AZACITIDINE
HAZARDTEXT ®
Information to help in the initial response for evaluating chemical incidents
-IDENTIFICATION
SYNONYMS
4-Amino-1-beta-D-ribofuranosyl-1,3,5-triazin-2(1H)-one s-Triazin-2(1H)-one, 4-amino-1-beta-D-ribofuranosyl-(8CI) Azacitidina 5-Azacytidine AZA-CR Ladakamycin NCI-C01569 NSC-102816 U-18496 WR-183027
IDENTIFIERS
USES/FORMS/SOURCES
Azacitidine is indicated for the treatment of various myelodysplastic syndrome subtypes including refractory anemia with or without 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 (Prod Info VIDAZA(R) subcutaneous injection, intravenous injection, 2012).
-CLINICAL EFFECTS
GENERAL CLINICAL EFFECTS
- USES: Azacitidine is indicated for the treatment of various myelodysplastic syndrome subtypes including refractory anemia with or without 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.
- PHARMACOLOGY: Appears to restore normal growth and differentiation of bone marrow cells by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. Hypomethylation may permit the normal functioning of genes that regulate differentiation and proliferation.
- EPIDEMIOLOGY: Overdoses are rare.
MILD TO MODERATE TOXICITY: Gastrointestinal effects (nausea, vomiting, diarrhea) occurred following administration of a single IV dose of approximately 290 mg/m(2), approximately 4 times the recommended starting dose. SEVERE TOXICITY: Severe toxicity following overdose has not been reported. It is anticipated that clinical effects will likely be an extension of adverse events (ie, myelosuppression, fatigue, nausea, vomiting, diarrhea).
COMMON: The most commonly occurring events (greater than 30%) following use include effects related to myelosuppression (ie, neutropenia, thrombocytopenia, anemia), fatigue, pyrexia, gastrointestinal symptoms (ie, nausea, vomiting, constipation or diarrhea), injection site reactions, petechiae, and hypokalemia. LESS FREQUENT: Other effects occurring less frequently include hypotension, myocarditis, mucositis, renal dysfunction, hepatic abnormalities, myalgias, rhabdomyolysis, headache, dyspnea, and coma.
- Editor's Note: An ERG guide with information appropriate to this material does not exist.
-FIRST AID
FIRST AID AND PREHOSPITAL TREATMENT
- Decontamination is not necessary; azacitidine is administered parenterally.
-RANGE OF TOXICITY
MAXIMUM TOLERATED EXPOSURE
- During a clinical trial, nausea, vomiting, and diarrhea occurred in one patient who received a single IV azacitidine dose of 290 mg/m(2) (approximately 4 times the recommended starting dose). The patient recovered without sequelae (Prod Info VIDAZA(R) subcutaneous injection, intravenous injection, 2012).
- Carcinogenicity Ratings for CAS320-67-2 :
ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed EPA (U.S. Environmental Protection Agency, 2011): Not Listed IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 2A ; Listed as: Azacitidine 2A : The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.
NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed MAK (DFG, 2002): Not Listed NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): R ; Listed as: Azacitidine (5-Azacytidine)
TOXICITY AND RISK ASSESSMENT VALUES
- EPA Risk Assessment Values for CAS320-67-2 (U.S. Environmental Protection Agency, 2011):
-STANDARDS AND LABELS
WORKPLACE STANDARDS
- ACGIH TLV Values for CAS320-67-2 (American Conference of Governmental Industrial Hygienists, 2010):
- AIHA WEEL Values for CAS320-67-2 (AIHA, 2006):
- NIOSH REL and IDLH Values for CAS320-67-2 (National Institute for Occupational Safety and Health, 2007):
- OSHA PEL Values for CAS320-67-2 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
- OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS320-67-2 (U.S. Occupational Safety and Health Administration, 2010):
ENVIRONMENTAL STANDARDS
- EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS320-67-2 (U.S. Environmental Protection Agency, 2010):
- EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS320-67-2 (U.S. Environmental Protection Agency, 2010):
- EPA RCRA Hazardous Waste Number for CAS320-67-2 (U.S. Environmental Protection Agency, 2010b):
- EPA SARA Title III, Extremely Hazardous Substance List for CAS320-67-2 (U.S. Environmental Protection Agency, 2010):
- EPA SARA Title III, Community Right-to-Know for CAS320-67-2 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):
- DOT List of Marine Pollutants for CAS320-67-2 (49 CFR 172.101 - App. B, 2005):
- EPA TSCA Inventory for CAS320-67-2 (EPA, 2005):
LABELS
- NFPA Hazard Ratings for CAS320-67-2 (NFPA, 2002):
-PERSONAL PROTECTION
SUMMARY
- Editor's Note: An ERG guide with information appropriate to this material does not exist.
