Bosutinib

530.45

530.45

1308068-626-2

5018V4AEZ0

C60809

L01XE14|L - Antineoplastic and immunomodulating agents

29335990

82.9

5.4

off-white to light brown

1.4±0.1 g/cm3

116-120 °C

649.7±55.0°C at 760 mmHg

346.7±31.5 °C

1.652

DMSO: ≥15mg/mL

room temp

NONH for all modes of transport

3

36

26

Xi

P305 + P351 + P338

H319-H413

Most common adverse reactions (incidence greater than 20%) are diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue. Because bosutinib is not an inhibitor of c-KIT or PDGF receptor, it has less hematologic toxicities.

In large clinical trials of bosutinib, elevations in serum aminotransferase levels were common, occurring in up to 58% of bosutinib treated patients. Values greater than 5 times the upper limit of normal (ULN) occurred in 4% to 19% of bosutinib recipients (and 3% of imatinib treated subjects). These abnormalities were usually asymptomatic, but led to discontinuation of therapy in up to 2% of treated patients. In addition, there have been isolated reports of clinically apparent liver injury attributed to bosutinib therapy, although the frequency of this outcome and the clinical features of the injury have not been well defined. The time to onset has generally been within 3 months and the pattern of serum enzyme elevations was usually hepatocellular.

94% bound to human plasma proteins in vitro. 96% bound to human plasma proteins in healthy subjects ex vivo. Extent of protein binding is not concentration-dependent.

Treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy in adult patients.|FDA Label|Bosulif is indicated for the treatment of adult patients with:newly‑diagnosed chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukaemia (Ph+ CML).CP, accelerated phase (AP), and blast phase (BP) Ph+ CML previously treated with one or more tyrosine kinase inhibitor(s) [TKI(s)] and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.|Treatment of chronic myeloid leukaemia (CML)|Drug: Bosutinib

Bosutinib is a dual kinase inhibitor of both the BCR-ABL and Src tyrosine kinases and is used in the therapy of Philadelphia chromosome-positive chronic myelogenous leukemia. Bosutinib therapy is associated with transient elevations in serum aminotransferase and bilirubin levels and rare instances of clinically apparent acute liver injury.

Antineoplastic Agents

Food increase the exposure of bosutinib. Tmax, single dose, cancer patients, fed-state = 4-6 hours; After 15 daily doses of bosutinib 500 mg with food in CML patients, the pharmacokinetic parameters are as follows: Cmax = 200 ng/mL; AUC = 3650 ng∙h/mL|When given a single oral dose, 91.3% of the dose was recovered in feces and 3% of the dose recovered in urine.|Apparent volume of distribution = 6080 ± 1230 L.|Mean clearance (CL/F), single oral dose, fed-state = 189 L/h

Bosutinib is primarily metabolized by CYP3A4. The major circulating metabolites identified in plasma are 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. All the metabolites were deemed inactive.

Terminal phase elimination half-life, single oral dose, fed-state = 22.5 hours

Bosutinib is a tyrosine kinase inhibitor. Although it is able to inhibit several tyrosine kinases such as Src, Lyn, and Hck, which are members of the Src-family of kinases, its primary target is the Bcr-Abl kinase. The Bcr-Abl gene is a chimeric oncogene created from the fusion of the breakpoint-cluster (Bcr) gene and Abelson (Abl) tyrosine gene. This chromosomal abnormality results in the formation of what is commonly known as the Philadelphia chromosome or Philadelphia translocation. The Bcr-Abl gene expresses a particular kinase that promotes the progression of CML. A decrease in the growth and size of the CML tumour has been observed following administration of bosutinib. Bosutinib did not inhibit the T315I and V299L mutant cells.

bosutinib

Human drugs -> Bosulif -> EMA Drug Category|Protein kinase inhibitors, Antineoplastic agents -> Human pharmacotherapeutic group|Human drugs -> Rare disease (orphan)|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients