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, 2014

DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Institute for Occupational Safety and Health

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# Suggested Citation

NIOSH [2014]. 

## NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2014. 

## By Connor TH, MacKenzie BA, DeBord DG, Trout DB, O'Callaghan JP.. Cincinnati, OH: U.S. Department ofHealth and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2014-138 

## (Supersedes 2012-150). 

## DHHS (NIOSH) Publication Number 2014-138 

## (Supersedes 2012-150) 

## September 2014

SAFER • HEALTHIER • PEOPLETM

## 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 information provided by four institutions that had generated lists of hazardous drugs for their respective institutions, as well as a list from the Pharmaceutical Research and Manufacturers of America (PhRMA). The 20041ist was updated in 2010 and 2012. The curreiit update (2014) adds 27 drugs and includes a review of the 20041ist and the consequent removal of 12 drugs that did not meet the NIOSH criteria for hazardous drugs. In addition, a new format has been developed for the list of hazardous drugs, as described below. 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--frn.pdf.


# Appendix A * Drugs Considered Hazardous

In the Alert (NIOSH 2O04) and updates to the hazardous drug list (NIOSH 2O12), NIOSH has recommended standard precautions or universal precautions be taken in handling hazardous drugs. Given the addition of many non-antineoplastic drugs and drugs in tablet and/or capsule form to the list, no single approach can cover the diverse potential occupational exposures to the drugs. The current NIOSH approach involves three groups of drugs:

# ■ Group l: Antineoplastic drugs (AHFS Classification 10:00) [ASHP/AHFS DI 20131. Note thatmany of these drugs may also pose a reproductive risk for susceptible populations (Table 1).

# ■ Group 2: Non-antineoplastic drugs that meetone or more of the NIOSH criteria for a hazardous drug. Note that some of these drugs may also pose a reproductive risk for susceptible populations (Table 2).

# ■ Group 3: Drugs that primarily pose a reproductive risk to men and women who are actively trying to conceive and women who are pregnant or breast feeding, because some of these drugs may be present in breast milk (Table 3).The majority of the reproductive risks associated with the drugs listed in Table 3 are focused on women, but some can apply to men only (such as reduced fertility or sperm count) or to both men and women. Although all hazardous drugs should behandled accordingly, especially if they must be prepared aseptically, some populations of workers may not be at serious risk from handling drugs in Group 3. These include workers who are excluded from the susceptible populations for specific reasons such as age or infertility. In addition, drugs for which the manufacturer includes safe-handling guidance in the package insert are indicated. NIOSH carries out a hazard identification on each drug on the basis of the NIOSH criteria for a hazardous drug.No attempt has been made to perform risk assessments on each drug or to propose exposure limits.NIOSH has provided guidance for personal protective equipment and ventilated engineering controls for some of the various scenarios in which a drug may be handled in health care settings (Table 5). This guidance cannot cover all possible situationsbut provides general recommendations for the major handling events typically seen in health care.

Hazardous drugs include those used for cancer chemotherapy, antiviral drugs, hormoiies, some bioengineered drugs, and other miscellaneous drugs. The deiinition of hazardous drugs used in the Alert is based on a definition originally developed in 1990 by the American Society of Hospital Pharmacists

## [ASHP 1990], currently known as the American

Society of Health-System Pharmacists. Thus, the definition may not accurately reflect the potentialtoxicity criteria associated with some of the newer-generation pharmaceuticals entering the healthcare setting. For example, bioengineered drugs target specific sites in the body, and although they may or may not pose a risk to health care workers, some may pose a risk to patients. NIOSH and other organizations are still gatheringdata on the potential toxicity and health effects related to highly potent drugs and bioengineered drugs. Therefore, when working with any hazardous drug, health care workers should follow the approachesdescribed in Table 5, along with any recommendations included in the manufacturer's Safety Data Sheet (SDS). The 1990 ASHP definition of hazardous drugs' wasrevised by the NIOSH Working Group on Hazardous Drugs for the Alert. Drugs considered hazardous include those that exhibit one or more of the following six characteristics in humans or animals: • Carcinogenicity • Teratogenicity or other developmental toxicityt • Reproductive toxicityt • Organ toxicity at low doses' • Genotoxicity$ • Structure and toxicity profiles of new drugs that nlinlic existing drugs determined hazardous by the above criteria

ASHP defines hazardous drugs in its 1990 revision of the Technical Assistance Bulletin on Handling Hazardous Drugs [ASHP 1990]. The bulletin gives criteria for identifying potentially hazardous drugsthat should be handled in accordance with an established safety program [McDiarmid et al. 1991;Arrington and McDiarmid 1993; ASHP 2006; Massoomi et al. 2008; Eisenberg 2009; ONS 2011]. The criteria are prioritized to reflect the hierarchy ofpotential toxicity described below. Since the hazardous drugs covered by the Alert were designed astherapeutic agents for humans, human toxicity profiles should be considered superior to any data from animal models or in vitro systems. Additional guidance for defining hazardous drugs is available in the following sources: carcinogenicity [61 Fed Regist 17960-18011 (1996b); IARC 2014], teratogenicity[56 Fed Regist 63798-63826 (1991)], developmental toxicity [56 Fed Regist 63798-63826 (1991)], and reproductive toxicity [61 Fed Regist 56274-56322 (1996a)]. Physical characteristics of the agents (such as liquid versus solid or water versus lipid solubility)also need to be considered in determining the potential for occupational exposure. *ASHP [1990] definition of hazardous drugs 1. Genotoxicity (i.e., mutagenicity and clastogenicity in short-term test systems) 2. Carcinogenicity in animal models, in the patient population, or both, as reported by the International Agency for Research on Cancer (IARC) 3. Teratogenicity or fertility impairment in animal studies or in treated patients 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 toxicity atlow doses. 'Ihe level of toxicity reflects a continuum from relatively nontoxic to production of toxic efl'ects in patients atlow doses (for example, a few milligrams or less). For example, a daily therapeutic dose of 10 mg/day or a dose of 1 mg/ kg per day in laboratory animals that produces serious organ toxicity, developmental toxicity, or reproductive toxicity hasbeen used by the pharmaceutical industry to develop occupational exposure limits (OELs) of less than 10 μg/m 3 after applying appropriate uncertainty factors [Sargent and Kirk 1988; Naumann and Sargent 1997; Sargent et al. 2002]. OELs in this range are typically established for potent or toxic drugs in the pharmaceutical industry. Under all circumstances, an evaluation of all available data should be conducted to protect health care workers.#In evaluating mutagenicity for potentially hazardous drugs, responses from multiple test systems are needed before precautions can be required for handling such agents. The EPA evaluations include the type of cells affected and in vitro versus in vivo testing [51 Fed. Regist. 34006-34012 (1986)].

