Generic name: BOSUTINIB MONOHYDRATE 100mg
Dosage form: tablet, film coated
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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.
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.
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.
Dose Adjustments for Myelosuppression
Dose reductions for severe or persistent neutropenia and thrombocytopenia are described below (Table 1).
|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.|
|Platelets less than 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 not been evaluated.
Concomitant Use With CYP3A Inhibitors
Avoid the concomitant use of strong or moderate CYP3A and/or P-gp inhibitors with BOSULIF as an increase in bosutinib plasma concentration is expected (strong CYP3A inhibitors include ritonavir, indinavir, nelfinavir, saquinavir, ketoconazole, boceprevir, telaprevir, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone and conivaptan. Moderate CYP3A inhibitors include fluconazole, darunavir, erythromycin, diltiazem, 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)].
Recommended Starting Dosage with Hepatic Impairment or Renal Impairment
|Organ Function Status||Recommended Starting Dosage|
|Normal hepatic and renal function||500 mg once daily|
| Mild (Child-Pugh A), Moderate (Child-Pugh B) or severe (Child-Pugh C)||200 mg daily|
| Creatinine clearance 30 to 50 mL/min||400 mg daily|
| Creatinine clearance less than 30 mL/min||300 mg daily|
|[see Use in Specific Populations (8.6,8.7) and Clinical Pharmacology (12.3)].|