Dacogen - General Information
Dacogen is indicated for treatment of patients with myelodysplastic syndrome (MDS). It is a chemical analogue of cytidine, a nucleoside present in DNA and RNA. Cells in the presence of Dacogen incorporate it into DNA during replication and RNA during transcription. The incorporation of Dacogen into DNA or RNA inhibits methyltransferase thereby causing demethylation in that sequence. This adversely affects the way that cell regulatory proteins are able to bind to the DNA/RNA substrate.
Pharmacology of Dacogen
Dacogen is an analogue of the natural nucleoside 2’-deoxycytidine. It functions in the same way as 5-Azacytidine.
Dacogen for patients
Patients should inform their physician about any underlying liver or kidney disease.
Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Dacogen.
Men should be advised not to father a child while receiving treatment with Dacogen, and for 2 months afterwards.
Drug interaction studies with decitabine have not been conducted. In vitro studies in human liver microsomes suggest that decitabine is unlikely to inhibit or induce cytochrome P450 enzymes. In vitro metabolism studies have suggested that decitabine is not a substrate for the human liver cytochrome P450 enzymes. As plasma protein binding of decitabine is negligible (<1%), interactions due to displacement of more highly protein bound drugs from plasma proteins are not expected.
Dacogen is contraindicated in patients with a known hypersensitivity to decitabine.
Additional information about Dacogen
Dacogen Indication: For treatment of patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.
Mechanism Of Action: Dacogen is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into DNA and inhibition of DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation or apoptosis. Dacogen inhibits DNA methylation in vitro, which is achieved at concentrations that do not cause major suppression of DNA synthesis. Dacogen-induced hypomethylation in neoplastic cells may restore normal function to genes that are critical for the control of cellular differentiation and proliferation. In rapidly dividing cells, the cytotoxicity of decitabine 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.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Decitabine
Synonyms: Azadc; DAC; Dezocitidine; 5-aza-2'-deoxycytidine
Drug Category: Antineoplastic Agents; Antimetabolites, Antineoplastic; Enzyme Inhibitors; Teratogens
Drug Type: Small Molecule; Approved; Investigational
Absorption: Not Available
Toxicity (Overdose): There is no known antidote for overdosage with decitabine. Higher doses are associated with increased myelosuppression including prolonged neutropenia and thrombocytopenia.
Protein Binding: Plasma protein binding of decitabine is negligible (<1%).
Biotransformation: The exact route of elimination and metabolic fate of decitabine is not known in humans. One of the pathways of elimination of decitabine appears to be deamination by cytidine deaminase found principally in the liver but also in granulocytes, intestinal epithelium and whole blood.
Half Life: The terminal phase elimination half-life is 0.51 ± 0.31 hours.
Dosage Forms of Dacogen: Powder, for solution Intravenous
Chemical IUPAC Name: 4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin-2-one
Chemical Formula: C8H12N4O4
Decitabine on Wikipedia: https://en.wikipedia.org/wiki/Decitabine
Organisms Affected: Humans and other mammals