Must-read for patients: An overview of the basic information in the instructions for use of bosutinib

1. Generic name: Bosutinib

Product name:BOSULIF

Other Names:Bosutinib, bosutinib, bosutinib, bosutinib, posutinib

2. Indications:

Bosutinib (Bosutinib) is indicated for the treatment of the following adult patients:

1. Newly diagnosed chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+CML);

2. People aged 1 year and above suffer from chronic phase, accelerated phase (AP) or blast phase (BP) Ph+CML, or are resistant or intolerant to previous treatments.

3. Usage and dosage:

1. Recommended dose: The recommended dose of bosutinib is to be taken orally once daily with a meal. Tablets should be swallowed whole and not broken or cut. Treat until disease progression or intolerance to treatment. If a dose is missed by more than 12 hours, the patient should skip the dose and take the usual prescribed dose the next day.

(1) Newly diagnosed CP Ph+CML:The recommended dose of bosutinib is 400 mg once daily, taken orally with food.

(2) CP, AP or BP Ph+CML, or resistance or intolerance to previous treatment:The recommended dose of bosutinib is 500 mg once daily, taken orally with food.

2. Dose escalation: In clinical studies in adult Ph+CML patients, for patients who do not achieve or maintain a hematological, cytogenetic or molecular response and who do not experience grade 3 or higher adverse reactions at the recommended starting dose, the dose is allowed to be increased in increments of 100 mg once daily to a maximum of 600 mg once daily.

3. Dose adjustment: If patients experience adverse reactions during treatment with bosutinib, doctors usually adjust the drug dosage.

(1) Hepatic transaminase elevation: If the hepatic transaminase elevation exceeds 5 times the institutional upper limit of normal (ULN), discontinue bosutinib until recovery to ≤2.5 times ULN, and thereafter continue 400 mg once daily. If recovery takes longer than 4 weeks, discontinue bosutinib. If transaminases are elevated ≥3 times ULN, bilirubin is elevated >2 times ULN and alkaline phosphatase is <2 times ULN, discontinue bosutinib.

(2) Diarrhea: For grade 3-4 diarrhea (increased stool frequency by ≥7 times per day compared with baseline/before treatment), stop bosutinib until it returns to grade 1. Bosutinib can be resumed at a dose of 400mg once daily.

(3) For other clinically significant moderate or severe non-hematologic toxicities, withhold bosutinib until toxicity resolves and then consider dose reduction to 100 mg once daily. If clinically appropriate, consider titrating the dose back to the once-daily starting dose.

(4) Myelosuppression:For patients with platelets <50000×106/L, bosutinib should be discontinued. If recovery occurs within 2 weeks, treatment with the same dose of bosutinib should be continued. If blood cell counts remain low for more than 2 weeks, after recovery, reduce the dose by 100 mg and continue treatment. If cytopenias recur, after recovery, reduce the dose by an additional 100 mg and continue treatment in patients using a dose <300 mg/day.

(5) Renal function impairment:For creatinine clearance30-50mL/min ofnewly diagnosedCP For Ph+CML patients, the dose is adjusted to 300 mg daily; for patients with CP, AP or BP Ph+CML, or patients with resistance or intolerance to previous treatment, the dose is adjusted to 400 mg daily. For creatinine clearanceless than30mL/min Newly diagnosedCP Ph+CML patients, adjust dose to 200 mg daily; CP, AP or BP Ph+CML, or patients with resistance or intolerance to previous treatment, the dose is adjusted to 300mg daily.

（6) Liver function impairment: including mild (Child-Pugh A), moderate (Child-Pugh B) or severe (Child-Pugh C), regardless of type, patients should adjust the dose to 200 mg daily.

4. Adverse reactions:

In clinical studies of bosutinib, inAmong ≥20% of newly diagnosed CP Ph+CML or CP, AP, or BP Ph+ CML patients who are resistant or intolerant to previous treatment, the most common adverse reactions are diarrhea, rash, nausea, abdominal pain, vomiting, fatigue, liver dysfunction, and respiratory tract infection; the most common laboratory abnormalities (≥20%) are increased creatinine, decreased hemoglobin, decreased lymphocyte count, decreased platelet, increased ALT, decreased calcium, decreased white blood cell count, decreased absolute neutrophil count, and increased AST. After bosutinib was launched, adverse events such as thrombotic microangiopathy and Stevens-Johnson syndrome also occurred.

5. Storage:

Bosutinib will be stored at 20°C to 25°C (68°F to 77°F); tolerance allowed is 15°C to 30°C (59°F to 86°F). Avoid touching or handling crushed or broken tablets. Any unused product or waste should be disposed of in accordance with local requirements or pharmaceutical take-back programs.

6. Taboo:

Bosutinib is contraindicated in patients with a history of hypersensitivity to Bosutinib, including anaphylaxis.

7. Mechanism of action:

Bosutinib is a TKI. Bosutinib inhibits the BCR-ABL kinase that promotes chronic myelogenous leukemia; it is also an inhibitor of Src family kinases including Src, Lyn, and Hck. Bosutinib inhibits 16 of 18 imatinib-resistant forms of BCR-ABL kinase expressed in murine myeloid cell lines. Bosutinib does not inhibit T315I and V299L mutant cells.

8. Special groups:

1. Women: According to animal studies, bosutinib taken by pregnant women can cause harm to the fetus. It is therefore recommended that females of childbearing potential use an effective method of contraception (a method that results in a pregnancy rate of less than 1%) during treatment with the drug and for at least 2 weeks after the last dose; breastfeeding is not recommended during treatment with the drug and for at least 2 weeks after the last dose.