Azacitidine

What it is and how it works

Mechanism of Action Azacitidine is a pyrimidine nucleoside analog of cytidine. Azacitidine is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of azacitidine required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis. Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. The cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms.

Mechanism class: Nucleic Acid Synthesis Inhibitors

Indications

Azacitidine for injection is a nucleoside metabolic inhibitor indicated for the treatment of: Adult patients with the following FAB myelodysplastic syndrome (MDS) subtypes: 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), and chronic myelomonocytic leukemia (CMMoL). Myelodysplastic Syndromes (MDS) Azacitidine for injection is indicated for treatment of adult patients with the following French-American-British (FAB) myelodysplastic syndrome subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL). Pediatric use information is approved for Celgene Corporation's Vidaza (azacitidine for injection).

Dosage and administration (summary)

Do not substitute Azacitidine for injection for oral azacitidine. The indications and dosing regimen for Azacitidine for injection differ from that of oral azacitidine ( 2.1 , 5.1 ). MDS: The recommended starting dosage for the first treatment cycle, for all patients regardless of baseline hematology values, is Azacitidine for injection 75 mg/m 2 daily for 7 days to be administered by subcutaneous injection or intravenous infusion. See full prescribing information for schedule for subsequent cycles. Premedicate for nausea and vomiting . Continue treatment as long as the patient continues to benefit . Monitor all patients for hematologic response and for renal toxicity.

Contraindications

Advanced Malignant Hepatic Tumors . Hypersensitivity to Azacitidine or Mannitol . Advanced Malignant Hepatic Tumors Azacitidine is contraindicated in patients with advanced malignant hepatic tumors [ see Warnings and Precautions ]. Hypersensitivity to Azacitidine or Mannitol Azacitidine is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol.

Warnings and precautions

Risks of Substitution with Other Azacitidine Products : Do not substitute Azacitidine for oral azacitidine ( 2.1 , 5.1 ). Anemia, Neutropenia and Thrombocytopenia : Monitor complete blood counts (CBC) frequently . Hepatotoxicity : Patients with severe preexisting hepatic impairment are at higher risk for toxicity . Renal Toxicity : Monitor patients with renal impairment for toxicity since azacitidine and its metabolites are primarily excreted by the kidneys . Tumor Lysis Syndrome : Azacitidine may cause fatal or serious tumor lysis syndrome, including in patients with MDS.

Pregnancy

Pregnancy Risk Summary Based on its mechanism of action and findings in animals, Azacitidine can cause fetal harm when administered to a pregnant woman [ see Clinical Pharmacology ]. There are no data on the use of azacitidine in pregnant women.

Storage and supply

How Supplied Azacitidine for injection is supplied as a lyophilized powder in 100 mg single-dose vials packaged in cartons of 1 vial (NDC 83774-102-01). Storage Store unreconstituted vials at 25º C (77º F); excursions permitted to 15º-30º C (59º-86º F) (See USP Controlled Room Temperature).

Source: Azacitidine For (Azacitidine) — US FDA prescribing information, 2024-12-16, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.