Bosulif

— THERAPEUTIC CATEGORIES —
  • Leukemias, lymphomas, and other hematologic cancers
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Bosulif Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Bosutinib 100mg, 400mg, 500mg; tabs.

    Pharmacological Class

    Tyrosine kinase inhibitor.

    How Supplied

    Tabs 100mg—120; 400mg, 500mg—30

    Manufacturer

    Pfizer Inc.

    Generic Availability

    NO

    Mechanism of Action

    Bosutinib inhibits the Bcr-Abl kinase that promotes CML; it is also an inhibitor of Src-family kinases including Src, Lyn, and Hck.

    Bosulif Indications

    Indications

    Newly-diagnosed chronic phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML). Chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.

    Bosulif Dosage and Administration

    Adult

    Take with food. Swallow whole. Continue until disease progression or patient intolerance. Newly-diagnosed: 400mg once daily. Renal impairment (CrCl 30–50mL/min): initially 300mg daily; (CrCl <30mL/min): initially 200mg daily. With resistance/intolerance to prior therapy: 500mg once daily. Renal impairment (CrCl 30–50mL/min): initially 400mg daily; (CrCl <30mL/min): initially 300mg daily. Both: hepatic impairment: initially 200mg daily. Dose escalation or dose adjustments for toxicity: see full labeling.

    Children

    <18yrs: not established.

    Administration

    Take with food. If dose is missed beyond 12hrs, skip dose and take the usual dose on the following day.

    Nursing Considerations

    Take with food. If dose is missed beyond 12hrs, skip dose and take the usual dose on the following day. Contraceptive measures to prevent pregnancy should be used during and for at least 30 days after completing treatment.

    Bosulif Contraindications

    Not Applicable

    Bosulif Boxed Warnings

    Not Applicable

    Bosulif Warnings/Precautions

    Warnings/Precautions

    Monitor and manage GI toxicity, cardiac failure/ischemia, fluid retention; withhold, reduce dose, or discontinue as necessary. Coronary artery disease risk factors (including history of diabetes, BMI >30, hypertension, vascular disorders): higher occurrence of cardiac ischemic events. Perform CBC weekly for first month, then monthly; hepatic enzyme tests monthly for first 3 months (more frequently if transaminase elevations occur); withhold, reduce dose, or discontinue as necessary. Monitor renal function at baseline and during therapy; consider adjusting dose if renal impairment occurs. Dialysis: not studied. Embryo-fetal toxicity. Pregnancy: exclude status prior to initiation. Advise females of reproductive potential to use effective contraception during and for ≥2 weeks after the last dose. Nursing mothers: not recommended (during and for ≥2 weeks after the last dose).

    Bosulif Pharmacokinetics

    Absorption

    • Following administration of a single oral dose of Bosulif 500 mg with food in patients with CML, the median (minimum, maximum) time-to-peak concentration (tmax) was 6.0 (6.0, 6.0) hours. The absolute bioavailability was 34% in healthy subjects.

    • Effect of Food:

      • When given with a high fat meal in healthy subjects, oral bosutinib Cmax increased 1.8-fold and AUC increased 1.7-fold. The high-fat meal (800-1000 total calories) consisted of approximately 150 protein calories, 250 carbohydrate calories, and 500-600 fat calories.

    Distribution

    • Mean volume of distribution (SD): 2441 (796) L in healthy subjects; 6080 (1230) L in patients with CML.

    • Protein binding is 94% in vitro and 96% ex vivo.

    Metabolism

    • Hepatic (CYP3A4).

    Elimination

    • Fecal (91.3%), renal (3.3%). 

    • Mean half-life (SD): 22.5 (1.7) hours. Mean clearance (SD): 189 (48) L/h.

    Bosulif Interactions

    Interactions

    Potentiated by strong or moderate CYP3A inhibitors (eg, ketoconazole, aprepitant, grapefruit products); avoid concomitant use. Antagonized by strong CYP3A inducers (eg, rifampin, St. John’s wort); avoid concomitant use. Antagonized by proton pump inhibitors (eg, lansoprazole); consider short-acting antacids or H2 blockers instead; separate dosing by >2hrs.

    Bosulif Adverse Reactions

    Adverse Reactions

    Diarrhea, rash, nausea, abdominal pain, vomiting, fatigue, hepatic dysfunction, respiratory tract infection, pyrexia, headache, lab abnormalities; myelosuppression, pneumonia, pleural effusion, coronary artery disease, gastroenteritis.

    Bosulif Clinical Trials

    See Literature

    Bosulif Note

    Not Applicable

    Bosulif Patient Counseling

    See Literature

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