ML
6.2 Additional Data from Multiple Clinical Trials
7 DRUG INTERACTIONS
7.1 Drugs That May Increase Bosutinib Plasma Concentrations
7.2 Drugs That May Decrease Bosutinib Plasma Concentrations
7.3 Drugs That May Have Their Plasma Concentrations Altered By Bosutinib
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Hepatic Impairment
8.7 Renal Impairment
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.3 Pharmacokinetics
12.4 QT/QTc Prolongation
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Storage
16.3 Handling and Disposal
17 PATIENT COUNSELING INFORMATION
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
BOSULIF 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.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosing
The recommended dose and schedule of BOSULIF is 500 mg orally once daily with food. Continue treatment with BOSULIF until disease progression or patient intolerance.
If a dose is missed beyond 12 hours, the patient should skip the dose and take the usual prescribed dose on the following day.
2.2 Dose Escalation
Consider dose escalation to 600 mg once daily with food in patients who do not reach complete hematological response (CHR) by week 8 or a complete cytogenetic response (CCyR) by week 12, who did not have Grade 3 or higher adverse reactions, and who are currently taking 500 mg daily.
2.3 Dose Adjustments for Non-Hematologic Adverse Reactions
Elevated liver transaminases: If elevations in liver transaminases greater than 5 × institutional upper limit of normal (ULN) occur, withhold BOSULIF until recovery to less than or equal to 2.5 × ULN and resume at 400 mg once daily thereafter. If recovery takes longer than 4 weeks, discontinue BOSULIF. If transaminase elevations greater than or equal to 3 × ULN occur concurrently with bilirubin elevations greater than 2 × ULN and alkaline phosphatase less than 2 × ULN (Hy's law case definition), discontinue BOSULIF [see Warnings and Precautions (5.3)].
Diarrhea: For NCI CTCAE Grade 3–4 diarrhea (increase of greater than or equal to 7 stools/day over baseline/pretreatment), withhold BOSULIF until recovery to Grade less than or equal to 1. BOSULIF may be resumed at 400 mg once daily [see Warnings and Precautions (5.1)].
For other clinically significant, moderate or severe non-hematological toxicity, withhold BOSULIF until the toxicity has resolved, then consider resuming BOSULIF at 400 mg once daily. If clinically appropriate, consider re-escalating the dose of BOSULIF to 500 mg once daily.
2.4 Dose Adjustments for Myelosuppression
Dose reductions for severe or persistent neutropenia and thrombocytopenia are described below (Table 1).
Table 1: Dose Adjustments for Neutropenia and Thrombocytopenia
*
Absolute Neutrophil Count
ANC* less than 1000×106/L Withhold BOSULIF until ANC greater than or equal to1000×106/L and platelets greater than or equal to 50,000×106/L.
or
Platelets less than 50,0 |
