Bosutinib
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Handling and access
NIOSH hazardous drug
Table 2NIOSH lists bosutinib as a hazardous drug. AHFS class: 10:00 antineoplastic agents.
- Meets the NIOSH definition of a hazardous drug (carcinogenicity, developmental or reproductive toxicity, organ toxicity at low doses, or genotoxicity) without MSHI or a Group 1 or 2A carcinogen classification.
- Only a developmental and/or reproductive hazard: precautions matter most for workers who are pregnant, breastfeeding, or trying to conceive.
Handle with the precautions your facility uses for hazardous drugs (USP <800>). NIOSH's Managing Hazardous Drug Exposures lists controls by drug form and activity.
Dosing in kidney impairment
Dosage Adjustments for Renal Impairment or Hepatic Impairment The recommended starting doses for patients with renal and hepatic impairment are described in Table 4 below. [See table below.] 300 mg daily Hepatic impairment Mild (Child-Pugh A), Moderate (Child-Pugh B) or Severe (Child-Pugh C) 200 mg daily 200 mg daily [See table below.] 150 mg 100 mg 100 mg Pediatric 0.63 to < 0.75 m 2 200 mg 150 mg 100 mg 100 mg Pediatric 0.75 to < 0.9 m 2 250 mg 200 mg 150 mg 100 mg Pediatric 0.9 to < 1.1 m 2 300 mg 200 mg 200 mg 150 mg Pediatric ≥ 1.1 m 2 400 mg 300 mg 200 mg 200 mg CP Ph+ CML with Resistance or Intolerance to Prior Therapy Recommended Starting Dose (Once Daily) By Organ Function Pediatric Patients by Separated BSA Band Normal renal and hepatic function Renal Impairment: Creatinine clearance 30 to 50 mL/min Renal Impairment: Creatinine clearance less than 30 mL/min Hepatic Impairment: Mild (Child-Pugh A), Moderate (Child-Pugh B) or Severe (Child-Pugh C) Pediatric < 0.55 m 2 200 mg 150 mg 100 mg 100 mg Pediatric 0.55 to < 0.63 m 2 250 mg 200 mg 150 mg 100 mg Pediatric 0.63 to < 0.75 m 2 300 mg 200 mg 200 mg 150 mg Pediatric 0.75 to < 0.9 m 2 350 mg 250 mg 200 mg 150 mg Pediatric 0.9 to < 1.1 m 2 400 mg 300 mg 250 mg 200 mg Pediatric ≥ 1.1 m 2 500 mg 400 mg 300 mg 200 mg
| Recommended Starting Dosage | |||
|---|---|---|---|
| [see Use in Specific Populations (8.6, 8.7) and Clinical Pharmacology (12.3)]. | |||
| Newly-diagnosed chronic phase Ph+ CML | 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 | |
| [see Use in Specific Populations (8.6, 8.7) and Clinical Pharmacology (12.3)]. | ||||
| Newly-Diagnosed CP Ph+ CML Recommended Starting Dose (Once Daily) By Organ Function | ||||
| Pediatric Patients by Separated BSABSA=Body Surface Area Band | Normal renal and hepatic function | Renal Impairment: Creatinine clearance 30 to 50 mL/min | Renal Impairment: Creatinine clearance less than 30 mL/min | Hepatic Impairment: Mild (Child-Pugh A), Moderate (Child-Pugh B) or Severe (Child-Pugh C) |
| Pediatric < 0.55 m2 | 150 mg | 100 mg | 100 mg | 100 mg |
| Pediatric 0.55 to < 0.63 m2 | 200 mg | 150 mg | 100 mg | 100 mg |
| Pediatric 0.63 to < 0.75 m2 | 200 mg | 150 mg | 100 mg | 100 mg |
| Pediatric 0.75 to < 0.9 m2 | 250 mg | 200 mg | 150 mg | 100 mg |
| Pediatric 0.9 to < 1.1 m2 | 300 mg | 200 mg | 200 mg | 150 mg |
| Pediatric ≥ 1.1 m2 | 400 mg | 300 mg | 200 mg | 200 mg |
| CP Ph+ CML with Resistance or Intolerance to Prior Therapy Recommended Starting Dose (Once Daily) By Organ Function | ||||
| Pediatric Patients by Separated BSA Band | Normal renal and hepatic function | Renal Impairment: Creatinine clearance 30 to 50 mL/min | Renal Impairment: Creatinine clearance less than 30 mL/min | Hepatic Impairment: Mild (Child-Pugh A), Moderate (Child-Pugh B) or Severe (Child-Pugh C) |
| Pediatric < 0.55 m2 | 200 mg | 150 mg | 100 mg | 100 mg |
| Pediatric 0.55 to < 0.63 m2 | 250 mg | 200 mg | 150 mg | 100 mg |
| Pediatric 0.63 to < 0.75 m2 | 300 mg | 200 mg | 200 mg | 150 mg |
| Pediatric 0.75 to < 0.9 m2 | 350 mg | 250 mg | 200 mg | 150 mg |
| Pediatric 0.9 to < 1.1 m2 | 400 mg | 300 mg | 250 mg | 200 mg |
| Pediatric ≥ 1.1 m2 | 500 mg | 400 mg | 300 mg | 200 mg |
Dosing in liver impairment
Dosage 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 ] . 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 ] . 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.
