The success of pharmacologic agents in treating a wide variety of acute and chronic diseases is well-documented. Their risks and potential to cause side effects in the patients being treated is equally well-recognized.1 For certain drugs, this risk extends to pharmacists and other health care workers who handle the drugs, even after exposure to only small concentrations.1
The American Society of Health- System Pharmacists (ASHP) first defined a hazardous drug in 1985 as any agent that carried the potential to cause cancer, developmental or reproductive toxicity, or harm to organs in animal or human studies.2 This definition was later adopted by the Occupational Safety and Health Administration (OSHA).3 Whereas hazardous drugs include a variety of agents?among them cancer chemotherapy, antiviral drugs, and hormones? the ASHP/OSHA definition may not accurately reflect the hazardous risks of more-recent agents.1
Therefore, the National Institute for Occupational Safety and Health revised the definition in 2004 to describe any drug exhibiting 1 or more of the following characteristics in humans or animals:
- Teratogenicity or other developmental toxicity
- Reproductive toxicity
- Organ toxicity at low doses
- Structure and toxicity profiles of new drugs mimicking existing drugs already deemed hazardous1
Guidelines for the safe handling of hazardous drugs are well-established in the traditional settings of hospitals and ambulatory clinics. The application of and adherence to these guidelines for oral therapy in nontraditional settings, such as community pharmacies, are not as well-defined, however.1 A recent survey of the comprehensive cancer centers in the United States reveals few safeguards for oral chemotherapy.4
Although this article does not focus solely on safe handling of oral chemotherapy, the lack of a consensus among these centers about safe medication practices for oral chemotherapy highlights the need for guidelines for this group of drugs. In addition, evidence suggests that existing guidelines may be inadequate for protection from hazardous agents, because measurable amounts of some hazardous drugs have been documented in the urine of health care workers who were using safety precautions and in patient-care areas of facilities that were following recommended procedures.5-7
As the approval and use of novel oral agents for the treatment of cancer continue to expand, the numbers and types of health care workers and environments at risk for the adverse effects of hazardous drugs can only increase. Although most guidelines have been developed for handling intravenous chemotherapy in traditional oncology settings, it is apparent that an update to current guidelines is necessary for the handling of oral chemotherapy in the community setting.1
Overview of Potential for Exposure to Hazardous Drugs
Exposure to hazardous agents can occur during the preparation, administration, or disposal of these drugs when health care workers create aerosols, generate dust, clean up spills, or touch contaminated surfaces.1 For pharmacists handling and dispensing oral chemotherapy, a number of activities in these processes may result in exposure through inhalation, skin contact or absorption, or inadvertent ingestion (Table 1).1
Whereas inhalation and skin contact or absorption are the most common routes of exposure from powder or residue from tablets or capsules, unintentional ingestion can occur through hand-to-mouth contact with these powders or residues. The amount and frequency of exposure to hazardous drugs parallels the risk for adverse effects, but no single biological marker has been found to be a reliable predictor of exposure or adverse effects on health.1
Adverse effects of hazardous drugs through occupational exposure were first reported nearly 30 years ago, when an increased incidence of genotoxicity was documented in pharmacists and nurses handling antineoplastic drugs.8,9 Studies also established an association between exposure to chemotherapy drugs and increased fetal loss, congenital malformations, and infertility among health care workers.1 In addition, an increased risk for leukemia among oncology nurses and physicians exposed to antineoplastic drugs was found in a Danish cancer registry.10 Therefore, establishing guidelines and subsequent adherence are essential to safeguarding all health care professionals regardless of practice setting.
Rationale for Community-based Guidelines for Oral Chemotherapy Drugs
Because chemotherapeutic agents have a narrow therapeutic index, medication errors and occupational exposure serve to increase the risk for harmful or potentially lethal effects in patients and health care personnel alike.11,12 Oral agents currently account for less than 5% of all drugs used for cancer treatment, but they are expected to represent up to 25% in the next decade.13 Furthermore, nearly one quarter of the 200 antineoplastic drugs in development are oral agents.12
Therefore, with the increased approval of novel oral agents and the expanding indications for traditional oral chemotherapy for cancer come the potential for increased exposure to pharmacists in both the retail and long-term care settings. A number of issues surround the safe administration and handling of oral chemotherapy agents.11 Unfortunately, current recommendations generally assume that patients will receive chemotherapy in traditional health care settings. The increased use of oral therapy, however, is shifting this paradigm from primarily ambulatory infusion clinics and physician offices to include self-administration at home and in assisted living or long-term care facilities. Such a shift presents additional challenges to safe drug handling and administration.11,13 In many of these settings, oral chemotherapy agents often are dispensed or administered without proper safeguards.11,14
Yet, considering the consequences of unsafe handling, the OSHA guidelines offer limited recommendations regarding the handling of nonliquid hazardous drugs by pharmacists. Current recommendations state that tablets should be counted in a designated biologic safety cabinet, which is not available in the majority of retail pharmacies; manual counting devices should not be used; and automated counting machines should be used only if the handler can be isolated from the hazardous drug.12
In settings outside the hospital or infusion clinic, oral chemotherapy may be administered by patients, family members, or health care personnel without oncology experience.11,12 Both OSHA and the Oncology Nursing Society advise the use of personal protective equipment (PPE) during administration of chemotherapy. Yet, research evidence on the effectiveness of PPE against exposure to oral agents is lacking.11,12,15 Equally important is the fact that individuals in nontraditional chemotherapy settings may not be able to comply with OSHA regulations regarding the use of PPE and the disposal of hazardous waste (eg, gloves, medicine cups) or to readily dispose of any waste of leftover products with licensed waste-disposal companies.11
Despite awareness of the occupational risks for the harmful effects of chemotherapy drugs for more than 20 years, reports continue to document exposure of health care workers.16 Currently, no standardized national guidelines exist for the safe handling of oral chemotherapy agents in either traditional or nontraditional health care settings, and no single institutional policy can serve as an adequate model.
Policies and procedures to reduce risk among all personnel involved in oral chemotherapy treatment?including pharmacists?are essential.14,16 Risk-reduction measures in nontraditional settings should include a 2-person verification system, education of all individuals who will handle and administer oral agents, and procedures for appropriate and secure storage.11
A framework for developing a sample policy for safe handling and administration is suggested in Table 2. This table was synthesized from the available national and institutional guidelines currently available in the United States. Both traditional and nontraditional facilities where oral chemotherapy is handled and dispensed will need to develop individualized policies and procedures to ensure the safe handling and administration of oral chemotherapy agents in a variety of settings by both skilled and untrained personnel. This framework may serve as a foundation for the development and implementation of procedures for the safe handling and administration of oral chemotherapy agents?particularly in nontraditional health care settings? nationwide.
1. Centers for Disease Control and Prevention. National Institute for Occupational Safety and Health. Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings. NIOSH publication 2004-165. September 2004. Available at: www.cdc.gov/niosh/docs/2004-165. Accessed September 14, 2006.
2. American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic drugs in hospitals. Am J Hosp Pharm. 1985;42:131-137.
3. US Department of Labor. Occupational Safety and Health Administration. Work practice guidelines for personnel dealing with cytotoxic (antineoplastic) drugs. OSHA publication 8-1.1. 1986.
4. Weingart SM, Flug J, Brouillard D, et al. Oral chemotherapy safety practices at US cancer centers: questionnaire survey. Brit Med J. 2007;334(7590):407. Epub 2007 Jan 12.
5. Wick C, Slawson MH, Jorgenson JA, Tyler LS. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am J Health Syst Pharm. 2003; 15;60:2314-2320.
6. Sessink PJ, Wittenhorst BC, Anzion RB, Bos RP. Exposure of pharmacy technicians to antineoplastic agents: reevaluation after additional protective measures. Arch Environ Health. 1997;52:240-244.
7. Pethran A, Schierl R, Hauff K, Grimm CH, Boosk S, Nowak D. Uptake of antineoplastic agents in pharmacy and hospital personnel?Pt I: Monitoring of urinary concentrations. Int Arch Occup Environ Health. 2003;76:5-10. Epub 2002 Oct 9.
8. Falck K, Gr?hn P, Sorsa M, Vainio H, Heinonen E, Holsti LR. Mutagenicity in urine of nurses handling cytostatic drugs. Lancet. 1979;1:1250-1251.
9. Anderson RW, Puckett WH Jr, Dana WJ, Nguyen TV, Theiss JC, Matney TS. Risk of handling injectable antineoplastic agents. Am J Hosp Pharm. 1982;39:1881-1887.
10. Skov T, Maarup B, Olsen J, Rorth M, Winthereik H, Lynge E. Leukaemia and reproductive outcome among nurses handling antineoplastic drugs. Br J Ind Med. 1992;49:855-861.
11. Griffin E. Safety considerations and safe handling of oral chemotherapy agents. Clin J Oncol Nurs. 2003;7(suppl):25-29.
12. Birner A. Safe administration of oral chemotherapy. Clin J Oncol Nurs. 2003;7:158-162.
13. Pratt S. The Oncology Roundtable: Oral Anticancer Agents. Implications for Patient Management and Program Economics. The Advisory Board Company. Practice Brief #31. Washington, DC. June 13, 2002.
14. US Department of Labor. Occupational Safety and Health Administration. Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA Technical Manual. Available at: www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html. Accessed September 15, 2006.
15. Ross TW. Oral chemotherapy agents. Hospital Pharmacist Report. March 1999:29-38.
16. Polovich M. Developing a hazardous drug safe-handling program. Community Oncology. 2005;2:403-405.