ASHP Technical Assistance Bulletin On Handling Cytotoxic and Hazardous Drugs
ASHP Technical Assistance Bulletin On Handling Cytotoxic and Hazardous Drugs
ASHP Technical Assistance Bulletin On Handling Cytotoxic and Hazardous Drugs
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The oncogenic and teratogenic effects of therapeutic doses of several antineoplastic agents are well established.913 The mutagenic properties of some cytotoxics, immunosuppressants, antiviral agents, and biological response modifiers have also been documented.14 The longterm effects (e.g., cancer, impaired fertility, and organ damage) of continued exposure to small amounts of one or more of such drugs remain undetermined. For example, it is known that long-term use of potent immunosuppressive agents may result in the development of lymphoma. It is not known, however, at what drug level or over what period of time this may occur and how this correlates with possible drug levels achieved through occupational exposure during preparation and administration of hundreds or thousands of injectable and oral doses of these agents. Studies have attempted to assess indirectly the potential exposure of hospital pharmacists and nurses to some hazardous drugs in several health-care settings including physicians offices.1521 These studies examined the urine mutagenicity or evidence of chromosome damage in subjects who prepared or administered primarily antineoplastic injections. The mutagenicity and chromosome damage that were found were thought to document exposure to and absorption of the drugs that had been handled. An association may exist between carcinogenicity and chromosome breakage or mutagenicity. Therefore, one might conclude that handling hazardous drugs entails some danger to health-care personnel. These studies, although not conclusive, support the postulated occupational risks. However, several reports make the situation slightly more ominous. Palmer and coworkers22 measured chromosome damage in 10 patients receiving chlorambucil. They found that the damage was cumulative and was related to both the daily dose and the duration of therapy. Another report23 described permanent liver damage in three nurses who had worked 6, 8, and 16 years, respectively, on an
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Safety Precautions
Ideally, the safety precautions employed to protect healthcare workers handling hazardous drugs would be those whose efficacy and cost-effectiveness have been documented. Since these drugs have many different physical and chemical properties, research studies into environmental contamination and safety-garment penetration for all questionable drugs are problematic. However, several studies have attempted to demonstrate the effectiveness of certain recommended interventions. Hoy and Stump42 concluded that a commercial air-venting device, when used with appropriate technique, effectively reduced the release of drug aerosols during reconstitution of drugs packaged in vials. A study by Anderson et al.16 provides support for preparing hazardous drugs in a vertical laminar airflow biological safety cabinet (BSC) (NSF Class II;43 see Appendix B) rather than a horizontal airflow clean air work station. A more recent air-sampling study,44 carried out in a hospital pharmacy work area where a Class II BSC was used to prepare cytotoxic drugs, detected no fluorouracil during the study period. The study was limited to one drug and two short study periods; the results indicate that a Class II BSC, in conjunction with stringent aseptic technique and recommended procedures for handling hazardous drugs, may reduce environmental contamination by these drugs. While common sense suggests that the airflow characteristics of containment cabinets would provide greater worker protection than open airflow workstations, it should also suggest that the front opening of the Class II BSC might present potential for environmental contamination and increased worker exposure to hazardous agents. Indeed, as demonstrated by an industrial hygiene experiment,45 a Class II BSC may cause occasional leakage toward the operator and into the environment if it is placed in an area of strong air drafts or frequent personnel traffic. The containment characteristics of the Class II BSC are compromised whenever the intake or exhaust grilles are blocked (e.g., by placing equipment or supplies on the front grille or too near the back exhaust) or by too much movement on the part of the operator. Gloves are a major source of protection, whether the work is performed with or without a Class II BSC. The permeability of various glove materials to selected drugs has been examined.4649 By using various methods to determine and quantitate penetration, researchers found that permeability of the glove material varied with the drug, contact time, and glove thickness. None of the glove materials tested was impervious to all drugs, and no material was statistically superior except as related to thickness. A thicker glove material is optimal. In addition, several glove materials showed variation in permeability within a manufacturers lot. These studies do establish that gloves can provide protection against skin contact with the tested drugs, although the degree of protection has not been substantiated. Protection from skin contact is important since many of the problem drugs are skin irritants or even vesicants and, as Hirst et al.30 showed, at least one (cyclophosphamide) is absorbed through the skin. Only one study50 looked at the permeability of gown
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The handling of hazardous drugs is a complex issue, and the advice of medical experts, occupational physicians, industrial hygienists, legal counsel, and others should be obtained when organizational policy is being established. Goal I. Accidental contamination of the health-care environment, resulting in exposure of personnel, patients, visitors, and family members to hazardous substances, is prevented by maintaining the physical integrity and security of packages of hazardous drugs. 1. 2. Access to all areas where hazardous drugs are stored is limited to specified authorized staff. A method should be present for identifying to personnel those drugs that require special precautions (e.g., cytotoxics).52 One way to accomplish this is to apply appropriate warning labels (see Figure 1) to all hazardous drug containers, shelves, and bins where the drug products are stored.
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Figure 1. One example of a suitable warning label for cytotoxic and hazardous drugs. Other labels may be used.
