Dr. Goodin is the director of the division of pharmaceutical sciences at the Cancer Institute of New Jersey and associate professor of medicine, division of medical oncology, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, New Brunswick.
The success of pharmacologicagents in treating a wide varietyof acute and chronic diseases iswell-documented. Their risks and potentialto cause side effects in the patientsbeing treated is equally well-recognized.1For certain drugs, this risk extends topharmacists and other health care workerswho handle the drugs, even afterexposure to only small concentrations.1
The American Society of Health-System Pharmacists (ASHP) first defineda hazardous drug in 1985 as any agentthat carried the potential to cause cancer,developmental or reproductive toxicity,or harm to organs in animal or humanstudies.2 This definition was later adoptedby the Occupational Safety and HealthAdministration (OSHA).3 Whereas hazardousdrugs include a variety ofagents?among them cancer chemotherapy,antiviral drugs, and hormones?the ASHP/OSHA definition may not accuratelyreflect the hazardous risks ofmore-recent agents.1
Therefore, the National Institute forOccupational Safety and Health revisedthe definition in 2004 to describe anydrug exhibiting 1 or more of the followingcharacteristics in humans or animals:
Guidelines for the safe handling of hazardousdrugs are well-established in thetraditional settings of hospitals andambulatory clinics. The application of andadherence to these guidelines for oraltherapy in nontraditional settings, suchas community pharmacies, are not aswell-defined, however.1 A recent surveyof the comprehensive cancer centers inthe United States reveals few safeguardsfor oral chemotherapy.4
Although this article does not focussolely on safe handling of oralchemotherapy, the lack of a consensusamong these centers about safe medicationpractices for oral chemotherapyhighlights the need for guidelines for thisgroup of drugs. In addition, evidence suggeststhat existing guidelines may beinadequate for protection from hazardousagents, because measurableamounts of some hazardous drugs havebeen documented in the urine of healthcare workers who were using safety precautionsand in patient-care areas offacilities that were following recommendedprocedures.5-7
As the approval and use of novel oralagents for the treatment of cancer continueto expand, the numbers and typesof health care workers and environmentsat risk for the adverse effects of hazardousdrugs can only increase. Althoughmost guidelines have been developed forhandling intravenous chemotherapy intraditional oncology settings, it is apparentthat an update to current guidelines isnecessary for the handling of oralchemotherapy in the community setting.1Overview of Potential for Exposureto Hazardous Drugs
Exposure to hazardous agents canoccur during the preparation, administration,or disposal of these drugs whenhealth care workers create aerosols,generate dust, clean up spills, or touchcontaminated surfaces.1 For pharmacistshandling and dispensing oral chemotherapy, a number of activities in these processesmay result in exposure throughinhalation, skin contact or absorption, orinadvertent ingestion (Table 1).1
Whereas inhalation and skin contact orabsorption are the most common routesof exposure from powder or residuefrom tablets or capsules, unintentionalingestion can occur through hand-to-mouthcontact with these powders orresidues. The amount and frequency ofexposure to hazardous drugs parallelsthe risk for adverse effects, but no singlebiological marker has been found to be areliable predictor of exposure or adverseeffects on health.1
Adverse effects of hazardous drugsthrough occupational exposure werefirst reported nearly 30 years ago, whenan increased incidence of genotoxicitywas documented in pharmacists andnurses handling antineoplastic drugs.8,9Studies also established an associationbetween exposure to chemotherapydrugs and increased fetal loss, congenitalmalformations, and infertility amonghealth care workers.1 In addition, anincreased risk for leukemia among oncologynurses and physicians exposed toantineoplastic drugs was found in aDanish cancer registry.10 Therefore,establishing guidelines and subsequentadherence are essential to safeguardingall health care professionals regardlessof practice setting.Rationale for Community-basedGuidelines for Oral ChemotherapyDrugs
Because chemotherapeutic agentshave a narrow therapeutic index, medicationerrors and occupational exposureserve to increase the risk for harmful orpotentially lethal effects in patients andhealth care personnel alike.11,12 Oralagents currently account for less than5% of all drugs used for cancer treatment,but they are expected to representup to 25% in the next decade.13 Furthermore,nearly one quarter of the 200antineoplastic drugs in development areoral agents.12
Therefore, with the increased approvalof novel oral agents and the expandingindications for traditional oral chemotherapyfor cancer come the potential forincreased exposure to pharmacists inboth the retail and long-term care settings.A number of issues surround the safeadministration and handling of oralchemotherapy agents.11 Unfortunately,current recommendations generally assumethat patients will receive chemotherapyin traditional health care settings.The increased use of oral therapy,however, is shifting this paradigm fromprimarily ambulatory infusion clinics andphysician offices to include self-administrationat home and in assisted living orlong-term care facilities. Such a shift presentsadditional challengesto safe drughandling and administration.11,13 In manyof these settings, oralchemotherapy agentsoften are dispensedor administered withoutproper safeguards.11,14
Yet, consideringthe consequences ofunsafe handling, theOSHA guidelines offerlimited recommendationsregarding thehandling of nonliquidhazardous drugs bypharmacists. Currentrecommendationsstate that tabletsshould be counted ina designated biologicsafety cabinet,which is not availablein the majority ofretail pharmacies;manual countingdevices should notbe used; and automatedcounting machines should beused only if the handler can be isolatedfrom the hazardous drug.12
In settings outside the hospital or infusionclinic, oral chemotherapy may beadministered by patients, family members,or health care personnel withoutoncology experience.11,12 Both OSHA andthe Oncology Nursing Society advise theuse of personal protective equipment(PPE) during administration of chemotherapy.Yet, research evidence on theeffectiveness of PPE against exposure tooral agents is lacking.11,12,15 Equally importantis the fact that individuals in nontraditionalchemotherapy settings may notbe able to comply with OSHA regulationsregarding the use of PPE and the disposalof hazardous waste (eg, gloves, medicinecups) or to readily dispose of anywaste of leftover products with licensedwaste-disposal companies.11Future Directions
Despite awareness of the occupationalrisks for the harmful effects ofchemotherapy drugs for more than 20years, reports continue to documentexposure of health care workers.16Currently, no standardized nationalguidelines exist for the safe handling oforal chemotherapy agents in either traditionalor nontraditional health care settings,and no single institutional policycan serve as an adequate model.
Policies and procedures to reduce riskamong all personnel involved in oralchemotherapy treatment?includingpharmacists?are essential.14,16 Risk-reductionmeasures in nontraditionalsettings should include a 2-person verificationsystem, education of all individualswho will handle and administer oralagents, and procedures for appropriateand secure storage.11
A framework for developing a samplepolicy for safe handling and administrationis suggested in Table 2. This tablewas synthesized from the availablenational and institutional guidelines currentlyavailable in the United States. Bothtraditional and nontraditional facilitieswhere oral chemotherapy is handled anddispensed will need to develop individualizedpolicies and procedures to ensurethe safe handling and administration oforal chemotherapy agents in a variety ofsettings by both skilled and untrainedpersonnel. This framework may serve asa foundation for the development andimplementation of procedures for thesafe handling and administration of oralchemotherapy agents?particularly innontraditional 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.