• Chronic phase Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) that is newly diagnosed or resistant/intolerant to previous therapies.
• Accelerated/blast phase Ph+ CML that is resistant/intolerant to previous therapies.

Contraindicated in:

• Hypersensitivity
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Renal impairment (dose ↓ recommended)
• Hepatic impairment (dose ↓ recommended)
• Women of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: chest pain, HF, myocardial ischemia, pericardial effusion, pericarditis, peripheral edema, QT interval prolongation, tachycardia.

Derm: itching, rash, acne, STEVENS-JOHNSON SYNDROME (SJS).

EENT: tinnitus.

Endo: hypothyroidism.

F and E: dehydration, hyperkalemia.

GI: ↑liver enzymes, abdominal pain, diarrhea, nausea, vomiting, gastritis, GI bleeding, HEPATOTOXICITY, pancreatitis.

GU: ↓fertility, renal impairment.

Hemat: anemia, neutropenia, thrombocytopenia.

Metab: ↓appetite.

MS: arthralgia, back pain, myalgia.

Neuro: dizziness, fatigue, headache, dysgeusia.

Resp: cough, pulmonary edema.
Misc: fever, (INCLUDING ANAPHYLAXIS)HYPERSENSITIVITY REACTIONS .

Drug-Drug:

• Moderate or strong CYP3A4 inhibitors, including aprepitant, atazanavir, ciprofloxacin, clarithromycin, conivaptan, crizotinib, darunavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, verapamil, and voriconazole, ↑ levels and risk of toxicity; avoid concurrent use.
• Moderate or strong CYP3A4 inducers, including bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenobarbital, phenytoin, rifabutin, and rifampin, may ↓ levels and effectiveness; avoid concurrent use.
• Proton pump inhibitors, including esomeprazole, dexlansoprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole, may ↓ levels and effectiveness; avoid concurrent use. Consider using short-acting antacids or histamine-H₂ receptor blockers instead (these should be taken 2 hr before or after bosutinib).
• May ↑ digoxin levels and risk of toxicity.

Drug-Natural Products:

• St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

• Grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent use.

• Capsules: 50 mg; 100 mg;
• Tablets: 100 mg; 400 mg; 500 mg;

Chronic Phase Ph+ CML Resistant/Intolerant to Previous Therapies

• PO (Adults and Children 1 yr and BSA 1.1 m²): 500 mg once daily; if hematologic, cytogenetic, or molecular response is not achieved or maintained and there has been no occurrence of Grade 3 adverse reactions, consider ↑ dose in 100-mg/day increments up to maximum dose of 600 mg once daily. Continue until disease progression or unacceptable toxicity.
• PO (Children 1 yr and BSA 0.9–<1.1 m²): 400 mg once daily; if hematologic, cytogenetic, or molecular response is not achieved after 3 mo, consider ↑ dose in 50-mg/day increments up to maximum dose of 500 mg once daily. Continue until disease progression or unacceptable toxicity.
• PO (Children 1 yr and BSA 0.75–<0.9 m²): 350 mg once daily; if hematologic, cytogenetic, or molecular response is not achieved after 3 mo, consider ↑ dose in 50-mg/day increments up to maximum dose of 450 mg once daily. Continue until disease progression or unacceptable toxicity.
• PO (Children 1 yr and BSA 0.63–<0.75 m²): 300 mg once daily; if hematologic, cytogenetic, or molecular response is not achieved after 3 mo, consider ↑ dose in 50-mg/day increments up to maximum dose of 400 mg once daily. Continue until disease progression or unacceptable toxicity.
• PO (Children 1 yr and BSA 0.55–<0.63 m²): 250 mg once daily; if hematologic, cytogenetic, or molecular response is not achieved after 3 mo, consider ↑ dose in 50-mg/day increments up to maximum dose of 350 mg once daily. Continue until disease progression or unacceptable toxicity.
• PO (Children 1 yr and BSA <0.55 m²): 200 mg once daily; if hematologic, cytogenetic, or molecular response is not achieved after 3 mo, consider ↑ dose in 50-mg/day increments up to maximum dose of 300 mg once daily. Continue until disease progression or unacceptable toxicity.

