Genetic Implications: Genetic Implications

boe-sue-ti nib

Trade Name(s)

  • Bosulif

Ther. Class.

Pharm. Class.
kinase inhibitors


Genetic implication Treatment of adults with chronic/accelerated/blast phase Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia that it resistant/intolerant to previous therapies.


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

Therapeutic Effect(s):

Decreased progression of CML.


Absorption: Absorbed following oral administration

Distribution: Unknown.

Protein Binding: 96%

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

Half-life: 22.5 hr

TIME/ACTION PROFILE (beneficial hematologic response)

POwithin 8–12 wk4–6 hr (blood level)9–18 mo or longer


Contraindicated in:

  • Hypersensitivity;
  • Lactation: Breastfeeding should be avoided;
  • OB:  Pregnancy (may cause fetal harm);
  • Concurrent use of moderate to strong CYP3A4 inhibitors/inducers or P-gp inhibitors (may significantly alter drug effects).

Use Cautiously in:

  • Hepatic impairment (dose ↓ recommended);
  • Renal impairment (dose ↓ recommended);
  • OB:  Patients with reproductive potential (effective contraception is recommended);
  • Pedi:  Safety and effectiveness not established.

Adverse Reactions/Side Effects

CNS: dizziness, fatigue, headache

EENT: tinnitus

Resp: cough

CV: chest pain, fluid retention, pericarditis, QT interval prolongation

GI: abdominal pain, ↓ appetite, diarrhea, nausea, vomiting, dysgeusia, gastritis, GI bleeding, hepatic toxicity, pancreatitis

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

F and E: dehydration, hyperkalemia

GU: renal impairment

Hemat: anemia, neutropenia, thrombocytopenia

MS: arthralgia, back pain, myalgia

Misc: allergic reactions including anaphylaxis, fever

* CAPITALS indicate life-threatening.
Underline indicate most frequent.



Drug-Natural Products:

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


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


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 treatment until disease progression or patient intolerance. .

Renal Impairment 
PO (Adults):  CCr 30–50 mL/min– 400 mg once daily;  CCr <30 mL/min– 300 mg once daily.Hepatic Impairment 
PO (Adults):  Any degree of hepatic impairment– 200 mg once daily.


Tablets: 100 mg, 500 mg


  • Monitor for diarrhea, nausea, vomiting, and abdominal pain. For Grade 3–4 diarrhea (↑ of ≥7 stools/day over baseline/pretreatment), withhold 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.

Lab Test Considerations:

Monitor CBC weekly for first mo, then monthly thereafter. May cause thrombocytopenia, anemia, and neutropenia. If ANC <1000 x 106 /L or platelets <50,000 x 106 /L, withhold bosutinib until ANC ≥1000 x 106 /L and platelets ≥50,000 x 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, withhold 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.

Potential Diagnoses


  • 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. Swallow tablets whole; do not crush, break or chew. Do not handle crushed or broken tablets.

Patient/Family Teaching

  • 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 (cimetidine (Tagamet), famotidine (Pepcid), ranitidine (Zantac), aluminum hydroxide/magnesium hydroxide (Maalox), calcium carbonate (Tums), calcium carbonate and magnesia (Rolaids) 2 hrs before or 2 hrs after bosutinib and to avoid taking esomeprazole (Nexium), esomeprazole strontium, dexlansoprazole (Dexilant), lansoprazole (Prevacid), omeprazole (Prilosec, Vimovo, Zegerid), pantoprazole sodium (Protonix), and rabeprazole (AcipHex).
  • 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.
  • Rep:  Caution female patient to use effective contraception during and for at least 30 days following discontinuation of therapy. Advise patient to avoid pregnancy and breastfeeding; notify health care professional immediately if pregnancy is suspected.

Evaluation/Desired Outcomes

Decreased progression of CML.

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