## NIOSH considers it to be highly relevailt. If doses producing an adverse effect are many tinles the MRHD, usually NIOSH does not consider them in its evaluation.Many hazardous drugs used to treat cancer (for example, alkylating agents) bind to or damage DNA. Other antineoplastic drugs, some antivirals, antibiotics, and bioengineered drugs interfere with cell growth or pl

- oliferation, or with DNA synthesis. In some cases, the nonselective actions of these drugs disrupt the growth and function of both healthy and diseased cells, resulting in toxic side effects for treated patients and their offspring. These nonselective actions can also cause adverse effects in health care workers who are inadvertently exposed to hazardous drugs.Early concerns about occupational exposure to antineoplastic drugs first appeared in the 1970s. Although the antineoplastic drugs remain the principal focus of the Alert, other drugs may also be considered hazardous because they are potent (small quantities produce a physiological effect) or cause irreversible effects. As the use and number of these potent drugsincrease, so do opportunities for hazardous exposures among health care workers. For example, antineoplastic drugs such as cyclophosphamide have immunosuppressant effects that proved beneficialfor treating nonmalignant diseases such as rheumatoid arthritis and multiple sclerosis [Baker et a1.1987; Moody et al. 1987; Chabner et al. 1996; Abel 2000].The lack of proper training for handling antineoplastic drugs in other specialty areas may be an issue that needs to be addressed [Polovich and Giesker 2011; Menonna-Quinn et al. 2013].This document presents criteria and sources of information for determining whether a drug is hazardous. When a drug has been judged to be hazardous, the various precautions outlined in the Alert should be applied when handling that drug. Also included is a list of drugs that should be handled ashazardous. When applying the criteria for a hazardous drug as outlined above, NIOSH takes the following approach.
NIOSH takes into account the dose for animaltesting, for reproductive and developmental toxicity, and for carcinogenicity testing. If adverseeffects are observed near, at, or below the maximum recommended human dose (MRHD), • In addition to dose, for carcinogenicity testing NIOSH looks for tumors in more than one species and sex. It looks for tumors in multiple organs andfor tumors that are not rodent-specific. Any available huiilan data are considered significant. • For effects of genotoxicity, NIOSH looks at ifr vivo testing over in vitro testing. However, adverse outcomes in several in vitro tests will be considered in its evaluation. For reproductive and developmental effects, NIOSH notes if there was maternal toxicity, in addition to the dose. Effects on the fetus in theabsence of maternal toxicity are considered relevant. Drugs with an FDA pregnancy category X rating are typically listed as hazardous. Drugs in Category D are often listed as hazardous, but itwill depend on the individual drug. Any available human data are considered significant. • For organ toxicity, the low dose criterion in the definition (a daily therapeutic dose of 10 mg/dayor a dose of 1 mg/kg per day in laboratory animals) is used as a benchmark. • Drugs with safe-handling guidelines from the manufacturer are automatically put on the list because the manufacturer has decided their properties warrant special handling.In addition to using the list of hazardous drugs presented here, each organization should create its ownlist of drugs considered to be hazardous. This document presents guidance for making such a facility-specific list (see section entitled How to Generate Your Own List of Hazardous Drugs). Subsequently, newly purchased drugs should be evaluated againstthe organization's hazardous drug criteria and added to the list if they are deemed hazardous. Organizations have developed various approaches to identifying and classifying hazardous drugs [Chaffee et al. 2010; Badry et al. 2013; Kaestli et al. 2013]. Although the classification schemes may differ somewhat > the drugs listed as hazardous are quite similar.Individual organizations may not have adequate resources for determining their own list of hazardous

## drugs. If so, the list of hazardous drugs in t his document will help employers and workers to determine when precautions are needed. However, reliance on such a published list is a concern because it quickly becomes outdated as new drugs continually enterthe market or listed drugs are removed when additional information becomes available. NIOSH willupdate this list periodically, adding new drugs considered to be hazardous and removing those that require reclassification. This hazardous drug list will be posted on the NIOSH website at www.cdc.gov/ niosh/topics/hazdrug/.

'Ihe OSHA hazard communication standard [29 CFR 1910.1200] requires eniployers to develop a hazard communication program appropriate for their unique workplaces. An essential part of the program is the identification of all hazardous drugs a worker may encounter in the facility. Compliance with the OSHA hazard communication standard entails (1) evaluating whether these drugs meet one or more of the criteria for defining hazardous drugsand (2) posting a list of the hazardous drugs to ensure worker safety. Institutions may wish to compare their lists to the listing in this document or on the NIOSH website.It is not l i kely that every health care provider or facility wi I I use all drugs that have received U.S. Food and Drug Administration (FDA) approval, and the OSHA hazard communication standard does notmandate evaluation of every marketed drug. Instead, compliance requires practice-specific assessments for drugs used at any one time by a facility. However, hazardous drug evaluation is a continual process. Local hazard communication programs should provide for assessment of new drugs as theyenter the marketplace and, when appropriate, reassessment of their presence on hazardous drug lists as toxicological data become available to supportre-categorization. Toxicological data are often incomplete or unavailable for investigational drugs. However, if the mechanism of action suggests that there may be a concern, it is prudent to handle themas hazardous drugs until adequate information becomes available to exclude them. With the increased availability of oral antineoplastic and other hazardous drugs, additional precautions are required in order to prevent worker exposure to these formulations. Some drugs defined as hazardous maynot pose a significant risk of direct occupational exposure because of their dosage formulation (for example, coated tablets or capsules—solid, intact medications that are administered to patients without modifying the formulation). However, they may pose a risk if the formulations are altered, such as by crushing tablets ormaking solutions from them outside a ventilated cabinet [Simmons 2010; Goodin et al. 2011]. Uncoated tablets may present a risk of exposure from dust by skin contact and/or inhalation Nvhen the tablets are counted [Shahsavarani et a1.1993]. All hazardous drugs, regardless of the formulation,should be labeled as such to prevent improper handling. Tablet and capsule forms of hazardous drugsshould not be placed in automated counting machines, which subject them to stress and may introduce powdered contaminants into the work area. Counting and pouring of hazardous drugs should bedone carefully, and clean equipment should be dedicated for use with these drugs. Crushing tablets oropening capsules should be avoided and liquid formulations should be used whenever possible. During the compounding of hazardous drugs (e.g., crushing, dissolving, or preparing a solution or an ointment), workers should wear non-permeable gowns anddouble gloves (Table 5). Guidelines for the safe compounding, administration, and disposal of hazardous drugs have been developed by several organizations [NIOSH 2O04; ASHP 2006; ONS 2011; USP 2014].

