2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosing
The recommended dose is taken orally once daily with food. The tablet is to be swallowed whole and should not be broken or cut. Continue treatment with BOSULIF until disease progression or intolerance to therapy.
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
In clinical studies of adult Ph+ CML patients, dose escalation by increments of 100 mg once daily to a maximum of 600 mg once daily was allowed in patients who did not achieve or maintain a hematologic, cytogenetic, or molecular response and who did not have Grade 3 or higher adverse reactions at the recommended starting dosage.
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 National Cancer Institute Common Terminology Criteria for Adverse Events (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 a dose reduced by 100 mg taken once daily. If clinically appropriate, consider re-escalating the dose of BOSULIF to the starting dose taken once daily. Doses less than 300 mg/day have been used in patients; however, efficacy has not been established.
2.4 Dose Adjustments for Myelosuppression
Dose reductions for severe or persistent neutropenia and thrombocytopenia are described below (Table 1).
| |
ANC* less than 1000×106/L or Platelets less than 50,000×106/L | Withhold BOSULIF until ANC greater than or equal to1000×106/L and platelets greater than or equal to 50,000×106/L. Resume treatment with BOSULIF at the same dose if recovery occurs within 2 weeks. If blood counts remain low for greater than 2 weeks, upon recovery, reduce dose by 100 mg and resume treatment. If cytopenia recurs, reduce dose by an additional 100 mg upon recovery and resume treatment. Doses less than 300 mg/day have been used in patients; however, efficacy has not been established. |
2.5 Dose Adjustments for Renal Impairment or Hepatic Impairment
The recommended starting doses for patients with renal and hepatic impairment are described in Table 2 below.
| Recommended Starting Dosage | |||
|---|---|---|---|
| [see Use in Specific Populations (8.6, 8.7) and Clinical Pharmacology (12.3)]. | |||
| Abbreviations: CML=chronic myelogenous leukemia; Ph+=Philadelphia chromosome-positive. | |||
| |||
| Newly-diagnosed chronic phase Ph+ CML2 | Chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy | |
Normal renal and hepatic function | 400 mg daily | 500 mg daily | |
Renal impairment | |||
| Creatinine clearance 30 to 50 mL/min | 300 mg daily | 400 mg daily |
| Creatinine clearance less than 30 mL/min | 200 mg daily | 300 mg daily |
Hepatic impairment | |||
| Mild (Child-Pugh A), Moderate (Child-Pugh B) or Severe (Child-Pugh C) | 200 mg daily* | 200 mg daily* |