Brands, Medical Use, Clinical Data
- Antimetabolites, Antineoplastic
- Enzyme Inhibitors
- Azacitidine for injectable suspension is supplied as a lyophilized powder in 100 mg single-use vials packaged in cartons of 1 vial.
Brands / Synonyms
5 AZC; Azacitidina [INN-Spanish]; Azacitidine [USAN:INN]; Azacitidinum [INN-Latin]; Azacytidine; Ladakamycin; Mylosar; Vidaza
For treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia.
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. Non-proliferating cells are relatively insensitive to azacitidine.
Mechanism of Action
Azacitidine (5-azacytidine) causes hypomethylation of DNA and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow, resulting in cell death. 5-azacytidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Cells in the presence of 5-azacytidine incorporate it into DNA during transcription and RNA during translation. The incorporation of 5-azacytidine into DNA or RNA inhibits methyltransferase thereby causing demethylation in that sequence, affecting the way that cell regulation proteins are able to bind to the DNA/RNA substrate.
Azacitidine is rapidly absorbed after subcutaneous administration. The bioavailability of subcutaneous azacitidine relative to IV azacitidine is approximately 89%, based on area under the curve.
One case of overdose with azacitidine was reported during clinical trials. A patient experienced diarrhea, nausea, and vomiting after receiving a single IV dose of approximately 290 mg/m2, almost 4 times the recommended starting dose.
Biotrnasformation / Drug Metabolism
An in vitro study of azacitidine incubation in human liver fractions indicated that azacitidine may be metabolized by the liver. The potential of azacitidine to inhibit cytochrome P450 (CYP) enzymes is not known.
Vidaza is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol. Vidaza
is also contraindicated in patients with advanced malignant hepatic tumors.
No formal assessments of drug-drug interactions between Vidaza and other agents have been