iazem, atazanavir, aprepitant, amprenavir, fosamprevir, crizotinib, imatinib, verapamil, grapefruit products and ciprofloxacin) [see Drug Interactions (7.1)].
Concomitant Use With CYP3A Inducers
Avoid the concomitant use of strong or moderate CYP3A inducers with Bosulif as a large reduction in exposure is expected (strong CYP3A inducers include rifampin, phenytoin, carbamazepine, St. John's Wort, rifabutin and phenobarbital. Moderate CYP3A inducers include bosentan, nafcillin, efavirenz, modafinil and etravirine) [see Drug Interactions (7.2)].
Hepatic Impairment
In patients with pre-existing mild, moderate, and severe hepatic impairment, the recommended dose of Bosulif is 200 mg daily. A daily dose of 200 mg in patients with hepatic impairment is predicted to result in an area under the concentration curve (AUC) similar to the AUC seen in patients with normal hepatic function receiving 500 mg daily. However, there are no clinical data for efficacy at the dose of 200 mg once daily in patients with hepatic impairment and CML [see Use in Special Populations (8.6)].
Dosage Forms and Strengths
100 mg tablets: yellow, oval, biconvex, film-coated tablets debossed with "Pfizer" on one side and "100" on the other.
500 mg tablets: red, oval, biconvex, film-coated tablets debossed with "Pfizer" on one side and "500" on the other.
Contraindications
Hypersensitivity to Bosulif. In the Bosulif clinical trials, anaphylactic shock occurred in less than 0.2% of treated patients.
Warnings and Precautions
Gastrointestinal Toxicity
Diarrhea, nausea, vomiting, and abdominal pain occur with Bosulif treatment. Monitor and manage patients using standards of care, including antidiarrheals, antiemetics, and/or fluid replacement. In the single-arm Phase 1/2 clinical trial, the median time to onset for diarrhea (all grades) was 2 days and the median duration per event was 1 day. Among the patients who experienced diarrhea, the median number of episodes of diarrhea per patient during treatment with Bosulif was 3 (range 1–221). To manage gastrointestinal toxicity, withhold, dose reduce, or discontinue Bosulif as necessary [see Dosage and Administration (2.3) and Adverse Reactions (6)].
Myelosuppression
Thrombocytopenia, anemia and neutropenia occur with Bosulif treatment. Patients with CML who are receiving Bosulif should have a complete blood count performed weekly for the first month and then monthly thereafter, or as clinically indicated. To manage myelosuppression, withhold, dose reduce, or discontinue Bosulif as necessary [see Dosage and Administration (2.4) and Adverse Reactions (6)].
Hepatic Toxicity
One case consistent with drug induced liver injury (defined as concurrent elevations in ALT or AST greater than or equal to 3 × ULN with total bilirubin greater than 2 × ULN and alkaline phosphatase less than 2 × ULN) occurred in a trial of Bosulif in combination with letrozole. The patient recovered fully following discontinuation of Bosulif. This case represented 1 out of 1209 patients in Bosulif clinical trials.
In the 546 patients from the safety population, the incidence of ALT elevation was 17% and AST elevation was 14 %. Twenty per cent of the patients experienced an increase in either ALT or AST. Most cases of transaminase elevations occurred early in treatment; of patients who experienced transaminase elevations of any grade, more than 80% experienced their |
