Safe Handling of Hazardous Medications - CE

ALERT Don appropriate personal protective equipment (PPE) based on the patient’s signs and symptoms and indications for isolation precautions.

Refer to Oncology Nursing Society (ONS) interim guidelines for PPE recommendations during an emergent shortage of PPE (e.g., pandemic).3

Exposure to hazardous drugs (HDs) can create health risks, including genotoxicity, carcinogenicity, teratogenicity, fertility impairment, early pregnancy failure, and organ toxicity, in individuals who handle HDs during their procurement, transport, preparation, administration, or disposal.1 The potential for exposure during the handling of bodily fluids exists for at least 48 hours after medication administration and can last for up to 7 days after the administration of some HDs.1,4

Only health care team members who have shown competency in the preparation and handling of antineoplastic therapy should prepare or administer hazardous medications.

OVERVIEW A medication is considered hazardous if animal or human studies indicate that exposure creates a health risk.1 HDs may include antineoplastic, biotherapeutic, immunosuppressive, and antiviral agents; targeted therapies; certain hormones and antibiotics; and drugs in other classes. A safe level of exposure to these medications has not been determined.1 HDs may be administered across a variety of patient care areas in today’s health care settings and all individuals should be aware of their risks.

HDs can adversely affect the health of those exposed through direct or indirect contact. HD exposure can result in genetic damage, which may lead to long-term health effects, including cancer and reproductive abnormalities. Other effects of HD exposure include skin, eye, mucous membrane, and lung irritation; nausea; vomiting; blood disorders; malignancies; fetal abnormalities; low birth weight; and spontaneous abortions. HD awareness and mitigation are commonly associated with chemotherapy, or antineoplastic, drugs. However, many other drugs also pose risks to health care team members (Box 1).

Box 1 Hazardous Nonantineoplastic Medications • abacavir • estradiol • medroxyprogesterone • progestins • alefacept • estrogen–progestin acetate • propylthiouracil • apomorphine combinations • methimazole • raloxifene • azathioprine • estrogens, conjugated • mipomersen • rasagiline • carbamazepine estrogens, esterified • mycophenolate mofetil • sirolimus • chloramphenicol • estropipate • mycophenolic acid • spironolactone • cidofovir • fingolimod • nevirapine • tacrolimus • cyclosporine • fluoxymesterone • ospemifene • teriflunomide • deferiprone • fosphenytoin • oxcarbazepine • thalidomide • dexrazoxane • ganciclovir palifermin • tofacitinib • diethylstilbestrol • leflunomide • phenoxybenzamine • uracil mustard • divalproex • lenalidomide • phenytoin • valganciclovir • entecavir • liraglutide recombinant • progesterone • zidovudine (Adapted from National Institute for Occupational Safety and Health [NIOSH]. [2016]. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, 2016. Retrieved April 3, 2020, from https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf?id=10.26616/NIOSHPUB2016161)

Safe Handling of Hazardous Medications - CE

Medications that are primarily hazardous to reproductive processes are categorized separately (Box 2). The risks associated with these medications apply to both males and females.

Box 2 Nonantineoplastic Medications That Can Cause Adverse Reproductive Effects • acitretin • fluconazole • plerixafor • alitretinoin • ganirelix • ribavirin • ambrisentan • gonadotropin, chorionic • riociguat • bosentan • icatibant • temazepam • cabergoline • lomitapide • testosterone • cetrorelix • macitentan • topiramate • choriogonadotropin • menotropins • tretinoin • clomiphene • methyltestosterone • ulipristal • clonazepam mifepristone • valproate, valproic acid • colchicine • misoprostol • vigabatrin • dinoprostone • nafarelin • voriconazole • dronedarone • oxytocin • warfarin • dutasteride • pamidronate • ziprasidone • ergonovine– • paroxetine • zoledronic acid methylergonovine • pasireotide • zonisamide • eslicarbazepine • peginesatide • finasteride • pentetate calcium trisodium (Adapted from National Institute for Occupational Safety and Health [NIOSH]. [2016]. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, 2016. Retrieved April 3, 2020, from https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf?id=10.26616/NIOSHPUB2016161)

The United States Pharmacopeial Convention (USP), an organization that sets standards for medication quality, has issued new standards on all types of medications and exposures to them. These new standards describe safe handling of HDs. The expectation is that the new USP recommendations will be enforced beginning in December 2019.5 Other organizations that develop guidelines aimed at promoting safe handling of HDs include the Occupational Safety and Health Administration, the National Institute for Occupational Safety and Health (NIOSH), the American Society of Health-System Pharmacists, and the Oncology Nursing Society.

Exposure can occur during routine medication and patient care activities (Table 1). Pathways include inhalation, ingestion, injection, and touch.1 Inhalation can occur when powder creates dust and when air expelled from tubing and syringes generates aerosols. Exposure can occur via ingestion with eating, drinking, smoking, and applying cosmetics. The use of personal protective equipment (PPE), including a chemotherapy-resistant gown, chemotherapy-tested gloves, and a face shield or eye protection when there is risk of splashing, is recommended during the preparation and administration of HDs to significantly reduce the incidence of adverse health effects.6 Respiratory protection may also be worn per the organization’s practice when there is a risk of aerosolization. An appropriate full- facepiece, chemical cartridge-type respirator or a powered air-purifying respirator (PAPR) should be donned when a risk of respiratory exposure to HDs exists.6 Standard N95 respirator masks used in airborne precautions do not protect against gases and vapors.6

Table 1 Activities Resulting in Exposure to Hazardous Drugs Type of activity Examples Compounding and • Crushing or splitting tablets or opening capsules other manipulations • Pouring oral or topical liquids from one container to another

Safe Handling of Hazardous Medications - CE

• Weighing or mixing components • Constituting or reconstituting powdered or lyophilized HDs • Withdrawing or diluting injectable HDs from parenteral containers • Expelling air or HDs from syringes • Contacting HD residue on PPE or other garments • Deactivating, decontaminating, cleaning, and disinfecting areas contaminated with or suspected to be contaminated by HDs • Performing maintenance activities for potentially contaminated equipment and devices Administration • Generating aerosols during administration of HDs by various routes (e.g., injection, irrigation, oral, inhalation, or topical application) • Performing certain specialized procedures (e.g., intraoperative intraperitoneal injection or bladder instillation) • Priming an IV administration set Patient-care • Handling bodily fluids (e.g., urine, feces, sweat, or vomit) or activities bodily fluid–contaminated clothing, dressings, linens, and other materials Spills • Being involved with spill generation, management, and disposal Transport • Moving HDs within a health care setting Waste • Collecting and disposing of hazardous waste and trace contaminated waste HD, hazardous drug; PPE, personal protective equipment (Adapted from United States Pharmacopeial Convention [USP]. [2019]. USP general chapter <800>: Hazardous drugs—Handling in healthcare settings. Retrieved April 3, 2020, from http://www.usp.org)

Hazardous medications or metabolites are excreted in patients’ urine or feces but may also be present in other body fluids, including blood, emesis, vaginal fluids, semen, and tears. Although the risk of exposure is low when handling bodily fluids of patients who have received HDs, exposure is still possible. Health care team members who handle bodily secretions or linens soiled with them should demonstrate competence in safe handling of the linens. Those who may be exposed include dietary, housekeeping, and laundry personnel, in addition to direct health care providers. Such personnel must wear PPE when handling bodily fluids and linens for at least the first 48 hours after the completion of drug administration.4 Some drug metabolites have been detected in urine and feces up to 7 days after drug administration.2

Nurses should understand the definition of HDs, routes of exposure, toxicities associated with exposure, and interventions to minimize exposure for themselves and other health care team members. Nurses should also be able to educate patients and caregivers regarding safe practices at home. Organizations should have evidence-based standards of practice, policies, and training that comply with regulatory requirements to manage HDs.4

EDUCATION • Tell the patient and family which medications to be administered are considered hazardous. • Explain that exposure may occur through several routes, including direct contact with the skin, inhalation, ingestion, and injection. • Teach the patient and family about the hazards and the ways to manage them for all medications that will be prescribed upon discharge. • Explain the need for PPE during the administration and handling of HDs.

Safe Handling of Hazardous Medications - CE

• Explain why HD precautions must be observed for at least 48 hours after administration; explain that precautions are ongoing if oral agents are taken at home for a lengthy period.4 • Instruct the patient regarding the potential side effects and adverse reactions of the medication. • Instruct the patient to discuss with the practitioner whether sexual contact with a partner is safe. The patient should use a condom during sexual contact because hazardous drug metabolites are found in saliva, semen, and vaginal secretions.4 • Encourage questions and answer them as they arise.

ASSESSMENT AND PREPARATION Assessment 1. Perform hand hygiene and don PPE as indicated for needed isolation precautions. 2. Introduce yourself to the patient. 3. Verify the correct patient using two identifiers. 4. Assess the patient for specific contraindications to receiving the HD and advise the practitioner accordingly. 5. Determine whether the patient and family understand the purpose and rationale for administering HD therapy. 6. Determine whether the patient and family have specific questions or concerns about HD therapy. 7. Complete a health history and physical examination that includes, at a minimum, height, weight in kilograms, and an assessment of organ-specific functions as appropriate for the planned regimen.2

Preparation 1. Before collecting the ordered medications, review the medication administration record to determine if any are HDs. 2. Initiate precautions for patients receiving HDs.

Rationale: Precautions are designed to minimize indirect exposure with bodily fluids (e.g., blood, urine, feces, emesis).

The preparation of the HD has no bearing on its hazardous status; oral preparations of hazardous agents are as hazardous as IV preparations. a. Comply with the organization’s practice regarding PPE for handling and administering HDs. Use the ONS interim guidelines for PPE recommendations during an emergent shortage of PPE (e.g., pandemic) (Table 2).3

Table 2 Oncology Nursing Society (ONS) Recommendations and Interim Guidelines for Personal Protective Equipment (PPE) Use During Pandemic PPE ONS recommendations* Pandemic interim guidelines (in descending order) Gown Disposable poly-coated gown • Regular disposable gown (water resistant) • Cloth gown (facility laundered) for infection control and nonhazardous drugs

Safe Handling of Hazardous Medications - CE

Mask Mask with face and eye • N95 mask for symptomatic or patients protection required only if with COVID-19 and hazardous drug splashing likely and for spill spills and cleanup cleanup • PAPR Eye protection Mask with eye protection or • Full facepiece air-purifying respirator googles if splashing likely or or PAPR spill cleanup Gloves Double chemotherapy-tested • Single chemotherapy-tested gloves gloves • Double standard examination gloves • Single standard examination gloves Shoe covers Only in area for compounding • Work-only, washable shoes hazardous drugs COVID, coronavirus; PAPR, powered air purifying respirator; PPE, personal protective equipment *Highest-level recommended practice based on supplies of available PPE (Data from Oncology Nursing Society. [ONS]. [2020]. ONS interim guidelines during the COVID-19 pandemic. Retrieved on April 3, 2020, from https://www.ons.org/covid-19-interim-guidelines) i. PPE consists of a chemotherapy-resistant gown, two pairs of chemotherapy-tested gloves, and a mask or face shield. PPE may also include a respirator.4,6 ii. Other equipment may include a closed-system transfer device (CSTD), a device that allows medication administration with a reduced risk of leaking or spilling. iii. One pair of chemotherapy-tested gloves may be used with no other PPE when administering intact oral capsules or tablets.4 b. Wear PPE when handling the bodily fluids and linens of patients. c. Avoid splashing bodily fluids and wear a face shield if splashing is possible. d. Place linens contaminated with bodily fluids in a specially marked, impervious laundry bag. e. If the patient is incontinent, use absorbent materials, such as incontinence pads, to contain his or her bodily fluids. Cleanse the skin and apply a barrier cream after each incontinence pad change. f. Cover the toilet seat with an absorbent, plastic-backed pad when flushing the toilet after use by a patient who is within the precautionary period; dispose of the pad in a hazardous waste container.

PROCEDURE 1. Perform hand hygiene and don gloves and appropriate PPE based on the patient’s signs and symptoms and indications for isolation precautions. Use the ONS interim guidelines for PPE recommendations during an emergent shortage of PPE (e.g., pandemic) (Table 2).3 2. When no PPE shortage exists, don two pairs of chemotherapy-tested gloves. Don a chemotherapy-resistant gown and face shield or eye protection per the organization’s practice or if a risk of spilling or splashing of HDs or their waste materials exists.6

Rationale: Two pairs of chemotherapy-tested gloves should be worn when handling HDs, including nonantineoplastics and reproductive–risk-only HDs. One pair of chemotherapy-tested gloves may be used with no other PPE when administering intact oral capsules or tablets.4 Many HDs are irritating to the eyes and mucous membranes.6

3. Verify the correct patient using two identifiers. 4. Explain the procedure to the patient and ensure that he or she agrees to treatment.

Safe Handling of Hazardous Medications - CE

5. Don respiratory protection per the organization’s practice. Wear an appropriate full- facepiece, chemical cartridge-type respirator or a powered air-purifying respirator (PAPR) when a risk of respiratory exposure to HDs exists.6

Standard N95 respirator masks used in airborne precautions do not protect against gases and vapors.6

6. Inspect the packaging of the HDs for leakage. Ensure that the packaging is sealed and that roller clamps (if any) are secured. 7. Avoid crushing a tablet, opening a capsule, or manipulating the medication in any way, if possible. If manipulation cannot be avoided, don appropriate PPE before manipulation.6 8. If the HD will be administered as an IV infusion, place a plastic-backed absorbent pad under the tubing. If the HD will be administered by IV push, place sterile gauze around the push sites. 9. Use a CSTD, if available, for administration. If a CSTD is unavailable, use Luer lock fittings.

Rationale: A CSTD attached to the tubing prevents leakage during disconnection.

10. Flush the IV tubing completely with a nonhazardous, compatible fluid before disconnecting it.

Consult a drug guide or follow the organization’s practice to ensure that compatible fluid is used to flush the tubing.

11. Disconnect the IV tubing from the patient. Use the CSTD attached to the tubing during disconnection. If a CSTD is not available, use an absorbent pad beneath the connection or wrap the connection with sterile gauze.

Rationale: An absorbent pad or sterile gauze absorbs an HD if leakage occurs.

12. Place the tubing, bags, absorbent pads, gauze, and any other supplies used during HD administration in a sealable plastic bag.

Do not disconnect the tubing from the IV bag; dispose of the tubing and the bag as one unit.

13. Ensure that HDs are disposed of according to the organization’s practice. a. Disposal containers should be labeled “hazardous waste,” be single-use only, and have a tight-fitting lid.

Keep the hazardous waste container’s lid closed at all times. Do not overfill the container. b. Disposal will vary based on the medication’s properties. Liquids may be placed in a separate container from solid waste. c. Notify the appropriate personnel when the hazardous waste container is full.

14. Place syringes and needles directly into a puncture-proof hazardous waste container.

Safe Handling of Hazardous Medications - CE

Do not break or recap the needles.

15. Remove PPE. Remove the outer set of gloves first, then the face shield, then the gown, followed by the inner set of gloves. 16. Dispose of the PPE in the appropriate hazardous waste container. 17. Perform hand hygiene. 18. Remove the respirator, if worn, without touching the facepiece and dispose of it. Perform hand hygiene if contaminated during removal. 19. Document the procedure in the patient’s record.

MONITORING AND CARE 1. Initiate exposure interventions after direct contact with an HD, per the organization’s practice. 2. Evacuate those not involved in the exposure area. Use a NIOSH-approved respirator (N95 or above) for protection during the cleanup. Determine the size of the spill and follow the organization’s practice for cleanup.

Specialty teams often handle spills of substantial size.

3. Have those who were exposed take these steps. a. Remove contaminated clothing immediately. b. If the skin is exposed, wash the area with nongermicidal soap and water. c. If the eye is exposed, flush with water or isotonic eyewash thoroughly with the affected eyelid open. d. Seek immediate medical attention.

4. File an incident or event report per the organization’s practice. 5. Assess, treat, and reassess pain.

EXPECTED OUTCOMES • HDs are administered correctly. • Proper PPE is used. • No direct exposure to HDs occurs. • No indirect exposure to HDs occurs. • HD spills are contained appropriately. • HDs are discarded appropriately.

UNEXPECTED OUTCOMES • HD is administered incorrectly. • Proper PPE is not worn. • Exposure to an HD occurs. • HD spills are not contained appropriately. • HDs are not discarded appropriately.

