PEMETREXED

Pemetrexed is used alone or in combination with cisplatin to treat locally advanced or metastatic non-small cell lung cancer in patients. It is also used in combination with cisplatin to treat malignant pleural mesothelioma in patients whose disease is unresectable or who are not candidates for curative surgery (Prod Info ALIMTA(R) intravenous injection powder, 2013).

FORMS

Pemetrexed is available as 100 mg and 500 mg single-use vials for injection (Prod Info ALIMTA(R) intravenous injection powder, 2013).

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

USES: Pemetrexed is used alone or in combination with cisplatin to treat locally advanced or metastatic non-small cell lung cancer in patients. It is also used in combination with cisplatin to treat malignant pleural mesothelioma in patients whose disease is unresectable or who are not candidates for curative surgery.

PHARMACOLOGY: Pemetrexed is an folate analog metabolic inhibitor that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes required for cell replication. In in vitro studies, pemetrexed inhibited thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides.

EPIDEMIOLOGY: Inadvertent iatrogenic overdose may occur, but is rare.

WITH POISONING/EXPOSURE

Pemetrexed administration, in doses of 600 mg/m(2) or greater, have resulted in neutropenia, anemia, thrombocytopenia, nausea, vomiting, diarrhea, and rash. Other possible overdose effects may include infection (with or without fever) and mucositis.

WITH THERAPEUTIC USE

Myelosuppression is the dose-limiting toxicity with pemetrexed therapy. Anemia, leukopenia, neutropenia, thrombocytopenia, immune-mediated hemolytic anemia, and febrile neutropenia have been reported. The most common adverse effects are nausea, anorexia, and fatigue. Other adverse effects include chest pain, hypertension, vomiting, constipation, diarrhea, stomatitis, rash/desquamation, alopecia, edema, Stevens-Johnson syndrome, toxic epidermal necrolysis, radiation recall syndrome, pancreatitis, colitis, elevated liver enzymes, hypersensitivity reactions, rhabdomyolysis, myalgia, arthralgia, sensory neuropathy, dyspnea, pneumonitis, fever, and infection.

Editor's Note: An ERG guide with information appropriate to this material does not exist.

-FIRST AID

FIRST AID AND PREHOSPITAL TREATMENT

Gastrointestinal decontamination is not recommended; administered via the parenteral route.

-RANGE OF TOXICITY

MAXIMUM TOLERATED EXPOSURE

Nausea and vomiting, rash, and grade 3 and 4 neutropenia have been reported following intravenous administration of pemetrexed at a dose of 1200 mg/m(2) (Niyikiza et al, 2002).

Carcinogenicity Ratings for CAS137281-23-3 :

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 IRIS

EPA Risk Assessment Values for CAS137281-23-3 (U.S. Environmental Protection Agency, 2011):

Not Listed

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS137281-23-3 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS137281-23-3 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS137281-23-3 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS137281-23-3 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS137281-23-3 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS137281-23-3 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS137281-23-3 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS137281-23-3 (U.S. Environmental Protection Agency, 2010b):

Not Listed
Editor's Note: The D, F, and K series waste numbers and Appendix VIII to Part 261 -- Hazardous Constituents were not included. Please refer to 40 CFR Part 261.

EPA SARA Title III, Extremely Hazardous Substance List for CAS137281-23-3 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA SARA Title III, Community Right-to-Know for CAS137281-23-3 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS137281-23-3 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS137281-23-3 (EPA, 2005):

Not Listed

LABELS

NFPA

NFPA Hazard Ratings for CAS137281-23-3 (NFPA, 2002):

Not Listed

-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 137281-23-3.

Specific recommendations and test data for this chemical were not found in the available manufacturers' product literature. A complete list of consulted manufacturers and references is presented below.

-PHYSICAL HAZARDS

FIRE HAZARD

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

FLAMMABILITY CLASSIFICATION

NFPA Flammability Rating for CAS137281-23-3 (NFPA, 2002):

Not Listed

FIRE CONTROL/EXTINGUISHING AGENTS

Editor's Note: An ERG guide with information appropriate to this material does not exist.

NFPA Extinguishing Methods for CAS137281-23-3 (NFPA, 2002):

Not Listed

EVACUATION PROCEDURES

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

AIHA ERPG Values for CAS137281-23-3 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS137281-23-3 (U.S. Department of Energy, Office of Emergency Management, 2010):

Not Listed

AEGL Values for CAS137281-23-3 (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; 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; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; United States Environmental Protection Agency Office of Pollution Prevention and Toxics, 2006; 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, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; 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, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; 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, 2005; 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, 2005; 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, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; 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):

Not Listed

NIOSH IDLH Values for CAS137281-23-3 (National Institute for Occupational Safety and Health, 2007):

Not Listed

CONTAINMENT/WASTE TREATMENT OPTIONS

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

SMALL LEAK/SPILL

Editor's Note: An ERG guide with information appropriate to this material does not exist.

LARGE LEAK/SPILL

Editor's Note: An ERG guide with information appropriate to this material does not exist.

-PHYSICAL/CHEMICAL PROPERTIES

MOLECULAR WEIGHT

597.49 (Prod Info ALIMTA(R) injection, 2004)

DESCRIPTION/PHYSICAL STATE

Pemetrexed is a white to light yellow or green-yellow lyophilized powder (Prod Info ALIMTA(R) injection, 2004).

-REFERENCES

GENERAL BIBLIOGRAPHY

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40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.

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65 FR 39264: 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, 2000.

65 FR 77866: 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, 2000.

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Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents