boe-SUE-ti nib

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

• Chronic/accelerated/blast phase Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) that it resistant/intolerant to previous therapies.
• Newly diagnosed chronic phase Ph+ CML.

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

• Decreased progression of CML.

Absorption: Absorbed following oral administration.

Distribution: Unknown.

Protein Binding: 96%.

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

Half-life: 22.5 hr.

(beneficial hematologic response)

Contraindicated in:

• Hypersensitivity
• Concurrent use of moderate to strong CYP3A4 inhibitors or inducers (may significantly alter drug effects)
• OB: Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

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

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

Derm: STEVENS-JOHNSON SYNDROME, itching, rash, acne.

EENT: tinnitus.

Endo: hypothyroidism.

F and E: dehydration, hyperkalemia.

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

GU: ↓fertility, renal impairment.

Hemat: anemia, neutropenia, thrombocytopenia.

MS: arthralgia, back pain, myalgia.

Neuro: dizziness, fatigue, headache, dysgeusia.

Resp: cough, pulmonary edema.

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), fever.

Drug-Drug:

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

Drug-Natural Products:

• Concurrent use with St. John's wort may ↓ blood levels and beneficial effects and should be avoided.

Drug-Food:

• Grapefruit juice may ↑ blood levels and the risk of toxicity and should be avoided.

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

• PO (Adults): 500 mg once daily, if complete hematologic response has not occurred by 8 wk, or complete cytologic response by 12 wk or there has been no occurrence of Grade 3 adverse reactions, consider ↑ dose to 600 mg once daily. Continue until disease progression or unacceptable toxicity.

Newly Diagnosis Ph+ CML

• PO (Adults): 400 mg once daily, if complete hematologic response has not occurred by 8 wk, or complete cytologic response by 12 wk or 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.

• Tablets: 100 mg; 400 mg; 500 mg;

• Monitor for diarrhea, nausea, vomiting, and abdominal pain. Usually occurs within 4 days of therapy and lasts for about 3 days. For Grade 3–4 diarrhea (↑ of 7 stools/day over baseline/pretreatment), hold bosutinib until recovery to Grade 1.
• Assess for signs and symptoms fluid retention (swelling in hands, ankles, or feet; weight gain; shortness of breath; cough; chest pain). May manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Interrupt, reduce dose or discontinue bosutinib as necessary.
• Monitor for signs of allergic reaction (rash, shortness of breath, respiratory tract infections, loss of appetite, headache, dizziness, back pain, joint pain, itching).
• Assess patient for skin rash frequently during therapy. Discontinue bosutinib at first sign of rash; may be life-threatening. Stevens-Johnson syndrome may develop. Treat symptomatically; may recur once treatment is stopped.
• Monitor for signs and symptoms of cardiac failure (shortness of breath; weight gain; swelling in hands, ankles or feet.) Interrupt therapy, reduce dose, or discontinue therapy as needed.

• Verify negative pregnancy test prior to starting therapy.Monitor CBC weekly for first mo, then monthly thereafter. May cause thrombocytopenia, anemia, and neutropenia. If ANC <1000 × 10⁶/L or platelets <50,000 × 10⁶/L, withhold bosutinib until ANC 1000 × 10⁶/L and platelets 50,000 × 10⁶/L. Resume treatment with bosutinib at same dose if recovery occurs within 2 weeks. If blood counts remain low for >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.
  • Monitor hepatic function monthly for first 3 mo, then periodically during therapy as clinically indicated. If ↑ liver transaminases >5 × institutional upper limit of normal (ULN) occur, hold bosutinib until recovery to 2.5 × ULN and resume at 400 mg once daily thereafter. If recovery takes longer than 4 weeks, discontinue bosutinib. If transaminase ↑3 × ULN occur concurrently with bilirubin ↑ >2 × ULN and alkaline phosphatase <2 × ULN, discontinue bosutinib.
  • Monitor renal function prior to and periodically during therapy, especially in patients with pre-existing renal dysfunction and other risk factors. May require dose adjustments.

• PO: Administer once daily with food. In patients who do not reach complete hematological response by wk 8 or a complete cytogenetic response by wk 12, who did not have Grade 3 or higher adverse reactions, and who are currently taking 500 mg daily, consider dose escalation to 600 mg once daily with food. DNC: Swallow tablets whole; do not crush, break or chew. Do not handle crushed or broken tablets.

• Instruct patient to take bosutinib as directed. Take missed doses as soon as remembered if within 12 hours, if longer than 12 hrs 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 your 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, abdominal pain occur.
• Inform patient to take medications that decrease stomach acid (antacids and H₂ blockers) 2 hrs before or 2 hrs after bosutinib and to consult health care professional if taking a proton pump inhibitor (PPI).
• 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.
• Rep: 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.

• Decreased progression of CML.

Bosulif

NDC Code^*

• 0069- Pfizer Laboratories Div Pfizer Inc
  • 0069-0135- BOSULIF
    • 0069-0135-01- 120 TABLET, FILM COATED in 1 BOTTLE (0069-0135-01)

• 0069- Pfizer Laboratories Div Pfizer Inc
  • 0069-0136- BOSULIF
    • 0069-0136-01- 30 TABLET, FILM COATED in 1 BOTTLE (0069-0136-01)

• 0069- Pfizer Laboratories Div Pfizer Inc
  • 0069-0193- BOSULIF
    • 0069-0193-01- 30 TABLET, FILM COATED in 1 BOTTLE (0069-0193-01)

• 63539- U.S. Pharmaceuticals
  • 63539-117- BOSULIF
    • 63539-117-01- 120 TABLET, FILM COATED in 1 BOTTLE (63539-117-01)