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Goal III. Procedures for administering hazardous drugs prevent the accidental exposure of patients and staff and contamination of the work environment. 1. A method for informing and training health-care professionals in these procedures is maintained. a. Only individuals trained to administer hazardous drugs should be allowed to perform this function. Training programs should contain information on the therapeutic and adverse effects of these
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Goal IV. The health-care setting, its staff, patients, contract workers, visitors, and the outside environment are not exposed to or contaminated with hazardous drug waste materials produced in the course of using these drugs. (See Figure 2 for proposed flow chart for handling contaminated items.) 1. Written policies and procedures governing the identification, containment, collection, segregation, and disposal of hazardous drug waste materials are established and maintained. All health-care workers who handle hazardous drugs or waste must be oriented to and must follow these procedures. Throughout institutional health-care facilities and in alternative health-care settings, hazardous drug waste materials are identified, contained, and segregated from all other trash. a. Hazardous drug waste should be placed in specially marked (specifically labeled CAUTION: HAZARDOUS CHEMICAL WASTE) thick plastic bags or leakproof containers. These receptacles should be kept in all areas where the drugs are commonly used. All and only hazardous drug waste should be placed in them. Receptacles used for glass fragments, needles, and syringes should be puncture resistant. Hazardous drug waste should not be mixed with any other waste. Waste containers should be handled with uncontaminated gloves. b. Health-care personnel providing care in a patients home should have with them all the equipment and supplies necessary to contain properly any hazardous drug waste that is generated during the visit. Contaminated needles and syringes, intravenous containers, intravenous sets, and any
Item is contaminated with hazardous material Item is to be reused
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Item is to be discarded
Is it infectious? Yes
Disinfect it (bleach, autoclave, etc.)
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Figure 2. Proposed flow chart for handling chemical hazards versus biohazards. Disinfection of a disposable item contaminated with both infectious and hazardous material may not be necessary, depending on the degree of infectious hazard (e.g., human immunodeficiency virus versus Escherichia coli) and depending on the method of disposal (e.g., burial versus incineration).
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References
1. American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic drugs in hospitals. Am J Hosp Pharm. 1985; 42:131 7. Yodaiken R. Safe handling of cytotoxic drugs by health care personnel. Washington, DC: Occupational Safety and Health Administration; 1986 Jan 29. (Instructional publication 8-1.1). U.S. Public Health Service, National Institutes of Health. Recommendations for the safe handling of parenteral antineoplastic drugs. Washington, DC: U.S. Department of Health and Human Services; 1983. (NIH publication 83-2621). Recommendations for handling cytotoxic agents. Providence, RI: National Study Commission on Cytotoxic Exposure; 1987 Sep. AMA Council on Scientific Affairs. Guidelines for handling parenteral antineoplastics. JAMA. 1985; 253:15902. Scott SA. Antineoplastic drug information and handling guidelines for office-based physicians. Am J Hosp Pharm. 1984; 41:24023. Barstow J. Safe handling of cytotoxic agents in the home. Home Healthc Nurse. 1986; 3:467. Barry LK, Booher RB. Promoting the responsible handling of antineoplastic agents in the community. Oncol Nurs Forum. 1985; 12:406. Berk PD, Goldberg JD, Silverstein MN, et al. In-
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Appendix AGlossary
Biohazard: An infectious agent presenting a real or potential risk to humans and the environment. Carcinogen: Any cancer-producing substance. Chemotherapy: The treatment of disease by chemical means; first applied to use of chemicals that affect the causative organism unfavorably but do not harm the patient; currently used to describe drug (chemical) therapy of neoplastic diseases (cancer). Clastogenic: Giving rise to or inducing disruption or breakage, as of chromosomes. Contamination: The deposition of potentially dangerous material where it is not desired, particularly where its presence may be harmful or constitute a hazard. Cytotoxic: Possessing a specific destructive action on certain cells; used commonly in referring to antineoplastic drugs that selectively kill dividing cells. Decontamination: Removal, neutralization, or destruction of a toxic (harmful) agent. Exposure: The condition of being subjected to something, as to chemicals, that may have a harmful effect. Acute exposure is exposure of short duration, usually exposure of heavy intensity; chronic exposure is long-term exposure, either continuous or intermittent, usually referring to exposure of low intensity. Genotoxic: Damaging to DNA; pertaining to agents (radiation or chemical substances) known to damage DNA, thereby causing mutations or cancer. Hazardous: Dangerous; risky; representing a health risk. Mutagen: Chemical or physical agent that induces or increases genetic mutations by causing changes in DNA. Plenum: Space within a biohazard cabinet where air flows;
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Class III: A totally enclosed, ventilated cabinet of gas-tight construction. Operations in the cabinet are conducted through attached rubber gloves. The cabinet is maintained under negative air pressure of at least 0.5 inch (12.7 mm) water gauge (wg). Supply air is drawn into the cabinet through HEPA filters. The exhaust air is treated by double HEPA filtration or by HEPA filtration and incineration.
This Technical Assistance Bulletin was reviewed in 1996 by the Council on Professional Affairs and by the ASHP Board of Directors and was found to still be appropriate. Revised by ASHPs Clinical Affairs Department in collaboration with Luci A. Power, M.S., Senior Consultant, Power Enterprises, San Francisco, CA. Reviewed by the officers of the ASHP Special Interest Group (SIG) on Oncology Pharmacy Practice and approved by the ASHP Council on Professional Affairs, September 20, 1989. Approved by the ASHP Board of Directors, November 1516, 1989. Supersedes a previous version approved by the Board of Directors on November 14, 1984. Copyright 1990, American Society of Hospital Pharmacists, Inc. All rights reserved. The bibliographic citation for this document is as follows: American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm. 1990; 47:103349.