Newly Diagnosed Chronic Phase Ph+ CML

• PO (Adults and Children 1 yr and BSA 1.1 m²): 400 mg once daily; if hematologic, cytogenetic, or molecular response is not achieved or maintained and there has been no occurrence of Grade 3 adverse reactions, consider ↑ dose in 100-mg/day increments up to maximum dose of 600 mg once daily. Continue until disease progression or unacceptable toxicity.
• PO (Children 1 yr and BSA 0.9–<1.1 m²): 300 mg once daily; if hematologic, cytogenetic, or molecular response is not achieved after 3 mo, consider ↑ dose in 50-mg/day increments up to maximum dose of 400 mg once daily. Continue until disease progression or unacceptable toxicity.
• PO (Children 1 yr and BSA 0.75–<0.9 m²): 250 mg once daily; if hematologic, cytogenetic, or molecular response is not achieved after 3 mo, consider ↑ dose in 50-mg/day increments up to maximum dose of 350 mg once daily. Continue until disease progression or unacceptable toxicity.
• PO (Children 1 yr and BSA 0.55–<0.75 m²): 200 mg once daily; if hematologic, cytogenetic, or molecular response is not achieved after 3 mo, consider ↑ dose in 50-mg/day increments up to maximum dose of 300 mg once daily. Continue until disease progression or unacceptable toxicity.
• PO (Children 1 yr and BSA <0.55 m²): 150 mg once daily; if hematologic, cytogenetic, or molecular response is not achieved after 3 mo, consider ↑ dose in 50-mg/day increments up to maximum dose of 250 mg once daily. Continue until disease progression or unacceptable toxicity.

Accelerated/Blast Phase Ph+ CML Resistant/Intolerant to Previous Therapies

• PO (Adults): 500 mg once daily; if hematologic, cytogenetic, or molecular response is not achieved or maintained and there has been no occurrence of Grade 3 adverse reactions, consider ↑ dose in 100-mg/day increments up to maximum dose of 600 mg once daily. Continue until disease progression or unacceptable toxicity.

Bosulif

• Acts as a kinase inhibitor, specifically inhibiting the kinase that promotes CML.

• Decreased progression of CML.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Absorption: 34% absorbed following oral administration; absorption ↑ with high-fat meal.

Distribution: Extensively distributed to tissues.

Protein Binding: 96%.

Metabolism/Excretion: Mostly metabolized, mainly by the CYP3A4 isoenzyme; metabolites do not have antineoplastic activity.

Half-life: 22.5 hr.

(beneficial hematologic response)

• Instruct patient to take bosutinib as directed. Take missed doses as soon as remembered if within 12 hr; if longer than 12 hr, skip dose and take usual prescribed dose on the following day. Do not stop taking bosutinib without consulting health care professional. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
• Advise patient to avoid grapefruit and grapefruit juice during therapy.
• Advise patient to immediately report fever, jaundice (skin or the white part of the eyes turns yellow or dark “tea color” urine), symptoms of infection, fluid retention, anaphylaxis, rash, unexpected bleeding or bruising, or blood in urine or stools occur. Advise patient to notify health care professional if diarrhea, nausea, vomiting, or abdominal pain occur.
• Inform patient to take medications that ↓ stomach acid (antacids and H₂ blockers) 2 hr before or 2 hr after bosutinib and to consult health care professional if taking a proton pump inhibitor.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
• May cause fetal harm. Advise females of reproductive potential to use effective contraception and to avoid breastfeeding during and for at least 2 wk after last dose of therapy. Advise patient to notify health care professional immediately if pregnancy is suspected. May impair fertility in male and female patients.

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