Azacitidine 5Azacytidine

5-Azacytidine and the closely related investigational drug decitabine (2'-dexoy-5-azacytidine) have antileukemic activity and induce differentiation. 5-Azacytidine is approved for treatment of myelodysplasia; it induces normalization of bone marrow in 15-20% of patients and reduces transfusion requirement in one-third of patients. It becomes incorporated into RNA and DNA and inhibits methylation of DNA, inducing the expression of silenced genes. Thus, it also is used to induce fetal hemoglobin (HbF) synthesis in sickle cell anemia, although it has been largely replaced for this indication by hydroxyurea. It undergoes very rapid deamination by cytidine deaminase, the product hydrolyzing to inactive metabolites. Its major toxicities include myelosuppression, and rather severe nausea and vomiting when given intravenously in large doses (150-200 mg/m2/day for 5 days). In low-dose daily subcutaneous regimens for myelodysplasia, 30 mg/m2/day, it is well tolerated.

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