NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012 DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Institute for Occupational Safety and Health NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012 DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Institute for Occupational Safety and Health This document is in the public domain and may be freely copied or reprinted. Disclaimer Mention of any company or product does not constitute endorsement by the National Institute for Occupational Safety and Health (NIOSH). In addition, citations to Web sites external to NIOSH do not constitute NIOSH endorsement of the sponsoring organizations or their programs or products. Furthermore, NIOSH is not responsible for the content of these Web sites. Ordering Information To receive documents or other information about occupational safety and health topics, contact NIOSH at Telephone: 1–800–CDC–INFO (1–800–232–4636) TTY:1–888–232–6348 E-mail: [email protected] or visit the NIOSH Web site at www.cdc.gov/niosh For a monthly update on news at NIOSH, subscribe to NIOSH eNews by visiting www.cdc.gov/niosh/eNews. DHHS (NIOSH) Publication Number 2012−150 (Supersedes 2010–167) June 2012 Preamble: The National Institute for Occupational Safety and Health (NIOSH) Alert: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings was published in September 2004 (http://www.cdc.gov/niosh/docs/2004-165/). In Appendix A of the Alert, NIOSH identified a sample list of major hazardous drugs. The list was compiled from infor- mation provided by four institutions that have generated lists of hazardous drugs for their respec- tive facilities and by the Pharmaceutical Research and Manufacturers of America (PhRMA) from the American Hospital Formulary Service Drug Information (AHFS DI) monographs [ASHP/ AHFS DI 2003]. The 2004 list was updated in 2010; this update adds 26 drugs to the 2010 list. These additions are new drugs or existing drugs that had new warnings from 2007 to 2009. The review process for the addition of the new listings is described in the Federal Register: http://www.cdc.gov/ niosh/docket/archive/pdfs/NIOSH-190/0190-080211-frn.pdf Appendix A · Drugs Considered Hazardous General Approach to Handling toxic to the patient, some may not pose a risk to health care workers. Hazardous Drugs NIOSH and other organizations are still gath- In the Alert, NIOSH presents a standard pre- ering data on the potential toxicity and health cautions or universal precautions approach effects related to highly potent drugs and bio- to handling hazardous drugs safely: that is, engineered drugs. Therefore, when working NIOSH recommends that all hazardous drugs with any hazardous drug, health care workers be handled as outlined in the Alert. Therefore, should follow a standard precautions approach no attempt has been made to perform drug along with any recommendations included in risk assessments or propose exposure limits. the manufacturer’s MSDSs. The area of new drug development is rapidly evolving as unique approaches are being taken to treat cancer and other serious diseases. ASHP Definition of Hazardous Drugs Defining Hazardous Drugs ASHP defines hazardous drugs in their 1990 revision of Technical Assistance Bulletin on Hazardous drugs include those used for can- Handling Hazardous Drugs [ASHP 1990]. The cer chemotherapy, antiviral drugs, hormones, bulletin gives criteria for identifying poten- some bioengineered drugs, and other miscella- tially hazardous drugs that should be handled neous drugs. The definition of hazardous drugs in accordance with an established safety pro- used in the Alert is based on an ASHP defi- gram [McDiarmid et al. 1991; Arrington and nition that was originally developed in 1990 McDiarmid 1993]. The criteria are prioritized [ASHP 1990]. Thus the definition may not ac- to reflect the hierarchy of potential toxicity de- curately reflect the toxicity criteria associated scribed below. Since the hazardous drugs cov- with the newer generation of pharmaceuticals ered by the Alert were designed as therapeu- entering the health care setting. For example, tic agents for humans, human toxicity profiles bioengineered drugs target specific sites in the should be considered superior to any data from body; and although they may or may not be animal models or in vitro systems. Additional 1 guidance for defining hazardous drugs is avail- Organ toxicity at low doses† able in the following citations: carcinogenic- Genotoxicity‡ ity [61 Fed. Reg. 17960–18011 (1996b); IARC 2010], teratogenicity [56 Fed. Reg. 63798–63826 Structure and toxicity profiles of new drugs (1991)], developmental toxicity [56 Fed. Reg. that mimic existing drugs determined haz- 63798–63826 (1991)], and reproductive toxic- ardous by the above criteria ity [61 Fed. Reg. 56274–56322 (1996a)]. Physi- cal characteristics of the agents (such as liquid versus solid, or water versus lipid solubility) Determining Whether a Drug is also need to be considered in determining the Hazardous