TRASTUZUMAB

Trastuzumab is used alone in patients with metastatic breast cancer whose tumors overexpress the HER2 protein and who have received one or more chemotherapy regimens for their metastatic disease. It is also used in combination with paclitaxel to treat patients with metastatic breast cancer whose tumors overexpress the HER2 protein and who have not received chemotherapy for their metastatic disease (Prod Info HERCEPTIN(R) intravenous solution, 2005).

FORMS

Trastuzumab is available as a lyophilized, sterile powder nominally containing 440 mg Trastuzumab per vial. Reconstitution with the supplied 20 milliliters of Bacteriostatic Water for Injection, USP, containing 1.1% benzyl alcohol as a preservative yields a solution containing 21 mg/mL trastuzumab (Prod Info HERCEPTIN(R) intravenous solution, 2005).

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

USES: Trastuzumab is used alone in patients with metastatic breast cancer whose tumors overexpress the HER2 protein and who have received one or more chemotherapy regimens for their metastatic disease. It has also been used in combination with other chemotherapeutic agents (ie, paclitaxel, docetaxel, cisplatin and capecitabine or 5-fluorouracil (5-FU), doxorubicin, cyclophosphamide) to treat patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, as adjuvant breast cancer therapy or in metastatic breast cancer.

PHARMACOLOGY: In some patients with breast cancer and other malignancies (eg; ovarian, lung), trastuzumab, a recombinant DNA-derived humanized monoclonal antibody, selectively binds with high affinity to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER2). The antibody is an IgG1 kappa that contains human framework regions with murine antibody (4D5) complementarity-determining regions. Trastuzumab causes antibody-dependent cell-mediated cytotoxicity (ADCC) and does not affect cells not overexpressing p185-HER2.

EPIDEMIOLOGY: Overdose is uncommon.

WITH POISONING/EXPOSURE

OVERDOSE: Limited data. The signs and symptoms of an acute overdose are expected to be similar to excessive pharmacologic effects.
MILD TO MODERATE TOXICITY: Nausea, vomiting, abdominal pain, diarrhea, fever, infusion reactions, headache, fatigue, dyspnea, rash, and myalgia may develop.
SEVERE TOXICITY: Cardiotoxicity (ie, congestive heart failure, cardiomyopathy, dysrhythmias) may develop following a significant exposure. Pulmonary toxicity and serious or fatal infusion reactions may occur.

WITH THERAPEUTIC USE

CARDIOVASCULAR: Severe ventricular dysfunction and congestive heart failure have been reported following trastuzumab administration. The incidence and severity of cardiac dysfunction is higher in patients 60 years of age and older, patients who have received cardiotoxic therapy (anthracyclines [a cumulative anthracycline dose equal or greater than 400 mg/m(2)], cyclophosphamide), prior chest wall radiation, and preexisting cardiac disease. Peripheral edema and hypotension have also been reported.
HEMATOLOGIC: Myelosuppression is infrequent following the administration of trastuzumab as a single agent. An increase in anemia, leukopenia, grade 3/4 neutropenia or febrile neutropenia have been observed in patients treated with trastuzumab and other chemotherapeutic agents (ie, capecitabine, 5-FU, cisplatin).
RESPIRATORY: Cough, dyspnea, rhinitis, sinusitis, bronchospasm, pleural effusions, pulmonary infiltrates, acute lung injury, and pulmonary insufficiency and hypoxia have occurred with trastuzumab.
OTHER: Other events include: nausea, vomiting, abdominal pain, diarrhea, fever, infusion reactions, headache, fatigue, dyspnea, rash, acne, renal dysfunction, asthenia, headache, and insomnia may develop.
RARE: Rare cases of severe infusion reactions (ie, anaphylaxis, bronchospasm, angioedema and/or hypotension), including some fatalities have occurred with trastuzumab administration. Symptoms usually occurred during the infusion or within 24 hours of administration. Fever and chills are common during an infusion. Other flu-like symptoms reported during/after an infusion include: headache, nausea, vomiting, back pain, asthenia, rigors, dizziness, hypotension, and rash.

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 necessary as trastuzumab is administered IV.

-RANGE OF TOXICITY

MAXIMUM TOLERATED EXPOSURE

No lethal human dose has been reported. Single doses higher than 8 mg/kg have not been administered (Prod Info HERCEPTIN(R) intravenous infusion, 2010).

Carcinogenicity Ratings for CAS180288-69-1 :

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 CAS180288-69-1 (U.S. Environmental Protection Agency, 2011):

Not Listed

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS180288-69-1 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS180288-69-1 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS180288-69-1 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS180288-69-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS180288-69-1 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS180288-69-1 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS180288-69-1 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS180288-69-1 (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 CAS180288-69-1 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA SARA Title III, Community Right-to-Know for CAS180288-69-1 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS180288-69-1 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS180288-69-1 (EPA, 2005):

Not Listed

LABELS

NFPA

NFPA Hazard Ratings for CAS180288-69-1 (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 180288-69-1.

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 CAS180288-69-1 (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 CAS180288-69-1 (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 CAS180288-69-1 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS180288-69-1 (U.S. Department of Energy, Office of Emergency Management, 2010):

Not Listed

AEGL Values for CAS180288-69-1 (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 CAS180288-69-1 (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

TRASTUZUMAB: 148 kilodaltons (Prod Info HERCEPTIN(R) intravenous solution, 2005)

DESCRIPTION/PHYSICAL STATE

TRASTUZUMAB: A sterile, white to pale yellow, preservative-free lyophilized powder (Prod Info HERCEPTIN(R) intravenous injection, 2014).

Approximately 6: when reconstituted with bacteriostatic water for injection or sterile water for injection (Prod Info HERCEPTIN(R) intravenous injection, 2014).

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GENERAL BIBLIOGRAPHY

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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.

66 FR 21940: 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, 2001.

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Product Information: HERCEPTIN(R) intravenous infusion powder, trastuzumab intravenous infusion powder. Genentech, Inc. (per manufacturer), South San Francisco, CA, 2016.

Product Information: HERCEPTIN(R) intravenous infusion, trastuzumab intravenous infusion. Genentech, Inc., South San Francisco, CA, 2010.

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TRASTUZUMAB

Classification | Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents