Imatinib

An anticancer medication. Chronic intestinal disease that causes abdominal pain and diarrhea.

Information about Imatinib

  Imatinib is specific tyrosine kinase receptor inhibitor that is used in the therapy of Philadelphia chromosome-positive chronic myelogenous leukemia and gastrointestinal stromal tumors, both of which are marked by an abnormal, constitutively expressed tyrosine kinase that causes unregulated cell growth. 

Liver safety of Imatinib

Imatinib therapy is associated with transient elevations in serum aminotransferase levels and rare instances of clinically apparent acute liver injury which can be severe and sometimes fatal. 

Mechanism of action of Imatinib

Imatinib (im a' ti nib) is a specific inhibitor of the unique bcr-abl tyrosine kinase receptor, which is the product of a fusion gene resulting from the translocation between chromosomes 9 and 22 that characterizes the Philadelphia chromosome (Ph) of chronic myelogenous leukemia (CML).  The abnormal tyrosine kinase receptor is constitutively expressed and causes abnormal cell growth and proliferation.  Introduction of imatinib into clinical medicine was an important advance in the therapy of cancer, the first antineoplastic agent specially directed at a molecular abnormality that occurs in cancer cells.  Inhibition of the enzyme can lead to dramatic reversal of progression of Ph+ leukemia and is highly effective, although limited by the development of tumor resistance caused by mutations in the kinase.  A similar abnormal tyrosine kinase (cKit) is also found in gastrointestinal stromal tumors (GIST). 

FDA approval information for Imatinib

Imatinib received accelerated approval for use in the United States in May 2001 and subsequent full approval in December 2005.  Imatinib is available in tablets of 100 and 400 mg generically and under the brand name Gleevec. 

Clinical use of Imatinib

Current indications are for Philadelphia chromosome positive (Ph+) CML and Ph+ acute lymphoblastic leukemia, for unresectable or metastatic GIST with positive Kit (CD117) and for other malignant syndromes with other kinase mutations sensitive to imatinib including myelodysplastic disorders and systemic mastocytosis. 

Dosage and administration for Imatinib

The typical dose is 400 to 600 mg once daily. 

Side effects of Imatinib

Side effects include nausea, edema, muscle cramps, arthralgias, fatigue, fever, headache, abdominal discomfort, diarrhea, anemia, cough, rash and pruritus.  Rare, but potentially severe adverse events include severe myelosuppression, congestive heart failure, cardiogenic shock, hemorrhage, severe rash, embryo-fetal toxicity, tumor lysis syndrome, renal toxicity and growth retardation.

 

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