How it is administered

Azacitidine is given as an injection, either under the skin (subcutaneous) or directly into a vein (intravenous infusion). It comes as a sterile powder in vials that are reconstituted before use. The usual starting dose for adults is 75 mg/m² once daily for 7 days, repeated every 4 weeks. The medication can be given in a hospital or clinic setting by a healthcare professional. The injection sites (thigh, abdomen, or upper arm) are rotated to minimize irritation. The intravenous infusion is administered over 10 to 40 minutes.

How it works

Azacitidine is a type of chemotherapy known as a nucleoside metabolic inhibitor. It is a pyrimidine nucleoside analog of cytidine. Azacitidine works by two main mechanisms:

1. Hypomethylation of DNA: In certain blood cancers, such as myelodysplastic syndromes (MDS), abnormal cells have changes in their DNA that silence important genes. Azacitidine can reverse this process by reducing the methylation (a chemical modification) of DNA. This can help restore the normal function of genes that control cell growth and differentiation.

2. Direct cytotoxicity: Azacitidine is toxic to abnormal blood-forming cells in the bone marrow. It kills rapidly dividing cells, including cancer cells that are not responding to normal growth controls. Non-dividing (resting) cells are less affected by azacitidine.

By these actions, azacitidine helps reduce the number of abnormal cells and allows healthy blood cells to grow.

Who Should take it

Azacitidine is used to treat adults with certain types of myelodysplastic syndromes (MDS), which are a group of blood cancers that affect how bone marrow produces blood cells. Specifically, it is indicated for:

• Refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) (if accompanied by neutropenia or thrombocytopenia or requiring transfusions)
• Refractory anemia with excess blasts (RAEB)
• Refractory anemia with excess blasts in transformation (RAEB-T)
• Chronic myelomonocytic leukemia (CMMoL)

These conditions are characterized by abnormal, poorly functioning blood cells and an increased risk of progression to acute myeloid leukemia (AML). Azacitidine can help improve blood counts, reduce transfusion needs, and may prolong survival in these patients.

Who should not take it

Azacitidine should not be used in:

• Patients with advanced malignant hepatic (liver) tumors, as it may worsen liver function and can be dangerous in these cases.
• Patients with a known hypersensitivity or allergy to azacitidine or mannitol (an ingredient in the formulation).

Caution is needed in patients with severe pre-existing liver or kidney impairment, as they may be at higher risk for toxicity. Azacitidine is not recommended for use in pregnant women due to the risk of harm to the unborn baby. Women of childbearing potential and men with partners of childbearing potential should use effective contraception during treatment.

Commonly used with

Azacitidine is often used as a single agent for the treatment of myelodysplastic syndromes. Supportive care measures, such as blood transfusions, antibiotics, antiemetics (for nausea), and growth factors, may be used alongside azacitidine to manage symptoms and side effects. It is not typically combined with other chemotherapy drugs for MDS, but may be used with other supportive medications as needed.

Commonly tested with

In clinical studies, azacitidine has been compared to best supportive care, low-dose cytarabine, and intensive chemotherapy regimens in patients with MDS. It is also sometimes studied in combination with other agents in clinical trials, but for FDA-approved use in MDS, it is generally used alone with supportive care.