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Dasatinib

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Clinical use of Dasatinib

Dasatinib is a selective tyrosine kinase receptor inhibitor that is used in the therapy of chronic myelogenous leukemia (CML) positive for the Philadelphia chromosome.   

Liver safety of Dasatinib

Dasatinib is commonly associated with transient elevations in serum aminotransferase levels during treatment, but with only rare instances of clinically apparent acute liver injury

Mechanism of action of Dasatinib

Dasatinib is an orally available, small molecule 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 underlies the Philadelphia chromosome of chronic myelogenous leukemia (CML).  The abnormal tyrosine kinase receptor is constitutively expressed and causes abnormal cell growth and proliferation.  Inhibition of the enzyme can lead to dramatic reversal of progression of leukemia and is highly effective, although limited by the development of tumor resistance caused by mutations in the kinase.  Dasatinib is actually a multi-kinase inhibitor and also has activity against scr, c-Kit and ephrin receptors, among others. 

FDA approval information for Dasatinib

Dasatanib received approval for use in the United States in 2006 and is one of five such specific inhibitors of BCR-ABL approved for clinical use, the others being imatinib [2001], nilotinib [2007], bosutinib [2012] and ponatinib [2012]. 

Dosage and administration for Dasatinib

Dasatinib is available in tablets of 20, 50, 70, 80, 100 and 140 mg under the brand name Sprycel.  Current indications are for treatment of Philadelphia chromosome-positive CML in the chronic, accelerated or blast phase usually after failure of a previous treatment.  It is also approved for use in adutls with Philadelphia chromcsome-positive acute lymphoblastic leukemia.  The typical dose is 100 to 140 mg daily. 

Side effects of Dasatinib

Common side effects include bone marrow suppression, fluid retention, diarrhea, headache, muscle cramps, arthralgias, fatigue, dyspnea, cough, pleural effusions and rash.  Rare, but potentially severe side effects include bone marrow suppression, QTc prolongation, heart failure and pulmonary artery hypertension.

 

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