Azacitidine — Drug Monograph
Brand names: Vidaza, Onureg
Drug class: Antimetabolite
Mechanism of Action
Azacitidine is a pyrimidine nucleoside analog of cytidine and a hypomethylating agent (HMA). After cellular uptake and phosphorylation, it is incorporated into DNA and RNA strands where it traps DNA methyltransferases (DNMT1, DNMT3a, DNMT3b) in covalent complexes, causing their proteasomal degradation. This leads to global DNA hypomethylation, re-expression of silenced tumor suppressor genes (including p15/CDKN2B, p16/CDKN2A), and restoration of normal differentiation programs. At higher doses, direct cytotoxic effects from RNA and DNA strand incorporation also contribute.
FDA Indications
- Myelodysplastic syndromes (MDS) — all FAB subtypes including refractory anemia, RAEB, RAEB-T, and CMML (Vidaza SC/IV; FDA approved 2004, pivotal Cancer and Leukemia Group B CALGB 9221 trial)
- Acute myeloid leukemia (AML) — maintenance therapy following induction chemotherapy in patients not eligible for HSCT (Onureg oral; FDA approved 2020, QUAZAR AML-001 trial: improved OS median 24.7 vs. 14.8 months)
Common Side Effects
- Myelosuppression (neutropenia, thrombocytopenia, anemia)
- Nausea and vomiting
- Injection site reactions (erythema, bruising, tenderness — SC)
- Constipation or diarrhea
- Fatigue
- Fever
- Peripheral edema
- Ecchymosis
- Cough and dyspnea
- Anorexia
Clinical Pearl
Azacitidine requires a minimum of 4–6 cycles before declaring treatment failure, as responses are often delayed and the mechanism (epigenetic reprogramming) requires multiple cycles for gene re-expression. Approximately 17% of patients who initially achieve only stable disease will eventually convert to a complete or partial remission with continued therapy. The VIALE-A trial established azacitidine plus venetoclax as a new standard of care for AML patients ineligible for intensive…
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