bosutinib (Rx)

Brand and Other Names:Bosulif
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Dosing & Uses


Dosage Forms & Strengths


  • 100mg
  • 500mg

Chronic Myelogenous Leukemia

Indicated for chronic, accelerated, or blast phase Philadelphia chromosome positive chronic myelogenous leukemia (CML) in patients resistant to or intolerant to other therapies, including imatinib

500 mg PO qDay with food

May increase dose to 600 mg qDay if complete hematological response is not achieved by week 8 or a complete cytogenetic response by week 12; dose escalation only if adverse reactions grade 2 or lower and patient taking 500 mg/day dose

Dosage Modifications

Renal impairment

  • Pre-existing severe renal impairment (CrCl <30 mL/min): 300 mg PO qDay
  • For patients with CrCl 30-50 mL/min who cannot tolerate a 400 mg dose, follow dose adjustment recommendations for toxicity In a dedicated renal impairment trial, compared to volunteers with normal renal function, the exposure (AUC) of bosutinib increased by 60% and 35% in subjects with CrCL <30 mL/min and CrCL 30-50 mL/min, respectively

Hepatic impairment

  • Pre-existing mild, moderate, and severe hepatic impairment: 200 mg PO qDay
  • 200 mg/day in hepatic impairment is predicted to result in AUC similar to 500 mg/day in normal hepatic function; however, there are no clinical data for efficacy of 200 mg/day in patients with hepatic impairment and CML


  • If liver transaminases greater than 5 xULN occur, hold dosing until recovery to ≤2.5 x ULN and resume at 400 mg qDay thereafter; discontinue if recovery takes longer than 4 weeks
  • Discontinue if transaminase elevations ≥3 xULN occur concurrently with bilirubin elevations >2 xULN and alkaline phosphatase <2 x ULN (Hy’s law case definition)


  • NCI CTCAE Grade 3-4 diarrhea (≥7 stools/day over baseline/pretreatment): Hold dosing until recovery to Grade ≤1; may resume dose at 400 mg qDay

Other nonhematologic toxicities

  • Withhold dose until toxicity resolved, and then consider resuming at 400 mg qDay
  • If clinically appropriate, consider re-escalating the dose to 500 mg qDay


  • ANC <1000 x10^6/L or platelets <50,000 x10^6/L: Withhold dose until ANC ≥1000x10^6/L and platelets ≥50,000x10^6/L
  • Resume treatment with 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 <300 mg/day have not been evaluated

Coadministration with CYP3A and/or P-gp inhibitors

  • Strong or moderate CYP3A and/or P-gp inhibitors: Avoid concomitant use; increase bosutinib plasma concentration expected and possible increased risk for toxicities
  • Concomitant ketoconazole (strong CYP3A inhibitor) increased bosutinib Cmax 5.2-fold and AUC 8.6-fold compared to bosutinib alone

Coadministration with CYP3A inducers

  • Strong or moderate CYP3A inducers: Avoid concomitant use; large reduction in exposure to bosutinib expected
  • Coadministration with rifampin (strong inducer) decreased bosutinib Cmax by 86% and AUC by 94% compared to bosutinib alone


Take with food

Swallow table whole, do not chew, crush, or cut

Medications that neutralize stomach acid (eg, H2 antagonists, antacids) may be taken 2 hr before or after bosutinib

Bosutinib displays pH-dependent aqueous solubility, avoid PPIs because of long-term gastric acid suppression

<18 years: Safety and efficacy not established



Interaction Checker

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            Adverse Effects


            Diarrhea (82%)

            Nausea (46%)

            Thrombocytopenia, all grades (41%)

            Vomiting (39%)

            Abdominal pain (37%)

            Rash (35%)

            Thrombocytopenia, grades 3/4 (33%)

            Anemia (27%)

            Pyrexia (26%)

            Fatigue (24%)

            Neutropenia (23%)

            Headache (20%)

            Cough (20%)

            Anemia (19%)

            Neutropenia (17%)

            Increased ALT (17%)

            Increased AST (14%)

            Edema (14%)

            Arthralgia (14%)

            Decreased appetite (13%)

            Respiratory tract infection (12%)

