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Pronunciationay" za sye' ti deen
Trade namesVidaza, Azadine, Onureg
Other names5-Azacytidine, azacytidine, ladakamycin, 4-Amino-1-β-D-ribofuranosyl-s-triazin-2(1H)-one, U-18496, CC-486
  • 4-Amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one
Clinical data
Drug classNucleoside analog[1]
Main usesMyelodysplastic syndrome, acute myeloid leukaemia (AML), chronic myelomonocytic leukaemia[2][3]
Side effectsNausea, low red blood cells, low platelets, fever, low white blood cells, diarrhea, low potassium, bruises[4]
  • AU: X (High risk)[5]
Routes of
Subcutaneous injection, intravenous, by mouth
External links
License data
Legal status
Elimination half-life4 hr.[8]
Chemical and physical data
Molar mass244.207 g·mol−1
3D model (JSmol)
  • O=C1/N=C(\N=C/N1[C@@H]2O[C@@H]([C@@H](O)[C@H]2O)CO)N
  • InChI=1S/C8H12N4O5/c9-7-10-2-12(8(16)11-7)6-5(15)4(14)3(1-13)17-6/h2-6,13-15H,1H2,(H2,9,11,16)/t3-,4-,5-,6-/m1/s1 checkY

Azacitidine, sold under the brand name Vidaza among others, is a medication used to treat myelodysplastic syndrome, acute myeloid leukaemia (AML), chronic myelomonocytic leukaemia.[2][3] It is given by injection into a vein or under the skin.[1]

Common side effects include nausea, low red blood cells, low platelets, fever, low white blood cells, diarrhea, low potassium, and bruises.[4] Other side effects may include liver problems, kidney problems, and tumor lysis syndrome.[4] Use in pregnancy may harm the baby.[4] It is a cytosine analogue which works by blocking DNA methylation.[2]

Azacitidine was approved for medical use in the United States in 2004 and Europe in 2008.[4][9] It is available as a generic medication.[3] In the United Kingdom 100 mg costs the NHS about £220 as of 2021.[3] In the United States this amount costs about 83 USD.[10]

Medical uses

Azacitidine is used mainly in the treatment of myelodysplastic syndrome, for which it received approval by the U.S. Food and Drug Administration (FDA) on May 19, 2004.[11][7][12] In two randomized controlled trials comparing azacitidine to supportive treatment, 16% of subjects with myelodysplastic syndrome who were randomized to receive azacitidine had a complete or partial normalization of blood cell counts and bone marrow morphology, compared to none who received supportive care, and about two-thirds of patients who required blood transfusions no longer needed them after receiving azacitidine.[13]

It is also sometimes used for the treatment of acute myeloid leukemia,[14] as a hypomethylating agent; an oral version called CC-486 is being tested as an easier to administer treatment for AML.[15]

Side effects

Azacitidine causes anemia (low red blood cell counts), neutropenia (low white blood cell counts), and thrombocytopenia (low platelet counts), and patients should have frequent monitoring of their complete blood counts, at least prior to each dosing cycle. The dose may have to be adjusted based on nadir counts and hematologic response.[7]

It can also be hepatotoxic in patients with severe liver impairment, and patients with extensive liver tumors due to metastatic disease have developed progressive hepatic coma and death during azacitidine treatment, especially when their albumin levels are less than 30 g/L. It is contraindicated in patients with advanced malignant hepatic tumors.[7]

Kidney toxicity, ranging from elevated serum creatinine to kidney failure and death, have been reported in patients treated with intravenous azacitidine in combination with other chemotherapeutic agents for conditions other than myelodysplastic syndrome. Renal tubular acidosis developed in five patients with chronic myelogenous leukemia (an unapproved use) treated with azacitidine and etoposide, and patients with renal impairment may be at increased risk for renal toxicity. Azacitidine and its metabolites are primarily excreted by the kidneys, so patients with chronic kidney disease should be closely monitored for other side effects, since their levels of azacitidine may progressively increase.[7]

Based on animal studies and its mechanism of action, azacitidine can cause severe fetal damage. Sexually active women of reproductive potential should use contraception during while receiving azacitidine and for one week after the last dose, and sexually active men with female partners of reproductive potential should use contraception during treatment and for three months following the last dose.[7]