In pediatric patients, dose adjustments for non-hematologic toxicities can be conducted similarly to adults, however the dose reduction increments may differ. For pediatric patients with BSA <1.1 m 2 , reduce dose by 50 mg initially followed by additional 50 mg increment if the adverse reaction (AR) persists. For pediatric patients with BSA ≥1.1 m 2 or greater, reduce dose similarly to adults.
| Recommended Starting Dosage | |||
|---|---|---|---|
| [see Use in Specific Populations (8.6, 8.7) and Clinical Pharmacology (12.3)]. | |||
| Newly-diagnosed chronic phase Ph+ CML | 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 | |
| [see Use in Specific Populations (8.6, 8.7) and Clinical Pharmacology (12.3)]. | ||||
| Newly-Diagnosed CP Ph+ CML Recommended Starting Dose (Once Daily) By Organ Function | ||||
| Pediatric Patients by Separated BSABSA=Body Surface Area Band | Normal renal and hepatic function | Renal Impairment: Creatinine clearance 30 to 50 mL/min | Renal Impairment: Creatinine clearance less than 30 mL/min | Hepatic Impairment: Mild (Child-Pugh A), Moderate (Child-Pugh B) or Severe (Child-Pugh C) |
| Pediatric < 0.55 m2 | 150 mg | 100 mg | 100 mg | 100 mg |
| Pediatric 0.55 to < 0.63 m2 | 200 mg | 150 mg | 100 mg | 100 mg |
| Pediatric 0.63 to < 0.75 m2 | 200 mg | 150 mg | 100 mg | 100 mg |
| Pediatric 0.75 to < 0.9 m2 | 250 mg | 200 mg | 150 mg | 100 mg |
| Pediatric 0.9 to < 1.1 m2 | 300 mg | 200 mg | 200 mg | 150 mg |
| Pediatric ≥ 1.1 m2 | 400 mg | 300 mg | 200 mg | 200 mg |
| CP Ph+ CML with Resistance or Intolerance to Prior Therapy Recommended Starting Dose (Once Daily) By Organ Function | ||||
| Pediatric Patients by Separated BSA Band | Normal renal and hepatic function | Renal Impairment: Creatinine clearance 30 to 50 mL/min | Renal Impairment: Creatinine clearance less than 30 mL/min | Hepatic Impairment: Mild (Child-Pugh A), Moderate (Child-Pugh B) or Severe (Child-Pugh C) |
| Pediatric < 0.55 m2 | 200 mg | 150 mg | 100 mg | 100 mg |
| Pediatric 0.55 to < 0.63 m2 | 250 mg | 200 mg | 150 mg | 100 mg |
| Pediatric 0.63 to < 0.75 m2 | 300 mg | 200 mg | 200 mg | 150 mg |
| Pediatric 0.75 to < 0.9 m2 | 350 mg | 250 mg | 200 mg | 150 mg |
| Pediatric 0.9 to < 1.1 m2 | 400 mg | 300 mg | 250 mg | 200 mg |
| Pediatric ≥ 1.1 m2 | 500 mg | 400 mg | 300 mg | 200 mg |
Preparation and administration
| Dose | Volume of Applesauce or Yogurt |
| 100 mg | 10 mL (2 teaspoons) |
| 150 mg | 15 mL (3 teaspoons) |
| 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) |
| 450 mg | 40 mL (8 teaspoons) |
| 500 mg | 45 mL (9 teaspoons) |
| 550 mg | 45 mL (9 teaspoons) |
| 600 mg | 50 mL (10 teaspoons) |
Drug interactions
Check bosutinib against a medication listLabel text (3 paragraphs)
7 DRUG INTERACTIONS • Strong and Moderate CYP3A Inhibitors: Avoid concomitant use with BOSULIF. ( 7.1 ) • Strong CYP3A Inducers: Avoid concomitant use with BOSULIF. ( 7.1 ) • Proton Pump Inhibitors: Use short-acting antacids or H2 blockers as an alternative to proton pump inhibitors. ( 7.1 )
7.1 Effect of Other Drugs on BOSULIF Strong or Moderate CYP3A Inhibitors Avoid the concomitant use of strong or moderate CYP3A inhibitors with BOSULIF. Bosutinib is a CYP3A substrate. Concomitant use with a strong or moderate CYP3A inhibitor increases bosutinib C max and AUC [see Clinical Pharmacology (12.3) ] which may increase the risk of toxicities. Strong CYP3A Inducers Avoid the concomitant use of strong CYP3A inducers with BOSULIF. Bosutinib is a CYP3A substrate. Concomitant use with a strong CYP3A inducer decreases bosutinib C max and AUC [see Clinical Pharmacology (12.3) ] which may reduce BOSULIF efficacy.