potential for occupational exposure. Many hazardous drugs used to treat cancer bind to or damage DNA (for example, alkylat- NIOSH Revision of ASHP Definition ing agents). Other antineoplastic drugs, some antivirals, antibiotics, and bioengineered drugs The 1990 ASHP definition of hazardous drugs* interfere with cell growth or proliferation, or was revised by the NIOSH Working Group on with DNA synthesis. In some cases, the non- Hazardous Drugs for the Alert. Drugs consid- selective actions of these drugs disrupt the ered hazardous include those that exhibit one growth and function of both healthy and dis- or more of the following six characteristics in eased cells, resulting in toxic side effects for humans or animals: treated patients. These nonselective actions can also cause adverse effects in health care Carcinogenicity workers who are inadvertently exposed to haz- Teratogenicity or other developmental ardous drugs. toxicity† Early concerns about occupational exposure to Reproductive toxicity† antineoplastic drugs first appeared in the 1970s. Although the antineoplastic drugs remain the *ASHP [1990] definition of hazardous drugs principal focus of the Alert, other drugs may 1. Genotoxicity (i.e., mutagenicity and clastogenicity also be considered hazardous because they are in short-term test systems) potent (small quantities produce a physiologi- 2. Carcinogenicity in animal models, in the patient population, or both, as reported by the Interna- cal effect) or cause irreversible effects. As the tional Agency for Research on Cancer (IARC) use and number of these potent drugs increase, 3. Teratogenicity or fertility impairment in animal so do opportunities for hazardous exposures studies or in treated patients among health care workers. For example, an- 4. Evidence of serious organ or other toxicity at low doses in animal models or treated patients. †All drugs have toxic side effects, but some exhibit tox- icity at low doses. The level of toxicity reflects a con- al. 2002]. OELs in this range are typically established tinuum from relatively nontoxic to production of toxic for potent or toxic drugs in the pharmaceutical indus- effects in patients at low doses (for example, a few mil- try. Under all circumstances, an evaluation of all avail- ligrams or less). For example, a daily therapeutic dose able data should be conducted to protect health care of 10 mg/day or a dose of 1 mg/kg per day in labora- workers. tory animals that produces serious organ toxicity, de- ‡In evaluating mutagenicity for potentially hazardous velopmental toxicity, or reproductive toxicity has been drugs, responses from multiple test systems are needed used by the pharmaceutical industry to develop occu- before precautions can be required for handling such pational exposure limits (OELs) of less than 10 µg/m3 agents. The EPA evaluations include the type of cells af- after applying appropriate uncertainty factors [Sargent fected and in vitro versus in vivo testing [51 Fed. Reg. and Kirk 1988; Naumann and Sargent 1997; Sargent et 34006–34012 (1986)]. 2 tineoplastic drugs such as cyclophosphamide How to Generate You Own List of have immunosuppressant effects that proved Hazardous Drugs beneficial for treating nonmalignant diseas- es such as rheumatoid arthritis and multiple sclerosis [Baker et al. 1987; Moody et al. 1987; The OSHA hazard communication standard Chabner et al. 1996; Abel 2000]. [29 CFR 1910.1200] requires employers to de- velop a hazard communication program appro- This document presents criteria and sources of priate for their unique workplace. An essential information for determining whether a drug is part of the program is the identification of all hazardous. When a drug has been judged to be hazardous drugs a worker may encounter hazardous, the various precautions outlined in in the facility. Compliance with the OSHA the Alert should be applied when handling that hazard communication standard entails (1) drug. Also included is a list of drugs that should evaluating whether these drugs meet one or be handled as hazardous. This list is based on more of the criteria for defining hazardous a compilation of lists from four health care fa- drugs and (2) posting a list of the hazardous cilities, one drug manufacturers’ organization, drugs to ensure worker safety. Institutions may and NIOSH. wish to compare their lists to the sample listing in this document or on the NIOSH Web site. In addition to using the list of hazardous drugs presented here, each organization should cre- It is not likely that every health care provider ate its own list of drugs considered to be haz- or facility will use all drugs that have received ardous. This document presents guidance for U.S. Food and Drug Administration (FDA) ap- making such a facility-specific list (see section proval, and the OSHA hazard communication entitled How to Generate your own List of Haz- standard does not mandate evaluation of every ardous Drugs). Once this list is made, newly marketed drug.