48 th Annual Meeting. Safe Handling of Hazardous Medications. Background. Background. Disclosure. Hazardous Agents. Objectives 7/20/2014

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1 48 th Annual Meeting Safe Handling of Hazardous Medications Melissa Butler, PharmD, BCOP Clinical Pharmacist, Oncology UF Health Cancer Center Orlando Health Navigating the Oceans of Opportunity Background 1940s first case reports of use of nitrogen mustard and methotrexate for treatment of cancer 1960s combination chemotherapy produces cures Childhood acute lymphocytic leukemia Adult advanced Hodgkin s lymphoma 1970s concerns for occupational exposure arose Carcinogen in animal models Reports of new cancers/precancerous lesions arising in patients previously treated with chemotherapy Immunosuppressive agents linked to increased risk of cancer Genetic mutations in bacteria in urine of nurses administering chemotherapy Cancer Res 2008;68(21): Cancer 1976;37: Lancet 1979;1(12): Am J Health Syst Pharm 1978; 35:900 Disclosure Background I do not have a vested interest in or affiliation with any corporate organization offering financial support or grant monies for this continuing education activity, or any affiliation with an organization whose philosophy could potentially bias my presentation 1980s first recommendations for safe handling issued Risk for exposure is increasing with use of hazardous for non-malignant diseases National Institute for Occupational Safety and Health (NIOSH) generated list Antineoplastic agents Antiviral agents Biological modifiers Hormonal agents Accessed April 30, 2014 Objectives Hazardous Agents Recognize agents classified as hazardous Discuss the risks associated with accidental exposure to hazardous List the various stages during handling of hazardous when accidental exposure can occur Describe methods utilized to decrease accidental exposure of hazardous Hazardous exhibit one or more of the following characteristics in humans/animals: Carcinogenicity Teratogenicity or other developmental toxicity Reproductive toxicity Organ toxicity at low doses Genotoxicity Structure and toxicity profiles of new drugs that mimic existing drugs determined hazardous by the above criteria Occupational Safety and Health Administration (OSHA) requires employers to evaluate practice-specific and post list for employee review 1

2 Resources for Determination of Hazardous Status Package inserts for pharmaceutical agents Material safety data sheets (MSDS) American Hospital Formulary Service (AHFS) Pharmacologic- Therapeutic Classification System PharmEcology National Toxicology Program s Report on Carcinogens (NTRPC) International Agency for Research on Cancer (IARC) Published literature NIOSH Data Supporting Cyclophosphamide Malignancies associated with treatment Genetic mutations associated with treatment Fetal abnormalities reported with use during pregnancy Reported side effects Myelosuppression Amenorrhea Sterility/infertility Cytoxan [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; Accessed May 20, Examples of NIOSH-listed Hazardous Medications Generic Name Brand Name Drug Class Capecitabine Xeloda Antineoplastic Cisplatin Platinol Antineoplastic Cyclophosphamide Cytoxan Antineoplastic Doxorubicin Adriamycin Antineoplastic Fluorouracil Adrucil Antineoplastic Methotrexate Trexall Antineoplastic Paclitaxel Taxol Antineoplastic Thalidomide Thalomid Antineoplastic Vincristine Oncovin Antineoplastic Data Supporting Anastrozole Decreased number of implantations and increased postimplantation fetal loss in rat models at doses x maximum recommended clinical doses Associated with spontaneous abortions in rabbit models Increased risk of cancer in rat models at doses x higher than dose used clinically Arimidex [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; Accessed May 19, Examples of NIOSH-listed Hazardous Medications Generic Name Brand Name Drug Class Anastrozole Arimidex Aromatase inhibitor Azathioprine Imuran, Azasan Immunosuppressant Carbamazepine Carbatrol, Tegretol(XR), Epitol, Anticonvulsant Equetro Colchicine Colcrys Antigout agent Dasatinib Sprycel Tyrosine kinase inhibitor Dronedarone Multaq Antiarrhythmic Estrogen/progestins Hormonal agents Finasteride Proscar, Propecia 5-alpha reductase inhibitor Ganciclovir Cytovene, Vitrasert, Zirgan Antiviral Raloxifene Evista Selective estrogen receptor modulator Risperidone Risperdal Antipsychotic Warfarin Coumadin, Jantoven Anticoagulant Zidovudine Retrovir Antiretroviral Zoledronic acid Zometa, Reclast Bisphosphonate Data Supporting Colchicine Observed side effects: Myelosuppression Aplastic anemia Oligospermia/azospermia Theoretical concern for carcinogenicity Embryofetal toxicity, teratogenicity, and altered postnatal development at exposures within or above the clinical therapeutic range in animal models No adverse effects observed with use during pregnancy No published adverse effects with breastfeeding Colcrys [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc; Accessed May 19,

3 Hazardous Classification Routes of Exposure Cyclophosphamide Anastrozole Colchicine NIOSH X X X AHFS X X PharmEcology X X Package insert X X X IARC X MSDS X X X NTRPC X Inhalation Accidental injection Ingestion Dermal and mucosal absorption Key Points to Remember Different levels of protection required based on individual factors Factors contributing to risk of exposure Dosage formulation Alteration of dosage formulation Packaging Environment Personal protective equipment (PPE) Activities Associated with Potential for Exposure Receiving and unpacking Counting/repackaging individual oral doses and tablets from bulk containers Crushing tablets/opening capsules to make liquid formulations Pouring oral or topical liquids Mixing topical dosage forms Weighing or mixing components Withdrawing or diluting injectable Possible Sources of Exposure Lack of vigilance in work practices Poor adherence to PPE Contaminated vials and/or packaging Spills Lack of awareness of the issue Sources yet to be identified Activities Associated with Potential for Exposure Constituting/reconstituting powdered or lyophilized Expelling air from syringes Expelling hazardous from a syringe Contacting residues on drug containers, work surfaces, floors, and final drug preparations Contacting or inhaling residues or aerosolization from another patient s Administration of hazardous 3

4 Activities Associated with Potential for Exposure Priming IV tubing with a solution containing hazardous Handling contaminated waste Deactivating, decontaminating, cleaning and disinfecting areas contaminated with hazardous Maintenance of potentially contaminated equipment Spill generation, management, and subsequent disposal of clean-up materials Studies Examining Effects on Fertility/Birth Weight, correlational Questionnaire 2427 nurses 3399 offspring Survey 4393 nurses Determine the effects of chemotherapy handling among nurses and their offspring Determine reproductive effects of exposure Handling age <25 increased risk of infertility More years of handling associated with higher rates of miscarriage Handling 9+ doses/day increased risk of preterm labor and early birth Learning disabilities increased in offspring of nurses who rarely wore PPE Increased risk of cancer among exposed nurses Nurses highly exposed took longer to conceive Exposure associated with premature delivery and low birth weight Oncol Nurs Forum. 2005;32:425. Epidemiology. 2007;18: Potential Acute Effects from Exposure Contact dermatitis/skin irritation Ocular irritation Headaches/dizziness Abdominal pain Cough Hair thinning Menstrual cycle disruption Fetal loss Low birth weight infants Potential Long-term Effects from Exposure Possible increased risk Infertility Cancer Inconsistent findings across studies Assessed via surrogate markers Urine samples for mutagenicity and detection of hazardous Peripheral blood for micronuclei and chromosomal abnormalities Drugs-in-Healthcare.pdf. Accessed May 29, Studies Examining Effects on Fertility/Birth Weight Matched case-controlled Questionnaire 466 nurses 420 live births Determine relationship between birth weight and exposure during and before pregnancy No difference in birth weigh Questionnaire 2976 pharmacists/nurses 7094 pregnancies Determine effect of exposure on pregnancy loss Exposure directly before or during pregnancy associated with an increased risk of spontaneous abortion/stillbirth Studies Examining Risk of Cancer Retrospective review 1282 exposed nurses 2572 unexposed nurses Archived analysis Female pharmacy technicians in Danish cancer registry Describe risk for cancer Determine cancer incidence among hazardous drug handlers Significantly increased relative risk for leukemia 1.5 fold elevated risk of nonmelanoma skin cancer 3.7 fold elevated risk for non- Hodgkin s lymphoma Retrospective review 1282 exposed nurses 2572 unexposed nurses Describe reproductive outcomes No increased risk for adverse reproductive outcomes Blood samples and questionnaires 91 exposed nurses 54 unexposed controls Determine the occurrence of DNA damage in nurses handling hazardous 50% higher level of DNA damage detected in nurses not using PPE No difference between controls and nurses using PPE Scand J Work Environ Health. 1993;19: J Occup Environ Med. 1999;41: Br J Ind Med. 1992;49: Br J Ind Med. 1992;49: Scand J Work Environ Health. 1994;20:22-6. Mutat Res. 1995;342:

5 Studies Examining Risk of Cancer Air Flow in a Class II BSC Drug handling log Urine samples Scans for doxorubicin contamination 23 exposed pharmacists 60 exposed nurses 35 controls Analyze internal and external exposure 15% urine samples positive for mutagenicity (related to reported skin exposure) 13% scans positive for exposure more contamination reported with administration than preparation (reported PPE 27% among nurses) Laboratory analysis Blood and mucosal samples evaluated from 25 exposed nurses, 5 pharmacy technicians, 30 controls Evaluate genotoxic effects of antineoplastic exposure No difference between exposed and control blood samples Higher values of micronuclei in mucosal samples of exposed workers Chromosomal abnormalities were 2.5-5x higher in exposed groups Cancer Nurs. 1998;21: Scand J Work Environ Health. 1994;20:22-6. Mutat Res. 1995;342: Key Points to Remember Air Flow in a CACI Small sample sizes Majority of studies are retrospective Inconsistent findings PPE not routinely utilized in early studies Personal history may not have been accounted for Surrogate markers utilized Methods to Decrease Exposure Administrative controls Policies and procedures Training and validation of competency Quality improvement programs Environmental and engineering controls High-efficiency particulate air (HEPA) filters Biologic safety cabinets (BSC) Compounding aseptic containment isolators (CACI) Buffer and ante areas Closed-system drug transfer devices Methods to Decrease Exposure Administrative controls Policies and procedures Training and validation of competency Quality improvement programs Environmental and engineering controls High-efficiency particulate air (HEPA) filters Biologic safety cabinets (BSC) Compounding aseptic containment isolators (CACI) Buffer area Ante area Closed-system drug transfer devices (CSDTD) 5

6 CSDTD Disposal of Waste Materials Device that mechanically prevents transfer of environmental contaminants into system and escape of drug/vapor from system Significantly reduce surface contamination with hazardous Reduce exposure to hazardous when used in combination with PPE and BSC Hosp Pharm. 1999;34: Am J Health-Syst Pharm. 2002;59(1): Am J Health-Syst Pharm. 2003;60(22): Methods to Decrease Exposure Work practice controls Gather all needed supplies before admixture Proper compounding technique Change gloves every 30 minutes or if contaminated Proper removal of PPE Proper disposal of waste Proper cleansing of work area PPE Gowns Double gloving Head/hair and shoe covers Face masks/goggles (respirators for spills) Decontaminating/Cleaning of Equipment No single product deactivates all currently available hazardous drugs SurfaceSafe contains a system for deactivation and decontamination Clean BSC at the beginning of the day and at regular intervals or at end of day Consider wiping down all materials before placing in BSC and final product Methods to Decrease Exposure Utilize PPE when handling vials Label storage areas as hazardous Separate hazardous from other drug inventory Store hazardous in areas with adequate ventilation Have spill kits readily available Properly clean equipment Properly dispose of waste materials Medical Surveillance NIOSH recommendation for primary and secondary prevention of adverse health events Augments and evaluates current protection processes Recommended process Medical and reproductive health questionnaires History of drug handling Medical history, physical exam, laboratory testing Follow-up plan as needed 6

7 Employer Actions if Trend Occurs Evaluate current protective measures Verify proper operating conditions Verify worker compliance with existing policies Develop plan to prevent further work exposure Offer alternative duty/temporary reassignment Provide ongoing medical surveillance Thank you for your time and attention! Summary Medications are classified as hazardous for various reasons Adequate knowledge of associated risks is essential for personal safety Various unexpected surfaces have been shown to be contaminated with hazardous Proper deactivation, decontamination, and cleaning processes decrease risk of exposure Summary Proper disposal of potentially contaminated materials is important to minimize exposure Proper use of PPE, BSC, CSDTD have shown to significantly decrease exposure to hazardous Knowledge = safety 7