Proton Pump Inhibitors (PPI) As an alternative to PPIs, use short-acting antacids or H2 blockers and separate dosing by more than 2 hours from BOSULIF dosing. Bosutinib displays pH dependent aqueous solubility, Concomitant use with a PPI decreases bosutinib C max and AUC [see Clinical Pharmacology (12.3) ] which may reduce BOSULIF efficacy.
Contraindications
4 CONTRAINDICATIONS BOSULIF is contraindicated in patients with a history of hypersensitivity to BOSULIF. Reactions have included anaphylaxis [see Adverse Reactions (6.1) ] . Hypersensitivity to BOSULIF. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
DLikelihood score D: Possible uncommon cause of clinically apparent liver injury.
Bosutinib is a dual kinase inhibitor of both the BCR-ABL and Src tyrosine kinases and is used in the therapy of Philadelphia chromosome-positive chronic myelogenous leukemia. Bosutinib therapy is associated with transient elevations in serum aminotransferase and bilirubin levels and rare instances of clinically apparent acute liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, BOSULIF can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies conducted in rats and rabbits, oral administration of bosutinib during organogenesis caused adverse developmental outcomes, including structural abnormalities, embryo-fetal mortality, and alterations to growth at maternal exposures (AUC) as low as 1.2 times the human exposure at the dose of 500 mg/day ( see Data ). Advise pregnant women of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2–4% and 15–20%, respectively. Data Animal Data In a rat fertility and early embryonic development study, bosutinib was administered orally to female rats for approximately 3 to 6 weeks, depending on day of mating (2 weeks prior to cohabitation with untreated breeder males until gestation day [GD] 7).
Increased embryonic resorptions occurred at greater than or equal to 10 mg/kg/day of bosutinib (1.6 and 1.2 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively), and decreased implantations and reduced number of viable embryos at 30 mg/kg/day of bosutinib (3.4 and 2.5 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively). In an embryo-fetal development study conducted in rabbits, bosutinib was administered orally to pregnant animals during the period of organogenesis at doses of 3, 10, and 30 mg/kg/day.
At the maternally-toxic dose of 30 mg/kg/day of bosutinib, there were fetal anomalies (fused sternebrae, and 2 fetuses had various visceral observations), and an approximate 6% decrease in fetal body weight. The dose of 30 mg/kg/day resulted in exposures (AUC) approximately 5.1 and 3.8 times the human exposures at the recommended doses of 400 and 500 mg/day, respectively. Fetal exposure to bosutinib-derived radioactivity during pregnancy was demonstrated in a placental-transfer study in pregnant rats.
In a rat pre- and postnatal development study, bosutinib was administered orally to pregnant animals during the period of organogenesis through lactation day 20 at doses of 10, 30, and 70 mg/kg/day.…
Breastfeeding (LactMed)
No information is available on the clinical use of bosutinib during breastfeeding. Because bosutinib is 96% bound to plasma proteins, the amount in milk is likely to be low. However, its half-life is about 22 hours and it might accumulate in the infant. National Comprehensive Cancer Network guidelines recommend avoiding breastfeeding during bosutinib therapy and the manufacturer recommends withholding breastfeeding until 2 weeks following the last dose.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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