Practice-specific lists of hazardous drugs (usually developed by pharmacy or nursing departments) should be comprehensive, including all hazardous medications routinely used or very likely to be used

## by a local practice. Here are some of the resources

that employers can use to evaluate the hazard potential of a drug: • Safety Data Sheets (SDSs, formally Material Safety Data Sheets) • Product labeling approved by the U.S. FDA (drug package inserts) • International Agency for Research on Cancer (IARC) http://www.iarc.fr • Drugbank: http://www.drugbank.ca/• DailyMed: http://dailymed.nlm.nih.gov/dailymed/ • Special health warnings from drug ilianlli

- acturers, FDA, and other professional groups and organizations • Reports and case studies published in medical and other health care profession journals • Evidence-based recommendations fronm otherfacilities that meet the criteria defining hazardous drugs

'Ihe following list (Tables 1-3) contains those drugs that NIOSH has reviewed according to the criteria in the NIOSH definition of a hazardous drug. The list was compiled from the following: • the original list published in 2004 

## (NIOSH 2004), 

## which was a compilation of five lists available to NIOSH at the time (subsequently, the list was re-evaluated against the NIOSH criteria and several drugs were removed; Table 4a) • the 2012 

## NIOSH update to the list • the NIOSH 2O14 update to the list, for which 27drugs were added (including five with manufacturers' safe-handling warnings) and one drug,tetracycline, was deleted on the basis of re-evaluation and feedback from stakeholders (Table 4b).
The OSHA hazard communication standard requires hazardous drugs to be handled with use of special precautions. The mandate applies not only to health care professionals who provide direct patient care but also to others who support patient care byparticipating in product acquisition, storage, transportation, housekeeping, and waste disposal. Institutions may want to adopt this list or compare theirs with the list on the NIOSH website. CAUTION: Drugs purchased and used by a facilitymay have entered the marketplace after the list below was assembled. Therefore, this list may not be all-inclusive. I f you use a drug that is not included in the list of hazardous drugs, check the available literature to see whether the unlisted drug should be treated ashazardous. Check the SDS from the manufacturer or the drug package insert. You lnay also check with other institutions that might be using the samedrug. If any of the documents mention carcinogenicity, genotoxicity, teratogenicity (Section 13 in package insert), or reproductive or developmental toxicity (Section 8), or if the package insert containssafe-handling warnings (Section 16), use the precautions stipulated in the Alert. If the drug meets one or more of the criteria for hazardous drugs in the NIOSH definition, handle it as hazardous.The list of hazardous drugs will be updated periodically on the website, hpp://www.cdc.gov/niosh/topics/hazdrug/. This list supersedes both the 20041ist, http://www. cdc.gov/niosh/docs/2004-165/ and the 2012 list http://www.cdc.gov/niosh/docs/2012-150.

Abel EA [2000]. Immunosuppressant and cytotoxicdrugs: unapproved uses or indications. Clin Dermatol 18:95-101. Arrington DM, McDiarmid MA [1993]. Comprehensive program for handling hazardous drugs. Am J Hosp Pharm 50:1170-1174. ASHP (American Society of Hospital Pharmacists)[1990]. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm 47:1033-1049. ASHP (American Society of Health-System Pharmacists) [2006]. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm 63:1172-1193. ASHP/AHFS DI (American Hospital Formulary Service Drug Information) [2013]. AHFS drug information online updates, www.ahfsdruginformation.com

.

### Baker GL, Kahl LE, Zee BC, Stolzer BL, Agarwal AK,

Medsger TA Jr [1987]. Malignancy following treatment of rheumatoid arthritis with cyclophosphamide. Long-term case-control follow-up study. Am J Med 83(1):1-9. Badry N, Fabbro J, de Lemos ML [2013]. Hazards in determining whether a drug is hazardous. J OncolPharm Pract. doi: 10.1177/1078155213496675 (published online 20 August). CFR. Code of Federal regulations. NNashington, DC: U.S. Government Printing Office, Office of the Federal Register. Chabner BA, Allegra CJ, Curt GA, Calabresi P[1996]. Antineoplastic agents. In: Hardman JG, Limbird LE,eds. Goodman and Gilman's the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, pp. 1233-1287. Chaffee BW, Armistead JA, Benjamin BE, Cotugno MC, Forrey RA, Hintzen BL, Pfeiffenberger T, StevensonJG [2010]. Guidelines for the safe handling of hazardous drugs: consensus recommendations. Am J Health-Syst Pharm 67:1545-1546. Eisenberg S[2009]. Safe handling and administration of antineoplastic chemotherapy. J Infus Nurs 32(1):23- 32. Goodin S, Griffith N, Chen B, Chuk K, Daouphars M, Doreau C, 1'atel RA, Schwartz R, Tames MJ, TerkolaR, Vadnais B, Wright D, Meier K[2011]. Safe handling of oral chemotherapeutic agents in clinical practice: recommendations from an international pharmacy panel. J Oncol Pract 7(1):7-8. IARC [2014]. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Lyon, France: World Health Organization, International Agency for Research on Cancer. www. iarc.fr . Date accessed: March 2014. Kaestli L-Z, Fonzo-Christe C, Bonfillon C, Desmueles J, Bonnabry P[2013]. Development of a standardizedmethod to recommend protective measures to handle hazardous drugs in hospitals. Eur J Hosp Pharm 20:100-105.Massoomi F, Neff B, Rick A, Denekas P[2008]. Implementation of a safety program for handling hazardous drugs in a community hospital. Am J Heath-Sys Pharm 65:861-865.McDiarmid MA, Gurley HT, Arrington D[1991]. Pharmaceuticals as hospital hazards: managing the risks. J Occup Med 33(2):155-158.Menonna-Quinn D[2013]. Safe handling of chemotherapeutic agents in the treatment of nonmalignant diseases. J Infus Nurs 36(3):198-204. Moody DJ, Kagan J, Liao D, Ellison GW, Myers LW[1987]. Administration of monthly-pulse cyclophosphamide in multiple sclerosis patients. Effects of long-term treatment on immunologic parameters. J Neuroimmuno114(2):161-173.Naumann BD, Sargent EV [1997]. Setting occupational exposure limits for pharmaceuticals. Occup Med: State of the Art Rev 12(1):67-80.NIOSH [2004]. NIOSH alert: preventing occupational exposure to antineoplastic and other hazardous drugs in health care settings. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165. NIOSH [2012]. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2012-150 (September). http:// nioshdev.cdc.gov/niosh/docs/2012-150. ONS (Oncology Nursing Society) [2011]. Safe handlingof hazardous drugs. 2nd Ed. M. Polovich, ed. Pittsburgh, PA: Oncology Nursing Society. Polovich M, Giesker KE [2011]. Occupational hazardous drug exposure among non-oncology nurses. Medsurg Nurs 20(2):79-85,97. Sargent EV, Kirk GD [19881. Establishing aii

- borne exposure control limits in the pharmaceutical industry. Am Ind Hyg Assoc J 49(6):309-313.Sargent EV, Naumann BD, Dolan DG, Faria EC, Schulman L[2002]. The importance of huilian data in the establishment of occupational exposure limits. Hum Ecol Risk Assess 8(4):805-822.Shahsavarani S, Godefroid RJ, Harrison BR [1993]. Evaluation of occupational exposure to tablet trituration dust [abstract]. ASHP Midyear Clinical Meeting. Document No. P-59(E).Simmons CC [2010]. Oral chemotherapeutic drugs: handle with care. Nursing 40(7):44-47.U.S. Pharmacopeia (USP) [2014]. Pharmaceutical Compounding: Sterile Preparations. Revised chapter 797 (USP 37-NF 32).