A study undertaken to evaluate the immediate and long-term effects of a single-day exposure to Azacytidine (5-AzaC) on neurobehavioral abnormalities in mice found, that the inhibition of DNA methylation by 5-AzaC treatment causes neurodegeneration and impairs extracellular signal-regulated kinase (ERK1/2) activation and the activity-regulated cytoskeleton-associated (Arc) protein expression in neonatal mice and induces behavioral abnormalities in adult mice, as DNA methylation-mediated mechanisms appear to be necessary for the proper maturation of synaptic circuits during development, and disruption of this process by 5-AzaC could lead to abnormal cognitive function.[16]

Azacitidine can also cause nausea, vomiting, fevers, diarrhea, redness at its injection sites, constipation, bruising, petechiae, rigors, weakness, abnormally low potassium levels in the bloodstream, and many other side effects, some of which can be severe or even fatal.[7]

Mechanism of action

Images of myeloma cells a) untreated cells b) 100 μM azacytidine-treated cells for 24 h c) H2O2-treated cells d-e) detection of ROS in untreated and azacytidine-treated cells f) gel electrophoresis of DNA untreated and azacytidine-treated myeloma cells

Azacitidine is a chemical analogue of the nucleoside cytidine, which is present in DNA and RNA. It is thought to have antineoplastic activity via two mechanisms – at low doses, by inhibiting of DNA methyltransferase, causing hypomethylation of DNA,[17] and at high doses, by its direct cytotoxicity to abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA, resulting in cell death. Azacitidine is a ribonucleoside, so it is incorporated into RNA to a larger extent than into DNA. In contrast, decitabine (5-aza-2'-deoxycytidine) is a deoxyribonucleoside, so it can only incorporate into DNA. Azacitidine's incorporation into RNA leads to the disassembly of polyribosomes, defective methylation and acceptor function of transfer RNA, and inhibition of the production of proteins. Its incorporation into DNA leads to covalent binding with DNA methyltransferases, which prevents DNA synthesis and subsequently leads to cytotoxicity. It has been shown effective against human immunodeficiency virus in vitro[18] and human T-lymphotropic virus.[19]

Inhibition of methylation

After azanucleosides such as azacitidine have been metabolized to 5-aza-2′-deoxycytidine-triphosphate (aka, decitabine-triphosphate), they can be incorporated into DNA and azacytosine can be substituted for cytosine. Azacytosine-guanine dinucleotides are recognized as substrate by the DNA methyltransferases, which catalyze the methylation reaction by a nucleophilic attack. This results in a covalent bond between the carbon-6 atom of the cytosine ring and the enzyme. The bond is normally resolved by beta-elimination through the carbon-5 atom, but this latter reaction does not occur with azacytosine because its carbon-5 is substituted by nitrogen, leaving the enzyme covalently bound to DNA and blocking its DNA methyltransferase function. In addition, the covalent protein adduction also compromises the functionality of DNA and triggers DNA damage signaling, resulting in the degradation of trapped DNA methyltransferases. As a consequence, methylation marks become lost during DNA replication.[20][21]


Both drugs were first synthesized in Czechoslovakia.[22]


Azacitidine can be used in vitro to remove methyl groups from DNA. This may weaken the effects of gene silencing mechanisms that occur prior to methylation. Certain methylations are believed to secure DNA in a silenced state, and therefore demethylation may reduce the stability of silencing signals and confer relative gene activation.[23]

Azacitidine induces tumor regression on isocitrate dehydrogenase-1 mutant glioma xenografts in mice.[24]

In research, 5-azacitidine is commonly used for promoting cardiomyocyte differentiation of adult stem cells. However, it has been suggested that this drug has a compromised efficacy as a cardiac differentiation factor because it promotes the transdifferentiation of cardiac cells to skeletal myocytes.[25]

Azacitidine also has antiviral effects in animal studies as well as its anti-cancer actions, but has not been tested for clinical use.[26][27]


