CLADRIBINE
HAZARDTEXT ®
Information to help in the initial response for evaluating chemical incidents
-IDENTIFICATION
SYNONYMS
IDENTIFIERS
USES/FORMS/SOURCES
Cladribine is FDA approved for the treatment of active hairy cell leukemia as defined by the presence of clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms (Prod Info cladribine intravenous injection, 2014).
-CLINICAL EFFECTS
GENERAL CLINICAL EFFECTS
- USES: Cladribine is FDA approved for the treatment of active hairy cell leukemia as defined by the presence of clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms.
- PHARMACOLOGY: Cladribine is considered a prodrug, making intracellular phosphorylation necessary for cytotoxic effects to occur. Cladribine passively crosses the cell membrane and in cells with a high ratio of deoxycytidine kinase to deoxynucleotidase, it is phosphorylated by deoxycytidine kinase to 2-chloro-2'-deoxy-beta-D-adenosine monophosphate (2-CdAMP). Since cladribine is resistant to deamination by adenosine deaminase and there is little deoxynucleotide deaminase in lymphocytes and monocytes, the phosphorylated metabolites accumulate intracellularly. Subsequently, 2-CdAMP is converted into triphosphate deoxynucleotide (2-CdATP). Cells containing high concentrations of deoxynucleotides are unable to properly repair single-strand DNA breaks. The broken ends of DNA activate the enzyme poly (ADP-ribose) polymerase resulting in NAD and ATP depletion and disruption of cellular metabolism.
- EPIDEMIOLOGY: Overdose is rare.
Cladribine overdose information is limited. Severe myelosuppression, irreversible paraparesis/quadriparesis, peripheral polyneuropathy, and acute nephrotoxicity have been associated with high doses of cladribine.
COMMON: Commonly reported adverse effects, with an incidence of greater than 20%, include myelosuppression, fever, fatigue, nausea, rash, headache, and infection. Myelosuppression is the dose-limiting toxicity of cladribine. Its duration may be prolonged after discontinuation of therapy. INFREQUENT: Adverse effects that were reported less frequently with cladribine therapy include: tachycardia, edema, diaphoresis, petechiae, epistaxis, vomiting, anorexia, diarrhea, abdominal pain, constipation, myalgia, arthralgia, dizziness, insomnia, asthenia, cough, dyspnea, injection site reactions, and elevated liver enzymes. RARE: Tumor lysis syndrome has been rarely reported.
- 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 in most situations as cladribine is administered IV.
-RANGE OF TOXICITY
MINIMUM LETHAL EXPOSURE
- PEDIATRIC: Irreversible myelosuppression and fatal systemic bacterial or fungal infections occurred in 3 of 7 pediatric patients (1- to 21- years-old with relapsed acute leukemia) who received cladribine, 10.7 mg/m(2)/day for 5 days (2 times the recommended dose for treatment of hairy cell leukemia), during a phase I study (Prod Info cladribine intravenous injection, 2014).
MAXIMUM TOLERATED EXPOSURE
- During a phase I clinical trial, 21 patients received cladribine at doses of 0.10, 0.15, or 0.20 mg/kg/day as a 7-day continuous intravenous infusion for treatment of solid tumors. Following the second course of therapy, one of seven patients developed grade 4 thrombocytopenia at the 0.10 mg/kg/day dose level, and at the 0.15 mg/kg/day dose level, grade 4 thrombocytopenia was reported in 2 patients and grade 3 and 4 neutropenia were reported in 3 and 2 patients, respectively. The results of this study indicated that the maximum tolerated doses of cladribine for the treatment of solid tumors is 0.10 mg/kg/day administered as a 7-day continuous intravenous infusion (Guchelaar et al, 1994).