DOCUMENTATION • Incident or event report for direct or indirect exposure or spill • Date and time of administration of HDs, including time initiated and time discontinued • Education and response to education

Safe Handling of Hazardous Medications - CE

• Patient’s response to medication, including adverse effects • Patient and family adherence to safe handling requirements • Psychosocial support provided • Unexpected outcomes and related interventions

SPECIAL CONSIDERATIONS • Health care team members who are pregnant, actively trying to conceive (whether male or female), or breastfeeding should be allowed to refrain from preparing or administering HDs and from caring for patients receiving HDs per the organization’s practice.4 • Patients who have fecal or urinary incontinence have an increased risk of exposure to HDs. Make efforts to contain their bodily fluids. • All health care team members who may come into contact with HDs should be trained in safe handling techniques. Health care team members include registered nurses, licensed practical nurses, nursing assistants, other ancillary practitioners, and housekeeping, laundry, and dietary personnel.

REFERENCES 1. National Institute for Occupational Safety and Health (NIOSH). (2016). NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, 2016. Retrieved April 3, 2020, from https:/www.cdc.gov/niosh/docs/2016-161/ (Level VII) 2. Neuss, M.N. and others. (2017). 2016 updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards, including standards for pediatric oncology. Oncology Nursing Forum, 44(1), 31-43. doi:10.1188/17.ONF.31-43 (Level VII) 3. Oncology Nursing Society (ONS). (2020). ONS interim guidelines during the COVID-19 pandemic. Retrieved April 3, 2020, from https://www.ons.org/covid-19-interim-guidelines (Level VII) 4. Polovich, M. (2019). Chapter 12: Safe handling of hazardous drugs. In M.M. Olsen, K.B. LeFebvre, K.J. Brassil (Eds.), Chemotherapy and immunotherapy guidelines and recommendations for practice (pp. 235-250). Pittsburgh: Oncology Nursing Society. (Level VII) 5. United States Pharmacopeial Convention (USP). (2019). USP <800> FAQs. Retrieved April 3, 2020, from https://www.usp.org/sites/default/files/usp/document/our- work/compounding/faqs-usp-800.pdf (Level VII) 6. United States Pharmacopeial Convention (USP). (2019). USP general chapter <800>: Hazardous drugs – Handling in healthcare settings. Retrieved April 3, 2020, from http://www.usp.org (Level VII)

ADDITIONAL READINGS Oncology Nursing Society. (2018). Toolkit for safe handling of hazardous drugs for nurses in oncology. Retrieved April 3, 2020, from https://www.ons.org/sites/default/files/2018- 06/ONS_Safe_Handling_Toolkit_0.pdf Power, L.A., Coyne, J.W. (2018). ASHP guidelines on handling hazardous drugs. AJHP: American Journal of Health-System Pharmacy™, 75(24), 1996-2031. doi:10.2146/ajhp180564

Safe Handling of Hazardous Medications - CE

Elsevier Skills Levels of Evidence • Level I - Systematic review of all relevant randomized controlled trials • Level II - At least one well-designed randomized controlled trial • Level III - Well-designed controlled trials without randomization • Level IV - Well-designed case-controlled or cohort studies • Level V - Descriptive or qualitative studies • Level VI - Single descriptive or qualitative study • Level VII - Authority opinion or expert committee reports

SUPPLIES • HD waste container • PPE o For isolation precautions: gloves and PPE, as indicated o For antineoplastic administration: double chemotherapy-tested gloves, eye protection, face shield, impervious chemotherapy-resistant gown with long sleeves that closes in the back, and respirator • Impervious laundry bag • Plastic absorbent pads • Puncture-proof, leakproof container labeled “Hazardous Waste” • Sealable plastic bags • Spill kit that includes shoe covers, chemical splash eye protection or face shield, NIOSH- approved respirator masks, plastic scraper and dustpan, puncture-proof container for glass, chemotherapy-resistant gowns with back closure, chemotherapy gloves, heavy- duty waste sealable disposal bags, hazardous waste label • Sterile gauze • CSTD

Author: Nancy Ehmke, RN, MN, AOCN® Clinical Review: Heather T. Mackey, MSN, RN, ANP-BC, AOCN® Revised: Heather T. Mackey, MSN, RN, ANP-BC, AOCN®

Published: March 2020 Revised: April 2020