Decitabine an Cedazuridine

Inqovi tradename.



A combination of decitabine, a nucleoside metabolic inhibitor, and cedazuridine, a cytidine deaminase inhibitor is indicated for the treatment of adult patients with myelodysplastic syndromes (MDS).



MDS includes  previously treated and untreated, de novo and secondary MDS with the following French-AmericanBritish subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.



It is a tablet for oral administration.



1 tablet (35 mg decitabine and 100 mg cedazuridine) taken orally once daily on Days 1 through 5 of each 28-day cycle. 



Tablets are not cut, crush, or chewed.



Two randomized, open-label crossover trials: The ASTX727-01-B trial included 80 adults with myelodysplastic syndrome (IPPS intermediate-1, intermediate-2 or high risk) or CMML. The ASTX727-02 trial included 133 adults with myelodysplastic syndrome or CMML, including those with all French-American-British classification criteria and IPSS prognostic scores. 



Approximately half of the patients who had been dependent on transfusions no longer required red blood cell or platelet transfusions during any consecutive 8-week post-baseline period.



Side Effects: 



































febrile neutropenia












decreased appetite



upper respiratory tract infection






transaminase increased



Grade 3 or 4  abnormalities (≥ 50%): leukocytes decreased, platelet count decreased, neutrophil count decreased, and hemoglobin decreased



Decitabine is a nucleoside metabolic inhibitor that exerts its effects after phosphorylation and direct incorporation into DNA and inhibition of DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation and/or apoptosis. 



Decitabine inhibits DNA methylation, may restore normal function to genes that are critical for the control of cellular differentiation and proliferation of cancer cells.



Decitabine cytotoxicity  may also be attributed to the formation of covalent adducts between DNA methyltransferase and decitabine incorporated into DNA. 



Non-proliferating cells are relatively insensitive to decitabine.



Cytidine deaminase (CDA) enzyme catalyzes the degradation of cytidine, including the cytidine analog decitabine. 



High levels of CDA in the gastrointestinal tract and liver degrade decitabine and limit its oral bioavailability. 



Cedazuridine is a cytidine deaminase inhibitor that increases systemic exposure of decitabine.



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