- Renal dysfunction, including anuria and elevated serum creatinine levels, was reported in 19% of the patients (n=31) within 7 to 13 days after beginning high-dose cladribine therapy (4 to 9 times the recommended dose for treatment of hairy cell leukemia) as a continuous infusion. Several patients were also receiving other medications with a potential for nephrotoxicity. The renal dysfunction appeared to be reversible in two of the patients (Prod Info cladribine intravenous injection, 2014).
- During a dose escalation study, axonal peripheral polyneuropathy was reported following high-dose cladribine therapy at doses of 19 to 21 mg/m(2)/day (approximately 4 times the recommended dose indicated for the treatment of hairy cell leukemia) (Prod Info cladribine intravenous injection, 2014; Vahdat et al, 1994).
- In a study comparing a dosing schedule of 0.12 mg/kg/day for 5 days (repeated monthly) to 0.12 mg/kg once a week for 6 weeks, no significant differences in rates of infection, neutropenia, anemia, or death were observed (Robak et al, 2007).
- Carcinogenicity Ratings for CAS4291-63-8 :
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): Not Listed 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 ): Not Listed
TOXICITY AND RISK ASSESSMENT VALUES
- EPA Risk Assessment Values for CAS4291-63-8 (U.S. Environmental Protection Agency, 2011):
-STANDARDS AND LABELS
WORKPLACE STANDARDS
- ACGIH TLV Values for CAS4291-63-8 (American Conference of Governmental Industrial Hygienists, 2010):
- AIHA WEEL Values for CAS4291-63-8 (AIHA, 2006):
- NIOSH REL and IDLH Values for CAS4291-63-8 (National Institute for Occupational Safety and Health, 2007):
- OSHA PEL Values for CAS4291-63-8 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
- OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS4291-63-8 (U.S. Occupational Safety and Health Administration, 2010):
ENVIRONMENTAL STANDARDS
- EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS4291-63-8 (U.S. Environmental Protection Agency, 2010):
- EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS4291-63-8 (U.S. Environmental Protection Agency, 2010):
- EPA RCRA Hazardous Waste Number for CAS4291-63-8 (U.S. Environmental Protection Agency, 2010b):
- EPA SARA Title III, Extremely Hazardous Substance List for CAS4291-63-8 (U.S. Environmental Protection Agency, 2010):
- EPA SARA Title III, Community Right-to-Know for CAS4291-63-8 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):
- DOT List of Marine Pollutants for CAS4291-63-8 (49 CFR 172.101 - App. B, 2005):
- EPA TSCA Inventory for CAS4291-63-8 (EPA, 2005):
LABELS
- NFPA Hazard Ratings for CAS4291-63-8 (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 4291-63-8.
-PHYSICAL HAZARDS
FIRE HAZARD
- FLAMMABILITY CLASSIFICATION
- NFPA Flammability Rating for CAS4291-63-8 (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 CAS4291-63-8 (NFPA, 2002):
EVACUATION PROCEDURES
- Editor's Note: An ERG guide with information appropriate to this material does not exist.
- AIHA ERPG Values for CAS4291-63-8 (AIHA, 2006):
- DOE TEEL Values for CAS4291-63-8 (U.S. Department of Energy, Office of Emergency Management, 2010):
- AEGL Values for CAS4291-63-8 (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 CAS4291-63-8 (National Institute for Occupational Safety and Health, 2007):
CONTAINMENT/WASTE TREATMENT OPTIONS
-PHYSICAL/CHEMICAL PROPERTIES
MOLECULAR WEIGHT
DESCRIPTION/PHYSICAL STATE
- Cladribine is a clear, colorless, sterile, preservative-free, isotonic solution, with a pH range of 5.5 to 8 (Prod Info cladribine injection, 2005)
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- Product Information: COMPAZINE(R) oral tablets, prochlorperazine maleate oral tablets. PBM Pharmaceuticals, Inc. (per DailyMed), Charlottesville, VA, 2013.
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- Product Information: LEUSTATIN(R) intravenous injection, cladribine intravenous injection. Centocor Ortho Biotech Products, L.P. (per FDA), Raritan, NJ, 2012.
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