as necessary [see Dosage and Administration (2.3) and Adverse Reactions (6)].
Embryofetal Toxicity
There are no adequate and well controlled studies of Bosulif in pregnant women. Bosulif can cause fetal harm when administered to a pregnant woman. Bosutinib caused embryofetal toxicities in rabbits at maternal exposures that were greater than the clinical exposure at the recommended bosutinib dose of 500 mg/day. Females of reproductive potential should be advised to avoid pregnancy while being treated with Bosulif. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].
Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections of the labeling:
•Gastrointestinal toxicity [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)].
•Myelosuppression [see Dosage and Administration (2.4) and Warnings and Precautions (5.2)].
•Hepatic toxicity [see Dosage and Administration (2.5) and Warnings and Precautions (5.3)].
•Fluid retention [see Warnings and Precautions (5.4)].
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Serious adverse reactions reported include anaphylactic shock [see Contraindications (4)], myelosuppression, gastrointestinal toxicity (diarrhea), fluid retention, hepatoxicity and rash.
Adverse reactions of any toxicity grade reported for greater than 20% of patients in the Phase 1/2 safety population (n=546) were diarrhea (82%), nausea (46%), thrombocytopenia (41%), vomiting (39%), abdominal pain (37%), rash (35%), anemia (27%), pyrexia (26%), and fatigue (24%).
Imatinib-Resistant or -Intolerant Ph+ Chronic Phase (CP), Accelerated Phase (AP), and Blast Phase (BP) CML
The single-arm Phase 1/2 clinical trial enrolled patients with Ph+ chronic, accelerated, or blast phase chronic myelogenous leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) with resistance or intolerance to prior therapy. The safety population (received at least 1 dose of Bosu |
