Bosutinib

Anemia, neutropenia, and thrombocytopenia may occur. May require treatment interruption, dose reduction, or discontinuation. Monitor blood counts weekly during first month, then monthly thereafter (or as clinically indicated).

Fluid retention, manifesting as pericardial effusion, pleural effusion, pulmonary edema and/or peripheral edema may occur; may be severe. Monitor for fluid retention (eg, weight gain) and manage appropriately; may require treatment interruption, dose reduction, or discontinuation.

Diarrhea, nausea, vomiting, and abdominal pain may occur. Monitor; may require treatment interruption, dose reduction, discontinuation, or other management (eg, medications or fluids). For patients experiencing diarrhea (all grades), the median time to onset in patients with CML resistant or intolerant to prior therapy was 2 days; median duration (per event) was 2 days and the median number of diarrhea episodes per patient was 3 (range: 1 to 268); manage diarrhea with antidiarrheals and/or fluid replacement. Similarly, the median time to onset for diarrhea (all grades) in patients with newly-diagnosed CML was 3 days; the median duration per events was 3 days. Bosutinib is associated with a moderate emetic potential (Hesketh 2017; Roila 2016); nausea and vomiting may be managed with antiemetics and fluid replacement. GI hemorrhages have also been reported.

Serum transaminase (ALT and/or AST) elevations have been reported. In patients with transaminase elevation, ~80% developed the transaminase elevation within the first 3 months of therapy. In a clinical study in patients with newly-diagnosed chronic phase CML, the median time to onset of elevated ALT and AST was 32 and 43 days, respectively; the median duration was 20 and 15 days, respectively. In patients with CML resistant or intolerant to prior therapy, the mediation time to onset of ALT and AST elevation was 35 and 33 days, respectively, and the median duration (for each) was 21 days. One case of drug-induced liver injury has been reported in a breast cancer clinical trial (not an approved indication); full recovery occurred after discontinuation. Monitor transaminases monthly for the first 3 months (and as clinically indicated; monitor more frequently if elevations occur). May require therapy interruption, dosage reduction, or therapy discontinuation.

Hypersensitivity reactions have been reported, including anaphylaxis and anaphylactic shock (rare).

Acute pancreatitis has been reported (rare); use caution in patients with a prior history of pancreatitis.

QTcF >500 milliseconds was observed rarely in clinical trials (Cortes 2012); patients with significant or uncontrolled cardiovascular disease (including prolonged QT interval at baseline) were not studied.

Declines in glomerular filtration rates throughout bosutinib treatment have been observed in clinical studies; monitor renal function at baseline and during therapy, particularly in patients with preexisting impairment or other risk factors for renal dysfunction. Consider dosage adjustment in patients with renal dysfunction at baseline or with treatment emergent impairment. Disease-related concerns:

Bosutinib exposure is increased in patients with hepatic impairment; dose reduction is recommended.

Bosutinib exposure is increased in patients with moderate or severe renal impairment. Consider dosage adjustment in patients with renal dysfunction at baseline or with treatment emergent impairment. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Proton pump inhibitors (PPIs) may decrease bosutinib effects; consider using short acting antacids or H2 antagonists instead of PPIs. Separate administration of antacids or H2 antagonists from bosutinib by at least 2 hours.