## This document was written by 'Ihomas H. Connor, PhD; Barbara A. MacKenzie, BS; D. Gayle DeBord, PhD; Douglas B. Trout, MD, MHS; and James P. O'Callaghan, PhD, all of NIOSH. Seleen Collins provided editorial services. RyanDufour, Nicole Romero, and Vanessa Williams provided graphic design and production services.

# NIOSH List of Antineoplastic and Other Hazardous Drugs

in Healthcare Settings 2014
NIOSH performs a hazard identification on each of the drugs in the following tables. The actual risk to health care workers depends on what is done with the drugs—how they are manipulated, how oftenthey are handled, and what type of engineering controls and personal protective equipment (PPE) are used (see Table 5). For example, • Dispensing a single tablet to a patient poses little to no risk to the healthcare worker. A single pair of gloves would be adequate.• Repeatedly counting, cutting, or crushing tablets may pose a higher risk of worker exposure and contamination to the workplace if proper precautions are not in place. If a containment device such as a BSC (Class II biological safetycabinet) or CACI (compounding aseptic containment isolator) is not available, then doublegloves, a protective gown, respiratory protection, and a disposable pad to protect the work surface should be used. Preparing a number of intravenous doses of anantineoplastic drug typically poses a higher potential risk to the worker. In addition to double gloving and a protective gown, an engineeringcontrol such as a BSC or CACI, possibly supplemented with a CSTD (closed system drug transfer device), is required to protect the drug, environment, and health care worker.

### The drugs in Table 1 meet one or more of the NIOSH criteria for a hazardous drug. These drugs represent an

occupational hazard to health care workers and should always be handled ivith use of reconimended engineering controls and personal protective equipment (PPE), regardless of their formulation (IV [intravenous], SC [subcutaneous], topical, tablet, or capsule). Unopened, intact tablets and capsules may not pose the samedegree of occupational exposure risk as injectable drugs, which usually require extensive preparation. Cutting, crushing or otherwise manipulating tablets and capsules will increase the risk of exposure to workers. In addition to many of these drugs being cytotoxic, the niajority are hazardous to males or females who areactively trying to conceive, women who are pregnant or may become pregnant, or women who are breast feeding, because they may be present in breast milk. Manufacturers' safe-handling guidance (MSHG) is typically in Sectioii 16 of the drug package insert. See Table 5 for safe-handling recommendations. AHFS = American Hospital Formulary Service; MHRD = maximum recommended human dose. 'Drugs in red font were added in 2014. "International Agency for Research on Cancei - (www.iarc.fr ). "'BCG, although classified as a vaccine, is used in the treatment of certain cancers. BCG should be prepared with aseptic techniques. To avoid cross-contamination, parenteral drugs should not be prepared in areas where BCG has been prepared. A separate area for the preparation of BCG suspension is reconiinended. All equipmeiit, supplies, and receptacles in contact with BCG should be liandled and disposed of as biohazardous. If preparation cannot be performed in a containment device, then respiratory protection, gloves, and a gown should be woi

- n to avoid inhalation or contact with BCG organisms.



### Table 1. Antineoplastic drugs including those with manufacturers" safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

abiraterone* 10:00 antineoplastic agents

ado- 10:00 antineoplastic agents yes trastuzumab emtansine

altretamine 10:00 antineoplastic agents yes

amsacrine NA antineoplastic agents yes

anastrozole 10:00 antineoplastic agents

arsenic trioxide 10:00 antineoplastic agents yes

azacitidine 10:00 antineoplastic agents yes

bacillus 80:12 vaccines yes calmette Guerin (BCG)***

bendamustine 10:00 antineoplastic agents yes

bexarotene 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed; DrugBank
Conjugated monoclonal DailyMed; DrugBank antibody; FDA Pregnancy Category D
FDA Pregnancy category D DailyMed; DrugBank
IARC Group 2B DrugBank
FDA Pregnancy category X DailyMed; DrugBank
IARC Group 1 carcinogen**; DailyMed; DrugBank FDA Pregnancy Category D
IARC Group 2A carcinogen; DailyMed; DrugBank FDA Pregnancy Category D
See special handling DailyMedrequirements**; FDA Pregnancy Category C
FDA Pregnancy Category D DailyMed;
FDA Pregnancy Category X DailyMed; DrugBank



### (continued)

8

### Table 1(Contintued). Antineoplastic drugs including those with manufacturers' safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

bicalutimide 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed; DrugBank
bleomycin 10:00 antineoplastic agents yes IARC Group 213; FDA Preg- DailyMed; DrugBank nancy Category D

bortezomib 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

brentuximab 10:00 antineoplastic agents yes Conjugated monoclonal DailyMed; DrugBank vedotin antibody; FDA Pregnancy Category D

busulfan 10:00 antineoplastic agents yes IARC Group 1 carcinogen; DailyMed; DrugBank FDA Pregnancy Category D

cabazitaxel 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank
capecitabine 10:00 antineoplastic agents yes Metabolized to 5-fluoro- DailyMed; DrugBankuracil; FDA Pregnancy Category D
carboplatin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

carmustine 10:00 antineoplastic agents yes IARC Group 2A carcinogen; DailyMed; DrugBank FDA Pregnancy Category D

chlorambucil 10:00 antineoplastic agents yes IARC Group 1 carcinogen; DailyMed; DrugBank FDA Pregnancy Category D
cisplatin 10:00 antineoplastic agents yes IARC Group 2A carcinogen; DailyMed; DrugBank FDA Pregnancy Category D

cladribine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

clofarabine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

crizotinib 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed
cyclophospha- 10:00 antineoplastic agents yes IARC Group 1 carcinogen; DailyMed; Drugbank mide FDA Pregnancy Category D
cytarabine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

dacarbazine 10:00 antineoplastic agents yes FDA Pregnancy Category C DailyMed; Drugbank
dactinomycin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

dasatinib 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; Drugbank

daunorubicin 10:00 antineoplastic agents yes IARC Group 213, AKA dauno- DailyMed; Drugbankmycin; FDA Pregnancy Category D (continued)