PROTECTIVE CLOTHING
- CHEMICAL PROTECTIVE CLOTHING. Search results for CAS 320-67-2.
-PHYSICAL HAZARDS
FIRE HAZARD
- FLAMMABILITY CLASSIFICATION
- NFPA Flammability Rating for CAS320-67-2 (NFPA, 2002):
- FIRE CONTROL/EXTINGUISHING AGENTS
- Editor's Note: An ERG guide with information appropriate to this material does not exist.
- NFPA Extinguishing Methods for CAS320-67-2 (NFPA, 2002):
EVACUATION PROCEDURES
- Editor's Note: An ERG guide with information appropriate to this material does not exist.
- AIHA ERPG Values for CAS320-67-2 (AIHA, 2006):
- DOE TEEL Values for CAS320-67-2 (U.S. Department of Energy, Office of Emergency Management, 2010):
- AEGL Values for CAS320-67-2 (National Research Council, 2010; National Research Council, 2009; National Research Council, 2008; National Research Council, 2007; NRC, 2001; NRC, 2002; NRC, 2003; NRC, 2004; NRC, 2004; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; 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62 FR 58840, 1997; 65 FR 14186, 2000; 65 FR 39264, 2000; 65 FR 77866, 2000; 66 FR 21940, 2001; 67 FR 7164, 2002; 68 FR 42710, 2003; 69 FR 54144, 2004):
- NIOSH IDLH Values for CAS320-67-2 (National Institute for Occupational Safety and Health, 2007):
CONTAINMENT/WASTE TREATMENT OPTIONS
-PHYSICAL/CHEMICAL PROPERTIES
MOLECULAR WEIGHT
- 244 (Prod Info VIDAZA(R) injection, 2008)
DESCRIPTION/PHYSICAL STATE
- Azacitidine is a white to off-white solid that is soluble in dimethylsulfoxide; sparingly soluble in water, water-saturated octanol, 5% dextrose in water, N-methyl-2-pyrrolidone, normal saline, and 5% Tween 80 in water; slightly soluble in ethanol/water (50/50), propylene glycol, and polyethylene glycol; and insoluble in acetone, ethanol, and methyl ethyl ketone (Prod Info VIDAZA(R) injection, 2008).
SOLUBILITY
Dimethylsulfoxide: Soluble; Water saturated octanol: Sparingly soluble; 5% dextrose in water: Sparingly soluble; N-methyl-2-pyrrolidone: Sparingly soluble; Normal saline: Sparingly soluble; 5% Tween 80 in water: Sparingly soluble; Ethanol/water (50/50): Slightly soluble; Propylene glycol: Slightly soluble; Polyethylene glycol: Slightly soluble; Acetone: Insoluble; Ethanol: Insoluble; Methyl ethyl ketone: insoluble (Prod Info VIDAZA(R) injection, 2008)
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- 69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.
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- Product Information: COMPAZINE(R) tablets, injection, suppositories, syrup, prochlorperazine tablets, injection, suppositories, syrup. GlaxoSmithKline, Research Triangle Park, NC, 2004.
- Product Information: Compazine(R), prochlorperazine maleate spansule. GlaxoSmithKline, Research Triangle Park, NC, 2002.
- Product Information: KEPIVANCE(TM) IV injection, palifermin IV injection. Amgen Inc, Thousand Oaks, CA, 2005.
- Product Information: NEUPOGEN(R) IV, subcutaneous injection, filgrastim IV, subcutaneous injection. Amgen Manufacturing, Thousand Oaks, CA, 2010.
- Product Information: VIDAZA(R) injection, azacitidine injection. Celgene Corporation, Summit, NJ, 2008.
- Product Information: VIDAZA(R) subcutaneous injection, intravenous injection, azacitidine subcutaneous injection, intravenous injection. Celgene Corporation (per FDA), Summit, NJ, 2012.
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