Mechanism of action of imatinib mesylate is:
lmatinib :This novel antineoplastic drug inhibits the tyrosine protein kinases in chronic myeloid leukaemia (CML) cells and the ones that are activated by platelet derived growth factor (PDGF) receptor, stem cell receptor and c-kit receptor found in gastrointestinal stromal tumour (GIST), a rare tumour. Stricking success has been obtained in chronic phase of CML as well as in accelerated phase, and in metastatic kit-positive GIST. Adverse effects are fluid retention, edema, vomiting, abdominal pain, myalgia and liver damage. Mechanism of Action: Protein-tyrosine kinase inhibitor, specific for abnormal BCR-ABL tyrosine kinase produced by Philadelphia chromosome in CML/ALL USES: Acute Lymphoblastic Leukemia Indicated for adults with relapsed or refractory Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) 600 mg PO qDay Myelodysplastic/Myeloproliferative Diseases Indicated in adults with myelodysplastic/ myeloproliferative diseases associated with platelet-derived growth factor receptor gene re-arrangements as determined with an FDA-approved test 400 mg PO qDay Hypereosinophilic Syndrome/Eosinophilic Leukemia Indicated for adults with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFR-alpha fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFR-alpha fusion kinase negative or unknown 400 mg PO qDay In patients with demonstrated F1P1L1-PDGFR-alpha fusion kinase: 100 mg PO qDay; may increase to 400 mg qDay in the absence of adverse drug reactions if assessments demonstrate an insufficient response to therapy Chronic Myeloid Leukemia Chronic phase Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase 400 mg PO qDay Chronic phase after failure of interferon-alpha therapy: May increase to 600 mg/day in the absence of severe adverse drug reaction and severe nonleukemia related neutropenia or thrombocytopenia in the following circumstances: disease progression (at any time), failure to achieve a satisfactory hematologic response after at least 3 months of treatment, failure to achieve a cytogenetic response after 6-12 months of treatment, or loss of a previously achieved hematologic or cytogenetic response Accelerated phase or blast crisis 600 mg PO qDay May increase to 400 mg PO q12hr in the absence of severe adverse drug reaction and severe nonleukemia related neutropenia or thrombocytopenia in the following circumstances: disease progression (at any time), failure to achieve a satisfactory hematologic response after at least 3 months of treatment, failure to achieve a cytogenetic response after 6-12 months of treatment, or loss of a previously achieved hematologic or cytogenetic response Dermatofibrosarcoma Protuberans Indicated for adults with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans 400 mg PO q12hr Mastocytosis Indicated for adults with aggressive systemic mastocytosis without the D816V c-Kit mutation as determined with an FDA-approved test or with c-Kit mutational status unknown Without D816V c-Kit mutation: 100 mg PO qDay c-Kit mutational status unknown: 400 mg PO qDay if not responding to other therapies ASM associated with eosinophilia (a clonal hematological disease related to the fusion kinase FIP1L1-PDGFR-alpha): 100 mg PO qDay initially, may increase to 400 mg/day in absence of adverse effects if response to therapy is insufficient Gastrointestinal Stromal Tumors Unresectable and/or metastatic malignant GIST 400 mg PO qDay; may increase to 400 mg BID in patients showing clear signs or symptoms of disease progression at a lower dose and in the absence of severe adverse drug reactions REFERENCE:ESSENTIALS OF MEDICAL PHARMACOLOGY, www.medscape.com K.D.TRIPATHI SIXTH EDITION PAGE NO:828
Inscrease in metabolism of P glycoprotein
Blocking the action of P glycoprotein
Blocks the action of chimeric fusion protein of bcrabl
Non-competitive inhibition of ATP binding site
Chemotherapy