9

### Table 1(Contintued). Antineoplastic drugs including those with manufacturers' safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

decitabine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; Drugbank
degarelix 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed; Drugbank

docetaxel 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

doxorubicin 10:00 antineoplastic agents yes IARC Group 2A carcinogen; DailyMed; DrugBank FDA Pregnancy Category D
epirubicin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; Drugbank

eribulin 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

erlotinib 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

estramustine 10:00 antineoplastic agents yes FDA Pregnancy Category X DailyMed; Drugbank
etoposide 10:00 antineoplastic agents yes IARC Group 1 carcinogen; DailyMed; DrugBank FDA Pregnancy Category D

everolimus 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; Drugbank

exemestane 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed; DrugBank

floxuridine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

fludarabine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

fluorouracil 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

flutamide 10:00 antineoplastic agents Indicated only for men; FDA DailyMed; DrugBank Pregnancy Category D

fulvestrant 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank
gemcitabine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank
gemtuzumab 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank ozogamicin
goserelin 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed; Drugbank
hydroxyurea 10:00 antineoplastic agents yes Special warning on handling DailyMed; DrugBank bottles and capsules FDA Pregnancy Category D

idarubicin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

ifosfamide 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

(continued)

10

### Table 1(Contintued). Antineoplastic drugs including those with manufacturers' safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

imatinib 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

irinotecan 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank
ixabepilone 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

letrozole 10:00 antineoplastic agents FDA pregnancy Category X DailyMed; DrugBank
leuprolide 10:00 antineoplastic agents yes FDA Pregnancy Category X DailyMed; Drugbank

lomustine 10:00 antineoplastic agents yes IARC Group 2A carcinogen; DailyMed; DrugBank FDA Pregnancy Category D

mechlorethamine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

megestrol 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed; DrugBank
melphalan 10:00 antineoplastic agents yes IARC Group 1 carcinogen; DailyMed; DrugBank FDA Pregnancy Category D
mercaptopurine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

methotrexate 10:00 antineoplastic agents yes FDA Pregnancy Category X DailyMed; DrugBank
mitomycin 10:00 antineoplastic agents yes IARC Group 2B; FDA Preg- DailyMed; DrugBank nancy Category D

mitotane 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

mitoxantrone 10:00 antineoplastic agents yes IARC Group 2B; FDA Preg- DailyMed; DrugBank nancy Category D

nelarabine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

nilotinib 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

omacetaxin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank
oxaliplatin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank
paclitaxel 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank
pazopanib 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank
pemetrexed 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank
pentostatin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank
pralatrexate 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank
(continued)



## m

### Table 1(Contintued). Antineoplastic drugs including those with manufacturers' safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links
procarbazine 10:00 antineoplastic agents yes IARC Group 2A carcinogen; DailyMed; DrugBank FDA Pregnancy Category D
romidepsin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed

sorafenib 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank
streptozocin 10:00 antineoplastic agents yes IARC Group 213; FDA Preg- DailyMed; DrugBank nancy Category D

sunitinib 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

tamoxifen 10:00 antineoplastic agents IARC Group 1 carcinogen; DailyMed; DrugBank FDA Pregnancy Category D

temozolomide 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

temsirolimus 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank teniposide 10:00 antineoplastic agents yes IARC Group 2A carcinogen; DailyMed; DrugBank FDA Pregnancy Category D
thioguanine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank thiotepa 10:00 antineoplastic agents yes IARC Group 1 carcinogen; DailyMed; DrugBank FDA Pregnancy Category D
topotecan 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

toremifene 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

trimetrexate 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank triptorelin 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed

valrubicin 10:00 antineoplastic agents yes FDA Pregnancy Category C DailyMed; DrugBank

vandetanib 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

vemurafenib 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

vinblastine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

vincristine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; Drugbank

vinorelbine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

vorinostat 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; Drugbank

12

### The drugs in Table 2 meet one or more of the NIOSH criteria for a hazardous drug. Unopened, intact tablets

and capsules may not pose the same degree of occupational exposure risk as injectable drugs, which usually require extensive preparation. Cutting, crushing, or otherwise manipulating tablets and capsules will increase the risk of exposure to workers. Some of these drugs may represent an occupational hazard to males or females who are actively trying to conceive, women wllo are pregnant or may become pregnant, or wonien who are breast feeding, because they may be present in breast milk. Manufacturers' safe-handling guidance (MSHG) is typically in Section 16 of the drug package insert. See Table S for safe-handling recommendations. AHFS = American Hospital Formulary Service; MHRD = maximum recommended human dose. 'Drugs in red font were added in 2014. "International Agency for Research on Cancer, www.iarc.fr"'Drugs in blue font meet one or more additional criteria for a hazardous drug and also pose a potential reproductive hazard.



### Table 2. Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug including those with manufacturers' safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

abacavir' 8:18.08.20 nucleoside and FDA Pregnancy Category C; DailyMed; DrugBank

reverse transcriptase malignant tumors observed inhibitors in male and female mice arid rats; genotoxic in in vivo micronucleus test.

alefacept 84:92 skin and mucous

membrane agents, miscellaneous

apomorphine 28:36.20.08 Nonergotderivative dopamine receptor agonists

azathioprine 92:44 immunosuppressant yes

agents
carbamazepine 28:12:92 anticonvulsants,

miscellaneous Increased frequency of DailyMed; DrugBank malignancies observed intreated patients; FDA Pregnancy Category B
FDA Pregnancy Category C; DailyMed; DrugBank genotoxic in several in vitro assays.
IARC Group 1 carcinogen**; DailyMed; DrugBank FDA Pregnancy Category D***
Black Box warning for DailyMed; Drugbank aplastic anemia; congenital malformations in offspring of mothers who took drug; rapid transplacental passage; FDA Pregnancy Category D

(continued)

13

## Table 2(Contintued). Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug including those with manufacturers' safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

chloramphenicol 8:12:08 chloramphenicols IARC Group 2A carcinogen; DailyMed; DrugBank FDA Pregnancy Category C

cidofovir 8:18:32 nucleoside and yes FDA Pregnancy Category C DailyMed; Drugbank

nucleotides

cyclosporine 92:44 immunosuppressive IARC Group 1 carcinogen; DailyMed; Drugbank

agents FDA pregnancy Category C
deferiprone 64:00 Heavy metal Genotoxic in vitro and in vivo; DailyMed; DrugBank

antagonists FDA Pregnancy Category D

dexrazoxane 92:56 protective agents yes FDA Pregnancy Category C; DailyMed; DrugBank secondary malignancies observed in patients treated long term with Razoxane (a racemic mixture containing dexrazane); genotoxic in vitro and in vivo; in laboratory studies, testicular atrophy observed at or below the human dose
diethylstilbestrol NA IARC Group 1 carcinogen; DrugBank FDA Pregnancy Category X
divalproex 28:12:92 anticonvulsants, Black Box warning for tera- DailyMed

miscellaneous togenicity; FDA Pregnancy Category D; tumors seen in laboratory studies at doses below MRHD

enticavir 8:18:32 nucleosides and yes FDA Pregnancy Category C DailyMed; DrugBank

nucleotides

(continued)