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  2. 2.0 2.1 2.2 "Azacitidine". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases. 2012. Archived from the original on 11 December 2021. Retrieved 17 January 2022.
  3. 3.0 3.1 3.2 3.3 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 950. ISBN 978-0857114105.
  4. 4.0 4.1 4.2 4.3 4.4 "DailyMed - VIDAZA- azacitidine injection, powder, lyophilized, for solution". Archived from the original on 5 November 2021. Retrieved 17 January 2022.
  5. "Azacitidine (Vidaza) Use During Pregnancy". 5 May 2020. Archived from the original on 5 December 2020. Retrieved 12 August 2020.
  6. "Onureg EPAR". European Medicines Agency. 20 April 2021. Archived from the original on 6 September 2021. Retrieved 6 September 2021.
  7. 7.0 7.1 7.2 7.3 7.4 7.5 7.6 "Vidaza- azacitidine injection, powder, lyophilized, for solution". DailyMed. 2 March 2020. Archived from the original on 5 November 2021. Retrieved 27 September 2020.
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  9. "Vidaza". Archived from the original on 29 December 2021. Retrieved 17 January 2022.
  10. "Azacitidine Prices, Coupons & Savings Tips - GoodRx". GoodRx. Archived from the original on 20 September 2022. Retrieved 17 January 2022.
  11. "Drug Approval Package: Vidaza (Azacitidine) NDA #050794". U.S. Food and Drug Administration (FDA). 14 July 2004. Archived from the original on 29 March 2021. Retrieved 26 September 2020.
  12. "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". U.S. Food and Drug Administration (FDA). Archived from the original on 24 June 2016. Retrieved 20 May 2016.
  13. Kaminskas E, Farrell AT, Wang YC, Sridhara R, Pazdur R (March 2005). "FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension". The Oncologist. 10 (3): 176–82. doi:10.1634/theoncologist.10-3-176. PMID 15793220.
  14. Estey EH (September 2013). "Epigenetics in clinical practice: the examples of azacitidine and decitabine in myelodysplasia and acute myeloid leukemia". Leukemia. 27 (9): 1803–12. doi:10.1038/leu.2013.173. PMID 23757301.
  15. "CC-486 (Oral Azacitidine) Monotherapy in Patients with Acute Myeloid Leukemia (AML)". Archived from the original on 2019-09-25. Retrieved 2021-09-06.
  16. Subbanna S, Nagre NN, Shivakumar M, Basavarajappa BS (December 2016). "A single day of 5-azacytidine exposure during development induces neurodegeneration in neonatal mice and neurobehavioral deficits in adult mice". Physiology & Behavior. 167: 16–27. doi:10.1016/j.physbeh.2016.08.036. PMC 5159185. PMID 27594097.
  17. Martens UM, ed. (2010). "11 5-Azacytidine/Azacitidine". Small molecules in oncology. Recent Results in Cancer Research. Vol. 184. Heidelberg: Springer. pp. 159–170. doi:10.1007/978-3-642-01222-8. ISBN 978-3-642-01222-8.
  18. Dapp MJ, Clouser CL, Patterson S, Mansky LM (November 2009). "5-Azacytidine can induce lethal mutagenesis in human immunodeficiency virus type 1". Journal of Virology. 83 (22): 11950–8. doi:10.1128/JVI.01406-09. PMC 2772699. PMID 19726509.
  19. Diamantopoulos PT, Michael M, Benopoulou O, Bazanis E, Tzeletas G, Meletis J, Vayopoulos G, Viniou NA (January 2012). "Antiretroviral activity of 5-azacytidine during treatment of a HTLV-1 positive myelodysplastic syndrome with autoimmune manifestations". Virology Journal. 9: 1. doi:10.1186/1743-422X-9-1. PMC 3305386. PMID 22214262.
  20. Stresemann C, Lyko F (July 2008). "Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabine". International Journal of Cancer. 123 (1): 8–13. doi:10.1002/ijc.23607. PMID 18425818. S2CID 14125490.
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  22. Cihák A (1974). "Biological effects of 5-azacytidine in eukaryotes". Oncology. 30 (5): 405–22. doi:10.1159/000224981. PMID 4142650.
  23. Whitelaw E, Garrick D (2005). "Chapter 7: The Epigenome". In Ruvinsky A, Marshall Graves JA (eds.). Mammalian Genomics. Wallingford, U.K.: CABI Publishing. ISBN 0-85199-910-7.
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External links

External sites: