Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium
Bosulif is indicated for the treatment of:
The recommended dose is 400 mg bosutinib once daily.
The recommended dose is 500 mg bosutinib once daily.
In clinical studies for both indications, treatment with bosutinib continued until disease progression or intolerance to therapy.
The recommended dosage of bosutinib for newly-diagnosed paediatric patients is 300 mg/m² body surface area (BSA) orally once daily and the recommended dosage for paediatric patients resistant or intolerant (R/I) to prior therapies is 400 mg/m² BSA orally once daily; dose recommendations are provided in Table 1. As appropriate, the desired dose can be attained by combining different strengths of bosutinib film-coated tablets and/or hard capsules.
Table 1. Dosing of bosutinib for paediatric patients with newly-diagnosed CP Ph+ CML or with CP Ph+ CML with resistance or intolerance to prior therapy:
| BSA | ND Recommended Dose | R/I Recommended Dose |
|---|---|---|
| 0.55 – <0.63 m² | 200 mg | 250 mg |
| 0.63 – <0.75 m² | 200 mg | 300 mg |
| 0.75 – <0.9 m² | 250 mg | 350 mg |
| 0.9 – <1.1 m² | 300 mg | 400 mg |
| ≥1.1 m² | 400 mg* | 500 mg* |
* maximum starting dose (corresponding to maximum starting dose in adult indication)
Abbreviations: AP=accelerated phase; BP=blast phase; BSA=body surface area; CML=chronic myeloid leukaemia; CP=chronic phase; ND=newly-diagnosed; Ph+=Philadelphia chromosome-positive; R/I=resistant or intolerant.
In adult patients with CML who are resistant or intolerant to prior therapy, doses can be escalated to 600 mg in those with unsatisfactory response or with signs of progression and in the absence of any Grade 3 or 4 or persistent Grade 2 adverse events.
In adult patients with newly-diagnosed CP CML, doses can be escalated by 100 mg increments to a maximum of 600 mg once daily if patients fail to demonstrate breakpoint cluster region Abelson (BCR-ABL) transcripts ≤10% at months 3 and do not have a grade 3 or 4 adverse reaction at the time of escalation and all Grade 2 non-haematological toxicities are resolved to at least Grade 1.
In paediatric patients with BSA <1.1 m² and an insufficient response after 3 months consider increasing dose by 50 mg increments up to maximum of 100 mg above BSA-adjusted recommended dose. In paediatric patients with BSA ≥1.1 m² and an insufficient response after 3 months consider increasing dose similarly to adult recommendations in 100 mg increments. If there is inadequate clinical response and further dose escalation cannot be performed in paediatric patients, treatment will be stopped.
The maximum dose in paediatric patients is 600 mg once daily in previously treated CML and 500 mg once daily in newly-diagnosed CML.
Doses greater than 600 mg/day have not been studied and, therefore, should not be given.
If clinically significant moderate or severe non-haematological toxicity develops, bosutinib should be interrupted, and may be resumed at a dose reduced by 100 mg taken once daily after the toxicity has resolved. If clinically appropriate, re-escalation to the dose prior to the dose reduction taken once daily should be considered (see section 4.4). Doses less than 300 mg/day have been used in patients; however, efficacy has not been established.
If elevations in liver transaminases >5 × institutional upper limit of normal (ULN) occur, bosutinib should be interrupted until recovery to ≤2.5 × ULN and may be resumed at 400 mg once daily thereafter. If recovery takes longer than 4 weeks, discontinuation of bosutinib should be considered. If transaminase elevations ≥3 × ULN occur concurrently with bilirubin elevations >2 × ULN and alkaline phosphatase <2 × ULN, bosutinib should be discontinued (see section 4.4).
For NCI Common Terminology Criteria for Adverse Events (CTCAE) Grade 3-4 diarrhoea, bosutinib should be interrupted and may be resumed at 400 mg once daily upon recovery to grade ≤1 (see section 4.4).
In paediatric patients, dose adjustments for non-haematologic toxicities can be conducted similarly to adults, however the dose reduction increments may differ. For paediatric patients with BSA <1.1 m², consider dose reduction by 50 mg initially followed by additional 50 mg reductions if the adverse drug reaction (ADR) persists, in line with recommendations from Table 2. For paediatric patients with BSA ≥1.1 m² reduce dose similarly to adults.
Dose reductions are recommended for severe or persistent neutropenia and thrombocytopenia as described in Table 2:
Table 2. Dose adjustments for neutropenia and thrombocytopenia in adult and paediatric patients:
| ANCa <1.0 × 109/L and/or Platelets <50 × 109/L | Hold bosutinib until ANC ≥1.0 × 109/L and platelets ≥50 × 109/L. Resume treatment with bosutinib at the same dose if recovery occurs within 2 weeks. If blood counts remain low for >2 weeks, upon recovery reduce dose by 100 mg in adult patients and paediatric patients with BSA ≥1.1 m² or by 50 mg in paediatric patients with BSA <1.1 m² and resume treatment. If cytopoenia recurs, reduce dose by an additional 100 mg in adult patients and paediatric patients with BSA ≥1.1 m² upon recovery, or by an additional 50 mg in paediatric patients with BSA <1.1 m² and resume treatment. Doses less than 300 mg/day have been used in adult patients and paediatric patients with BSA ≥1.1 m²; however, efficacy has not been established. Doses less than 300 mg/m² have been used in paediatric patients however efficacy has not been established. |
a ANC=absolute neutrophil count; BSA=body surface area
If a dose is missed by more than 12 hours, the patient should not be given an additional dose. The patient should take the usual prescribed dose on the following day.
No specific dose recommendation is necessary in the elderly. Since there is limited information in the elderly, caution should be exercised in these patients.
Patients with serum creatinine >1.5×ULN were excluded from CML studies. Increasing exposure (area under curve [AUC]) in patients with moderate and severe renal impairment during studies was observed.
In adult patients with moderate renal impairment (creatinine clearance [CLCr] 30 to 50 mL/min, estimated by the Cockcroft-Gault formula), the recommended dose of bosutinib is 300 mg daily with food (see sections 4.4 and 5.2).
In adult patients with severe renal impairment (CLCr <30 mL/min, estimated by the Cockcroft-Gault formula), the recommended dose of bosutinib is 200 mg daily with food (see sections 4.4 and 5.2).
Dose escalation to 400 mg once daily with food for adult patients with moderate renal impairment or to 300 mg once daily for patients with severe renal impairment may be considered if they do not experience severe or persistent moderate adverse reactions and if they do not achieve an adequate haematological, cytogenetic, or molecular response.
In adult patients with moderate renal impairment (CLCr 30 to 50 mL/min, calculated by the Cockcroft-Gault formula), the recommended dose of bosutinib is 400 mg daily (see sections 4.4 and 5.2).
In patients with severe renal impairment (CLCr <30 mL/min, calculated by the Cockcroft-Gault formula), the recommended dose of bosutinib is 300 mg daily (see sections 4.4 and 5.2).
Dose escalation to 500 mg once daily for adult patients with moderate renal impairment or to 400 mg once daily in patients with severe renal impairment may be considered in those who did not experience severe or persistent moderate adverse reactions, and if they do not achieve an adequate haematological, cytogenetic, or molecular response.
In clinical studies, patients with uncontrolled or significant cardiac disease (e.g., recent myocardial infarction, congestive heart failure or unstable angina) were excluded. Caution should be exercised in patients with relevant cardiac disorders (see section 4.4).
In clinical studies, patients with recent or ongoing clinically significant gastrointestinal disorder (e.g., severe vomiting and/or diarrhoea) were excluded. Caution should be exercised in patients with recent or ongoing clinically significant gastrointestinal disorder (see section 4.4).
The safety and efficacy of bosutinib in paediatric patients below the age of 1 year with newly-diagnosed, or resistant or intolerant Ph+ CML in CP have not been established. No data are available. The information from paediatric patients below the age of 6 years are too limited so that no dose recommendations can be made (see section 5.1).
Bosulif should be taken orally once daily with food (see section 5.2).
The film-coated tablets should be swallowed whole. Do not cut, crush, break or chew the film-coated tablets.
The hard capsules may be swallowed whole. For patients who are unable to swallow a whole hard capsule(s), each hard capsule can be opened and the contents mixed with applesauce or yogurt. Mixing the hard capsule contents with applesauce or yogurt is no substitute of a proper meal, the dose should be taken with food to increase gastrointestinal tolerability.
If mixing with applesauce or yogurt, patients should immediately consume the full mixture in its entirety, without chewing. The mixture should not be stored for later use. If the entire preparation is not swallowed, an additional dose should not be administered, and it is advised to wait until the next day to resume dosing. In order to facilitate the administration, the recommended volume of applesauce or yogurt is provided in Table 3.
Table 3. Bosutinib dose using hard capsules and soft food volumes:
| Dose | Volume of Applesauce or Yogurt |
|---|---|
| 200 mg | 20 mL (4 teaspoons) |
| 250 mg | 25 mL (5 teaspoons) |
| 300 mg | 30 mL (6 teaspoons) |
| 350 mg | 30 mL (6 teaspoons) |
| 400 mg | 35 mL (7 teaspoons) |
| 500 mg | 45 mL (9 teaspoons) |
Experience with bosutinib overdose in clinical studies was limited to isolated cases. Patients who take an overdose of bosutinib should be observed and given appropriate supportive treatment.
Film-coated tablets: 4 years.
Hard capsules: 3 years.
Film-coated tablets: This medicinal product does not require any special storage conditions.
Hard capsules: Do not store above 30 °C. Store in the original package in order to protect from light.
White opaque 3-ply PVC/Polychlorotrifluoroethene/PVC blister sealed with push-through foil backing containing either 14 or 15 tablets.
Bosulif 100 mg film-coated tablets: Each carton contains 28, 30 or 112 tablets.
Bosulif 400 mg film-coated tablets: Each carton contains 28 or 30 tablets.
Bosulif 500 mg film-coated tablets: Each carton contains 28 or 30 tablets.
High-density polyethylene (HDPE) bottle and polypropylene (PP) closure with heat induction seal (HIS).
Bosulif 50 mg hard capsules: Cartons of one bottle containing 30 hard capsules.
Bosulif 100 mg hard capsules: Cartons of one bottle containing 150 hard capsules.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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