14

## Table 2(Continued). Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug including those with manufacturers' safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

estradiol 68:16:04 estrogens Black Box warning for malig- DailyMed; DrugBank nant neoplasms; increased risk of endometrial cancer, breast cancer, and ovarian cancer; in laboratory studies,increased frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver; present in breast milk; FDA Pregnancy Category X
estrogen/ 68:12 contraceptives IARC Group 1 carcinogen; DailyMed progesterone FDA Pregnancy Category X combinations

estrogens, 68:16:04 estrogens Black Box warning for endo- DailyMed conjugated metrial cancer and cardiovascular risks; long-term use in women and laboratory studies increases frequencyof several cancers; FDA Pregnancy Category X

estrogens, 68:16:04 estrogens esterified

estropipate 68:16:04 estrogens

fingolimod 92:20 biologic response

modifiers Black Box warning for DailyMedendometrial cancer and cardiovascular risks: FDA Pregnancy Category X

Black Box warning for endo- DailyMed; DrugBankmetrial carcinoma in postmenopausal women and use during pregnancy; FDA Pregnancy Category X
FDA Pregnancy Category DailyMed; DrugBank C; in laboratory studies, increased malformations and embryo-fetal deaths at less than the RHD; malignant lymphomas observed in male and female mice.

(continued)

15

## Table 2(Continued). Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug including those with manufacturers' safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

fluoxymesterone 68:08 androgens Tumors in mice and rats and DailyMed; DrugBankpossibly humans; FDA Pregnancy Category X

fosphenytoin 28:12.12 hydantoins Metabolized to phenytoin; DailyMed; DrugBank FDA Pregnancy Category D
ganciclovir 8:18:32 nucleosides and yes FDA Pregnancy Category C DailyMed; DrugBank

nucleotides

leflunomide 92:36 disease-modifying Teratogenic in laboratory DailyMed; DrugBank

antirheumatic agents studies at 1/10 HD; marked postnatal survival at 1/100HD; FDA Pregnancy Category X; severe liver injuryreported in patients; carcinogenicity observed at doses below HD

lenalidomide 92:20 biologic response yes Analog of thalidomide; FDA DailyMed; DrugBank

modulators Black box warnings for limbabnormalaties; pregnancy Category X; in laboratory studies, caused thalidomide-type limb defects in monkey offspring
liraglutide 68:20.06 incretin mimetics FDA Pregnancy Category C; DailyMed; DrugBank recombinant Black Box warning for thyroid C-cell tumors, withsupporting evidence in laboratory studies; also in laboratory studies, teratogenic at or below the MRHD.
medroxyproges- 68:32 progestins yes IARC Group 2B; FDA Preg- DailyMed; DrugBank terone acetate nancy Category X

(continued)

16

## Table 2(Continued). Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug including those with manufacturers' safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

mycophenolate 92:44 immunosuppressive Black Box warning for DailyMed; DrugBankmofetil agents embryo fetal toxicity, malignancies and serious infections; Increased risk of firsttrimester pregnancy loss and increased risk of congenitalmalformations; FDA Pregnancy Category D; Special warning: tablets should not be crushed and capsules should not be opened or crushed. Avoid inhalation or direct contact with skin or mucous membranes of the powder contained in capsules and oral suspension (before or after constitution). If such contact occurs, wash thoroughly with soap and water; rinse eyes with plain water.
mycophenolic 92:44 immunosuppressive Black Box warning for first DailyMed; DrugBank acid agents trimester pregnancy lossand an increased risk of congenital malformations; FDA Pregnancy Category D; Black Box warning for lymphomas and other malignancies; genotoxic in vitro and in vivo
nevirapine 8:18.08.16 nonnucleoside FDA Pregnancy Category B; DailyMed; DrugBank

reverse transcriptase in laboratory studies, hepainhibitors tocellular adenomas and carcinomas at doses lower than human dose.

oxcarbazepine 28:12:92 anticonvulsants, Tumors observed in labora- DailyMed; Drugbank

miscellaneous tory studies at 1/10 MRHD; FDA Pregnancy Category C

(continued)

17

## Table 2(Continued). Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug including those with manufacturers' safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

palifermin 84:16 cell stimulants and

proliferants

phenoxyben- 12:16:04:04 non-selective zamine alpha-andrenergic blocking

agents
phenytoin 28:12.12 hydantoins

pipobroman NA

progesterone 68:32 progestins

progestins 68:12 contraceptives

propylthiouracil 68:36.08 antithyroid agents

raloxifene 68:16:12 estrogen agonists-antagonists

rasagiline 28:36 antiparkinsonian

agents
risperidone 28:16:08:04 atypical antipsychotics

sirolimus 92:44 immunosuppressive

agents FDA Pregnancy Category C; DailyMed; Drugbank potential for stimulation of tumor growth
IARC Group 2B; FDA Preg- DailyMed; DrugBank nancy Category C

IARC 2B; FDA Pregnancy Cat- DailyMed; DrugBank egory D
FDA Pregnancy Category D Drugbank

IARC Group 2B DailyMed; Drugbank

FDA Pregnancy Category X

IARC 2B; FDA Pregnancy Cat- DailyMed; DrugBank egory D
Abortion and developmental DailyMed; Drugbank abnormalities seen at low doses in laboratory studies; evidence of tumors at low doses in laboratory studies; FDA Pregnancy Category X
FDA Pregnancy Category C DailyMed; Drugbank

Evidence of tumors at low DailyMed; DrugBank doses in laboratory studies; may be prolactin-mediated; FDA Pregnancy Category C
AKA rapamycin; increased DailyMed; DrugBank risk of lymphomas and other malignancies; embryotoxic and fetotoxic at 0.2 HD; FDA Pregnancy Category C

(continued)

18

## Table 2(Continued). Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug including those with manufacturers' safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

spironolactone 24:32.20 mineralocorticoid FDA Pregnancy Category C; DailyMed; DrugBank

receptor antagonists black box warning for tumorogenicity in laboratory studies.

