Decitabine is used for the treatment of adult patients with myelodysplastic syndromes (MDS). This includes both previously treated and untreated cases, as well as de novo and secondary MDS across all French-American-British (FAB) subtypes: refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. It is also indicated for patients classified under the International Prognostic Scoring System (IPSS) as intermediate-1, intermediate-2, and high-risk groups.

Decitabine is thought to produce its anticancer effects after being phosphorylated and directly incorporated into DNA, where it inhibits DNA methyltransferase. This leads to DNA hypomethylation, which can trigger cellular differentiation or apoptosis. In vitro, decitabine blocks DNA methylation at concentrations that do not significantly suppress DNA synthesis. The hypomethylation induced by decitabine in cancer cells may help restore the normal function of genes responsible for regulating cell differentiation and proliferation. In rapidly dividing cells, its cytotoxic effect may also result from the formation of covalent bonds between DNA methyltransferase and decitabine that has been incorporated into DNA. In contrast, non-proliferating cells are relatively less sensitive to decitabine.

Three Day Regimen: Administer DACOGEN at a dose of 15 mg/m2 by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 days. Repeat cycles every 6 weeks upon hematologic recovery (ANC at least 1,000/µL and platelets at least 50,000/µL) for a minimum of 4 cycles. . A complete or partial response may take longer than 4 cycles. Delay and reduce dose for hematologic toxicity

Five Day Regimen: Administer DACOGEN at a dose of 20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days. Delay and reduce dose for hematologic toxicity (see Dose Modifications for Toxicity). Repeat cycles every 4 weeks upon hematologic recovery (ANC at least 1,000/µL and platelets at least 50,000/µL) for a minimum of 4 cycles. A complete or partial response may take longer than 4 cycles.

No formal drug interaction studies have been performed with decitabine. In vitro experiments using human liver microsomes indicate that decitabine is unlikely to inhibit or induce cytochrome P450 enzymes. Metabolism studies in vitro also show that decitabine is not a substrate for human hepatic cytochrome P450 enzymes. Since decitabine has minimal plasma protein binding (<1%), clinically significant interactions due to displacement of highly protein-bound drugs are not expected.

The most frequently reported adverse reactions (occurring in more than 50% of patients) include neutropenia, thrombocytopenia, anemia, and fever (pyrexia).

Based on available human data, animal studies, and its mechanism of action, decitabine may cause fetal harm when given during pregnancy. Breastfeeding is not recommended during treatment. There is no information available on whether decitabine or its metabolites are present in human breast milk, nor are there data regarding its effects on the breastfed infant or on milk production.

Neutropenia and thrombocytopenia: Monitor patients with complete blood counts and platelet counts regularly.
Embryo-fetal toxicity: Decitabine may cause harm to the fetus. Inform patients with reproductive potential about the possible risk to the fetus and advise them to use effective contraception during treatment.

Store at a temperature below 25°C, protected from light and moisture. Keep the medicine out of reach of children.