Decitabine — Drug Monograph

Brand names: Dacogen, Inqovi

Drug class: Antimetabolite

Mechanism of Action

Decitabine (5-aza-2'-deoxycytidine) is a deoxycytidine analog hypomethylating agent that, after phosphorylation to its active triphosphate form, is incorporated directly into DNA (unlike azacitidine which is also incorporated into RNA). Once incorporated, it forms irreversible covalent complexes with DNA methyltransferases (DNMT1, DNMT3a, DNMT3b), leading to their degradation and progressive global DNA demethylation with each cell division. This hypomethylation reactivates epigenetically silenced tumor suppressor genes, restores differentiation pathways, and promotes apoptosis. Decitabine is…

FDA Indications

• Myelodysplastic syndromes (MDS) — intermediate- and high-risk subtypes (Dacogen IV; FDA approved 2006, DACO-007/ADOPT trials)
• Acute myeloid leukemia (AML) — decitabine 35 mg/m² + cedazuridine 100 mg oral fixed-dose combination (Inqovi; FDA approved 2020, ASTX727-02 trial demonstrating pharmacokinetic equivalence to IV decitabine)

Common Side Effects

• Myelosuppression (neutropenia, thrombocytopenia, anemia) — very common
• Fatigue
• Nausea
• Constipation
• Diarrhea
• Fever
• Peripheral edema
• Hyperglycemia
• Cough
• Rash and skin changes

Clinical Pearl

Inqovi (decitabine/cedazuridine) represents a major advance in HMA therapy by enabling fully oral administration with IV-equivalent pharmacokinetics, as cedazuridine blocks cytidine deaminase in the GI tract and liver that would otherwise rapidly degrade oral decitabine. The 5-day-every-28-days IV schedule of decitabine is preferred over the 3-day q8h schedule due to comparable efficacy with significantly improved tolerability and outpatient feasibility. Like azacitidine, response assessment…

Related Therapies & Mechanisms

• Azacitidine (Vidaza) — Antimetabolite · Leukemia
• Cladribine (Leustatin) — Antimetabolite · Leukemia
• Clofarabine (Clolar) — Antimetabolite · Leukemia
• Cytarabine (Cytosar-U) — Antimetabolite · Leukemia