tacrolimus 92:44 immunosuppressive Increased risk of lymphomas DailyMed; DrugBank

agents and other malignancies; reproductive effects seen in laboratory studies below the MRHD; excreted in breastmilk; FDA Pregnancy Category C

thalidomide 92:20 biologic response yes FDA Pregnancy Category X DailyMed; DrugBank

modulators

uracil mustard NA yes FDA Pregnancy Category D DrugBank

valganciclovir 8:18:32 nucleosides and yes FDA Pregnancy Category C DailyMed; DrugBank

nucleotides

zidovudine 8:18:08 antiretroviral agents IARC Group 213; FDA Preg- DailyMed; DrugBank nancy Category C

19

### The drugs in Table 3 primarily meet the NIOSH criteria for reproductive hazards. They represent a potential

occupational hazard to males or females who are actively trying to conceive, women who are pregnant or may become pregnant, or breast feeding as they may be present in breast milk. Unopened, intact tablets and capsules may not pose the same degree of occupational risk as injectable drugs that usually require extensivepreparation. Cutting, crushing or otherwise manipulating tablets and capsules will increase the risk of exposure to workers. Manufacturers' safe handling guidance (MSHG) is typically in Section 16 of the drug package insert. See Table S for safe handling recommendations. 'Drugs in red font were added in 2014.



## Table 3. Non-antineoplastic drugs that primarily have adverse reproductive effects

Drug AHFS classification Reason for listing Links

acitretin 88:04 vitamin A Black Box warning on adverse DailyMed; DrugBank reproductive effects; FDA Pregnancy Category X

alitretinoin 84:92 skin and mucous FDA Pregnancy Category D DailyMed; DrugBankmembrane agents, miscellaneous

ambrisentan 24:12:92 vasodilating agents, Black Box warning on adverse DailyMed; miscellaneous reproductive effects; reduced sperm counts in patients; FDA Pregnancy Category X

bosentan 24:12:92 vasodilating agents, Black Box warning on adverse DailyMed; DrugBank miscellaneous reproductive effects; FDA Pregnancy Category X
cabergoline 28:36:20:04 ergot-derivative Inhibition of conception and DailyMed; DrugBank dopamine receptor agonists embryo fetal effects at doses below recommended humandose; FDA Pregnancy Category B

cetrorelix 92:40 gonadotropin- FDA Pregnancy Category X DailyMed; DrugBankreleasing hormone anagonists
choriogonado- 68:18 gonadotropins FDA pregnancy Category C; DailyMed; DrugBank tropin may cause fetal harm when administered to a pregnant
woman.



### (continued)

20

## Table 3(Continued). Non-antineoplastic drugs that primarily have adverse reproductive effects

Increased risk of congenital DailyMed; DrugBank abnormalities when taken in first trimester; FDA Pregnancy Category D
FDA Pregnancy Category C; DailyMed; DrugBankpublished animal reproduction and development studies indicate it causes embryofetal toxicity, teratogenicity, andaltered postnatal development at exposures within or above the clinical therapeutic range
Hazardous only for women DailyMed; DrugBankin late pregnancy; FDA Pregnancy Category C
Teratogenic in laboratory DailyMed; DrugBankstudies at'/z MRHD; FDA Pregnancy Category X

Women warned not to DailyMed; DrugBankhandle; FDA Pregnancy Category X
Use is contraindicated during DailyMed; DrugBank; pregnancy because of its DrugBankuterotonic effects; FDA Pregnancy Category C

Women shoutd not handle DailyMed; Drugbank crushed or broken finasteridetablets when they are pregnant or may potentially be pregnant due to potentia)risk to a male fetus; FDA Pregnancy Category X Drug AHFS classification Reason for listing Links

clonazepam 28:12:08 benzodiapines

colchicine 92:16 antigout agents

dinoprostone 76:00 oxytocics

dronedarone 24:04:04 antiarrythmics

dutasteride 92:08 S-alpha reductase inhibitors

ergonovine/meth- 76:00 oxytocics ylergonovine

finasteride 92:08 S-alpha reductase inhibitors

(continued)

21

## Table 3(Continued). Non-antineoplastic drugs that primarily have adverse reproductive effects

Drug AHFS classification Reason for listing Links

fluconazole 8:18.08 azoles FDA Pregnancy Category C; DailyMed; DrugBankcase reports describe congenital anomalies in infants exposed in utero to maternal fluconazole (400-800 mg/ day) during most or all of the first trimester, similar to those seen in animal studies
FDA Pregnancy Category X DailyMed

68:18 gonadotropins Defects of forelimbs and DailyMed; DrugBank7 central nervous system and alterations in sex ratio have been reported in laboratorystudies; FDA pregnancy Category C
92:32 complement inhibitors FDA Pregnancy Category C; DailyMed; DrugBankin laboratory studies, premature birth and abortion rates increased at a dose that was less than 1/40th the MRHD and delayed parturition and fetal death occurred at 0.5 and 2-fold, respectively, the MRHD
68:18 gonadotropins FDA Pregnancy Category X Drugbank
68:08 androgens FDA Pregnancy Category X DailyMed; DrugBank

76:00 oxytocics When given to pregnant DailyMed; DrugBank women results in termination of pregnancy; FDA Pregnancy Category X
misoprostol 56:28.28 prostaglandins FDA Pregnancy Category X DailyMed; DrugBank ganirelix 92:40 gonadotropineleasing hormone antagonists
gonadotropin, chorionic

icatibant

mentropins
methyltestosterone
mifepristone

(continued)

22

## Table 3(Continued). Non-antineoplastic drugs that primarily have adverse reproductive effects

Drug AHFS classification Reason for listing Links

nafarelin 68:18 gonadotropins Note: Given only as nasal DailyMed; DrugBankspray; no potential for occupational exposure; FDA Pregnancy Category X

oxytocin 76:00 oxytocics Hazardous only for women in DailyMed; DrugBank 3rd trimester; FDA Pregnancy Category C

paroxetine 28:16:04:20 selective sero- Increased risk of congenital DailyMed; Drugbank tonin uptake inhibitors abnormalities when taken in first trimester; complications in pregnancy when taken inthird trimester; FDA Pregnancy Category D

pentetate calcium NA Severe teratogenic effects in DailyMed trisodium laboratory studies in dogs: supplied in ampule which can lead to occupational exposure; FDA Pregnancy Category C

plerixafor 20:16 hematopoietic agents Teratogenic in laboratory DailyMed; DrugBankstudies; FDA Pregnancy Category D

ribavirin 8:18:32 nucleosides and Teratogenic and embryotoxic DailyMed; DrugBank nucleotides effects in several laboratory studies; contraindicated in women who are pregnant and in the male partners of women who are pregnant; FDA Pregnancy Category X

telavancin 8:12:28 glycopeptides Black Box warning for poten- DailyMed; Drugbank tial risk to fetus and adverse reproductive outcomes; reduced fetal weights and increased rates of digit and limb malformations in three species at clinical doses; FDA Pregnancy Category C

