5azacytidine

5-azacytidine, also known as azacitidine, is a cytidine analogue used as a chemotherapy and epigenetic therapy. It is approved for certain myelodysplastic syndromes and for adult patients with acute myeloid leukemia who are not candidates for more intensive treatment. It is a nucleoside analogue in which a nitrogen replaces carbon at position 5 of the pyrimidine ring, enabling its unique biological effects.

Mechanism of action is dual. The compound is incorporated into RNA in place of cytidine, which can disrupt RNA processing and protein synthesis. It is also phosphorylated to its triphosphate forms and incorporated into DNA after conversion to a deoxynucleotide form; most of its therapeutic effect comes from inhibition of DNA methyltransferases. By trapping DNMT enzymes and reducing DNA methylation, 5-azacytidine can reactivate silenced genes and promote differentiation or apoptosis of malignant cells, contributing to its disease-modifying activity in myelodysplastic syndromes and certain leukemias.

Clinical use covers myelodysplastic syndromes, including subtypes with higher risk, and some forms of AML in patients unsuitable for intensive chemotherapy. It may be used alone or in combination with other agents, depending on disease characteristics and guidelines.

Administration is typically by subcutaneous injection or intravenous infusion in cycles. A common regimen in adults is 75 mg/m2 administered daily for 7 consecutive days every 28 days, though dosing can vary by protocol and indication.

Adverse effects are primarily hematologic and may include cytopenias, infection, fatigue, and nausea. Other effects can include injection-site reactions, mucositis, and diarrhea. The drug is contraindicated in certain pregnancy situations.