            Dyspnea (12%)

            Asthenia (11%)

            Back pain (11%)


            Nasopharyngitis (10%)

            Dizziness (10%)

            Pruritus (10%)

            SGPT/ALT >5 xULN (9%)

            Lipase >2 xULN (7%)

            Phosphorus <0.6 mmol/L (7%)

            SGOT/AST >5 xULN (4%)

            Total bilirubin >3 xULN (1%)

            Febrile neutropenia

            Pericardial effusion



            Chest pain



            Anormal hepatic function

            Drug hypersensitivity

            Pneumoniae, influenza, bronchitis

            Electrocardiogram QT prolonged

            Increased blood CPK

            Increased blood creatinine





            Renal failure

            Pleural effusion

            Urticaria, pruritus




            Acute pancreatitis

            GI hemorrhage

            Liver injury

            Anaphylactic shock

            Acute pulmonary edema

            Respiratory failure

            Pulmonary hypertension

            Erythema multiforme

            Exfoliative rash

            Drug eruption

            Postmarketing Reports


            Steven's Johnson Syndrome






            See Dosage Modifications regarding withholding, decreasing, or discontinuing bosutinib treatment with various toxicities

            Diarrhea, nausea, vomiting, and abdominal pain may occur

            Thrombocytopenia, anemia, and neutropenia occur with treatment; perform CBC weekly for first month and then monthly thereafter, or as clinically indicated

            Elevated ALT, AST, and/or bilirubin may occur; perform monthly hepatic enzyme tests for first 3 months during treatment, and then as clinically indicated

            Fluid retention may occur and manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema

            Drugs that may increase bosutinib plasma levels: CYP3A or P-glycoprotein (P-gp) inhibitors

            Drugs that may decrease bosutinib plasma concentrations: CYP3A inducers, proton pump inhibitors

            Bosutinib altering plasma concentrations of drugs: Increases P-gp substrates

            Decline in glomerular filtration rate reported in patients receiving therapy, which in turn increases bosutinib exposure in patients; use caution in patients with moderate renal impairment; dosage adjustment recommended

            Hepatic impairment increases exposure to bosutinib in patients with hepatic impairment; consider decreasing the dose

            Use caution in patients with a prior history of pancreatitis; acute pancreatitis reported with use

            Monitor closely patients at risk for bleeding episodes (eg, coagulation disorders); bleeding events reported

            Bone fracture and mineral abnormalities, including hypophosphatemia reported; monitor patients with severe osteoporosis or endocrine disease, including hyperparathyroidism; monitor bone density and/or mineral abnormalities

            Advise females of reproductive potential to use effective contraceptive measures to prevent pregnancy while on therapy


            Pregnancy & Lactation

            Pregnancy Category: D; Based on mechanism of action and findings in animals, can cause fetal harm when administered to a pregnant woman

            Lactation: Unknown whether distributed in breast milk; a decision should be made whether to discontinue nursing or to discontinue the drug

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.



            Mechanism of Action

            Tyrosine kinase inhibitor; Inhibits Bcr-Abl kinase that promotes CML; also inhibits SRc-family kinases including Src, Lyn, and Hck

            Bosutinib inhibited 16 of 18 imatinib-resistant forms of Bcr-Abl expressed in murine myeloid cell lines, but did not inhibit T315I and V299L mutant cells


            Absolute bioavailability: 34% (healthy volunteers with food)

            Peak Plasma Time: 4-6 hr

            Peak Plasma Concentration: 200 ng/mL (with food at day15); increased 1.8-fold with high fat meal

            AUC: 3650 ng•h/mL (with food at day 15); increased 1.7-fold with high fat meal


            Protein Bound: 94-96%

            Vd: 6,080 L

            P-gp substrate and inhibitor


            Metabolized by in liver primarily by CYP3A4

            Metabolites (inactive): Oxydechlorinated (M2) bosutinib (19% of parent exposure) and N-desmethylated (M5) bosutinib (25% of parent exposure), with bosutinib N-oxide (M6) as a minor circulating metabolite


            Half-life (terminal phase): 22.5 hr

            Total body clearance: 189 L/hr

            Excretion: 91.3% feces; 3% urine





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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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