Imatinib (imatinib mesylate)

Imatinib mesylate, an inhibitor of Bcr-Abl tyrosine kinase, is an antineoplastic agent.

Imatinib mesylate, an inhibitor of Bcr-Abl tyrosine kinase, is an antineoplastic agent.

The Philadelphia chromosome, characteristic of chronic myelogenous leukemia (CML), is created by a reciprocal translocation between chromosomes 9 and 22. Translocation between these chromosomes results in production of an abnormal protein (Bcr-Abl tyrosine kinase) that exhibits enhanced tyrosine kinase activity (i.e., increased phosphorylation of tyrosine residues); phosphorylation of tyrosine residues on growth factor receptors is thought to be important in stimulating cell proliferation and inhibiting cell death (apoptosis). Imatinib competitively inhibits Bcr-Abl tyrosine kinase, thereby inhibiting tyrosine phosphorylation of proteins involved in Bcr-Abl signal transduction.

The drug has been shown to inhibit proliferation and induce apoptosis of Bcr-Abl-positive cells as well as fresh leukemic cells from Ph+ CML.

Imatinib also inhibits receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, and PDGF-mediated and SCF-mediated cellular events. Data from in vitro studies shows that imatinib inhibits proliferation and induces apoptosis in gastrointestinal stromal tumor (GIST) cells, which express an activating c-kit mutation.

Imatinib is well absorbed after oral administration with a maximum serum concentration achieved within 2 to 4 hours after a dose. Imatinib is approximately 95% bound to plasma protein and has an elimination half-life of approximately 18 hours. Administration of 260 mg/m2 or 340 mg/m2 in pediatric patients achieved an AUC similar to that attained with a 400 mg dose in adults.

Mean imatinib AUC increased proportionally with dose in adults but not in pediatric patients.

Imatinib is metabolized by the cytochrome P-450 (CYP) microsomal enzyme system, principally by the isoenzyme 3A4 (CYP3A4) and, to a lesser extent, by CYP1A2, CYP2D6, CYP2C9, and CYP2C19. The active metabolite, an N-demethylated piperazine derivative, formed principally by CYP3A4, accounts for approximately 15% of total plasma concentrations of the drug. Approximately 68 and 13% of an oral dose of imatinib is excreted in feces and urine, respectively, as active and inactive metabolites within 7 days.

Apparent oral clearance appears to be similar in adults and pediatric patients.

USES: This medication is used to treat certain types of cancer (such as acute lymphoblastic leukemia, chronic myeloid leukemia, gastrointestinal stromal tumors, and myelodysplastic/myeloproliferative diseases). It works by slowing or stopping the growth of cancer cells. Imatinib may also be used to treat certain immune system disorders (such as aggressive systemic mastocytosis, hypereosinophilic syndrome).

Generic name: imatinib mesylate
Pronunciation: (im-A-ti-nib)

The following indications are listed for Imatinib:

• Accelerated Phase Philadelphia Chromosome Positive Chronic Myelocytic Leukemia
• Adjuvant Therapy Following Surgical Resection Of Kit (Cd117) Positive Gastrointestinal Stromal Tumor
• Aggressive Systemic Mastocytosis
• Chronic Eosinophilic Leukemia
• Chronic Phase Philadelphia Chromosome Positive Chronic Myelocytic Leukemia
• Dermatofibrosarcoma Protuberans
• Hypereosinophilic Syndrome
• Lymphoid Blast Phase Philadelphia Chromosome Positive Chronic Myelocytic Leukemia
• Myelodysplastic, Myeloproliferative Diseases Associated With Platelet-Derived Growth Factor Receptor
• Myeloid Blast Phase Philadelphia Chromosome Positive Chronic Myelocytic Leukemia
• Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
• Unresectable Or Metastatic Kit (Cd117) Positive Gastrointestinal Stromal Tumor

Also known as: Accelerated Phase Ph(+) Cml, Accelerated Phase Ph1(+) Cml, Accelerated Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia, Accelerated Phase, Bcr/Abl Positive Cml, Acute Lymphoblastic Leukemia, T(9;22)(Q34;Q11), Adjuvant Therapy Following Surgical Resection Of Kit (Cd117) Positive Gist, Adjuvant Therapy Of Kit+ Gastrointest Stromal Tumor, Bcr/Abl Positive Acute Lymphoblastic Leukemia, Bcr/Abl Positive Cml In Lymphoid Blast Crisis, Bcr/Abl Positive Cml In Myeloid Blast Crisis, Chronic Phase Ph(+) Cml, Chronic Phase Ph1(+) Cml, Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia, Chronic Phase, Bcr/Abl Positive Cml, Lymphoid Blast Phase Ph(+) Cml, Lymphoid Blast Phase Ph1(+) Cml, Lymphoid Blast Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia, Mds And Mpd Associated With Pdgfr Genetic Arrangements, Myeloid Blast Phase Ph(+) Cml, Myeloid Blast Phase Ph1(+) Cml, Myeloid Blast Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia, Ph(+) Cml, Accelerated Phase, Ph(+) Cml, Chronic Phase, Ph(+) Cml, Lymphoid Blast Phase, Ph(+) Cml, Myeloid Blast Phase, Ph1(+) Cml, Accelerated Phase, Ph1(+) Cml, Chronic Phase, Ph1(+) Cml, Lymphoid Blast Phase, Ph1(+) Cml, Myeloid Blast Phase, Philadelphia Chromosome (+) Cml In Myeloid Blast Crisis, Philadelphia Chromosome Positive Chronic Myelocytic Leukemia In Lymphoid Blast Crisis, Unresectable Or Metastatic Cd117+ Gist, Unresectable Or Metastatic Kit+ Gist.

No ICD codes are available for this drug.