Azacitidine is a pyrimidine nucleoside analogue and a hypomethylating agent used primarily in the treatment of myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). It is a cytotoxic and epigenetic modifier that incorporates into DNA and RNA, leading to cell death and reversal of aberrant DNA hypermethylation. In India, it is a critical, high-cost therapy for hematological malignancies, often requiring specialist management and patient assistance programs.
Adult: 75 mg/m² body surface area (BSA) administered subcutaneously or intravenously daily for 7 days, every 28 days. The 100mg vial is used to prepare the dose based on BSA calculation. Dose may be increased to 100 mg/m² if no beneficial effect is seen after 2 cycles and no toxicity other than nausea/vomiting.
Note: Reconstitute the 100mg vial with 4 mL of Sterile Water for Injection to get a concentration of 25 mg/mL. For SC administration, further dilute with 0.9% Sodium Chloride Injection if needed. Administer SC injections by rotating sites (thigh, abdomen, upper arm). IV administration is given as a 10-40 minute infusion. Pre-medicate with antiemetics (e.g., 5-HT3 antagonist).
Azacitidine exerts dual mechanisms: 1) Cytotoxicity: It is incorporated into DNA and RNA, disrupting nucleic acid metabolism and inhibiting protein synthesis, leading to apoptosis of rapidly dividing cells, especially in the bone marrow. 2) Hypomethylation: It is a potent inhibitor of DNA methyltransferase. By incorporating into DNA and covalently binding to methyltransferases, it causes irreversible inactivation, leading to DNA hypomethylation. This reverses the silencing of tumor suppressor genes and promotes normal differentiation and maturation of hematopoietic cells in MDS.
Pregnancy: Category D. Azacitidine is teratogenic and embryotoxic in animal studies. It can cause fetal harm. Women of childbearing potential must use effective contraception during and for at least 6 months after therapy. Men should use contraception during and for 3 months after therapy.
Driving: May cause fatigue, dizziness, and weakness. Patients should be cautioned about operating machinery or driving if they experience these effects.
| Live Vaccines (e.g., MMR, Varicella, Yellow Fever) | Risk of severe or fatal infection due to immunosuppression. | Major |
| Nephrotoxic drugs (e.g., Aminoglycosides, NSAIDs, IV Contrast) | Increased risk of renal toxicity. | Moderate |
| Other Myelosuppressive agents (e.g., Chemotherapy, Clozapine) | Additive myelosuppression, increasing risk of infection and bleeding. | Major |
| Warfarin | Potential increased risk of bleeding due to thrombocytopenia; monitor INR closely. | Moderate |