(continued)

23

## Table 3(Continued). Non-antineoplastic drugs that primarily have adverse reproductive effects`

Drug AHFS classification Reason for listing Links

testosterone 68:08 androgens Children should avoid contact DailyMed; DrugBank with unwashed or unclothed application sites on skin; FDA Pregnancy Category X

topiramate 28:12.92 anticonvulsants, FDA Pregnancy Category D DailyMed; DrugBank miscellaneous

tretinoin 84:16 cell stimulants and Black Box warning for severe DailyMed; DrugBank proliferants birth defects; Special FDA distribution system; FDA Pregnancy Category X

ulipristal 68:12 contraceptives FDA Pregnancy Category X DailyMed
valproate/valproic 28:12:92 anticonvulsants, Black Box warning for terato- DailyMed; DailyMed; acid miscellaneous genicity; congenital malfor- DrugBank mations including neural tubedefects and others; teratogenic in multiple species; FDA Pregnancy Category D

vigabatrin 28:12:92 anticonvulsants, Malformations seen in labora- DailyMed; Drugbank miscellaneous tory studies below the MRHD; FDA Pregnancy Category C

voriconazole 8:14.08 azoles FDA Pregnancy Category D DailyMed; DrugBank

warfarin 20:12.04.08 coumarin FDA Pregnancy Category D DailyMed; DrugBank derivatives

ziprasidone 28:16:08:04 atypical Developmental toxicity, DailyMed; Drugbank antipsychotics including possible teratogenic effects at doses similar to human therapeutic doses; an increase in the number of pups born dead and a decrease in postnatal survivalat less than MRHD; FDA Pregnancy Category C

(continued)

24

### Table 3(Continued). Non-antineoplastic drugs that primarily have adverse reproductive effects'

Drug AHFS classification Reason for listing Links

zoledronic acid 92:24 bone resorption Number of stillbirths DailyMed; DrugRank inhibitors increased and survival of neonates decreased in laboratory studies at low doses; FDA Pregnancy Category D

zonisamide 28:12:92 anticonvulsants, Teratogenic in multiple DailyMed; Drug[3ank miscellaneous animal species; FDA Pregnancy Category C

25

### Table 4lists drugs that were deleted from the 2004 and 2012 NIOSH hazardous drug lists. The 20041ist was

a composite of five separate lists. When the drugs on that list were reviewed against the NIOSH criteria for hazardous drugs, these 11 drugs did not meet the criteria. Tetracycline was removed from the 2012 list on the basis of feedback from stakeholders. *AHFS = American Hospital Formulary Service.



### Table 4a. Drugs deleted from the 2004 hazardous drug list for not

meeting the NIOSH criteria for hazardous drugs

Drug AHFS Classification'

aldesleukin 10:00 antineoplastic agents
asparaginase 10:00 antineoplastic agents

denileukin 10:00 antineoplastic agents

estrone 68:16.04 estrogens

nilutamide 10:00 antineoplastic agents

pegaspargase 10:00 antineoplastic agents
pentamidine isethionate 8:40 miscellaneous anti-infectives
podofilox/podophyllum resin 84:36 miscellaneous skin and mucous membrane agents (mitotic inhibitor)

testolactone 10:00 antineoplastic agents

trifluridine 52:04.06 antivirals

vidarabine 52:04.06 antivirals



### Table 4b. Drugs deleted from the 2012 list on the basis of stakeholder comments

Drug AHFS Classification*
Tetracycline 8:12.24 tetracyclines

26no no N/A

no yes, if not done yest

in a control device

noz yes, if powder N/A

generated

yes, if not yes, if not done yest done in in a control a control device device

no# no$ N/A

yes yes, if not done yest

in a control device
yes, if liquid yes, if inhalation N/A that could potential splash#
yes, if not yes, if not done yes, BSC or done in in a control CACI a control device device 

### Table S provides general guidance for some of the possible scenarios that may be encountered in health care settings where hazardous drugs are handled, but it cannot cover all possible situations. 'Ihis guidance applies to the drugs in Tables 1-3. For more detailed information on safe-handling practices, see the reference list [NIOSH 2O04; ASHP 2006; USP 2008; ONS 2011].



## Table 5. Personal protective equipment and engineering controls for working with hazardous drugs in healthcare settings'

Ventilated

Double Protective Eye Respiratory engineering Formulation Activity gloves gown protection protection controls

Intact tablet or Administration no (single no capsule from unit-dose glove

package should be

used)

Tablets or cap- Cutting, yes yes sules crushing or

otherwise manipulatingtablets or capsules

Administration yes yes

Oralliquid Compounding yes yes drug

Administration yes yes
Topical drug Compounding yes yes

Administration yes yes

Ampoule Opening yes yes

(continued)

27

### Table 5(Continued). Personal protective equipment and engineering controls for working with hazardous drugs in healthcare settings"

Formulation Activity Double gloves Protective

gown Eye

protection Respiratory

protection Ventilated

engineering controls
Subcutaneous, Preparation yes yes yes, if not yes, if not done yes, BSC or intramuscular (withdrawing done in in a control CACI injection from vial or a control device

ampoule) device

Administration yes yes yes, if liquid yes, if inhalation N/A from prepared that could potentiali syringe splash'

Intravenous Compounding yes yes yes, if not yes, if not done yes, BSC or solution done in in a control CACI; recoma control device mend use of device CSTD

Administration yes yes yes, if liquid yes, if inhalation N/A; recomof prepared that could potential= mend use of solution` splasht CSTD

Solution for Compounding yes yes yes, if not yes, if not done yes, BSC or irrigation done in in a control CACI; recoma control device mend use of device CSTD

Administration yes yes yes yes N/A (bladder, HIPEC, limb perfusion, etc.)

Powder/ Inhalation yes yes yes yes yes, when solution for applicable inhalation

*The table provides general guidance for some of the possible scenarios that may be encountered in healthcare settings, but cannot cover all possible situations. For more detailed information on safe handling practices, see the reference list [NIOSI I 2004; ASHP 2006; USP 2008, and ONS 2011 ]. 13SC= Class II biological safety cabinet; CACI = compounding aseptic containment isolator; CS'I'D = closed system drug transfer device; HIPF,C = hyperthermic intraperitoneal chemotherapy ~ 'For nonsterile preparations, an engineering control such as a fume hood or Class I BSC is sufficient. It is recommended that these activities be carried out in a control device, but it is recognired that under so ne circumstances, it is not possible. If the activity is perfor ned in an engineering control that is used for sterile intravenous preparations, a thorough cleaning is required following the activity. *Required if patient may resist (infant, unruly patient, veterinary patient) or if adniinistered by feeding tube. °Intravenous tubing already attached and primed.



## 28

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