EXPOSURE TO ANTINEOPLASTIC AGENTS IN THE PHARMACY LABORATORY

EXPOSURE TO ANTINEOPLASTIC AGENTS IN THE PHARMACY LABORATORY SETTING AND ONGOING NIOSH STUDIES THOMAS H. CONNOR, Ph. D. Senior Service Fellow National Institute for Occupational Safety and Health Cincinnati, OH 513 -533 -8399 tmc 6@cdc. gov

EXAMPLES OF HAZARDOUS DRUGS l Antineoplastic l Antiviral agents l Hormonal agents l Immunosuppressant l Some antibiotics agents

DEFINITION OF HAZARDOUS DRUGS l Carcinogenicity l Teratogenicity/developmental l Reproductive toxicity l Organ toxicity at low doses l Genotoxicity l Structure/activity similar to known hazardous drug

ANTINEOPLASTIC AGENTS RECENT CONCERNS l More cancer patients l More combinations of drugs l Higher doses of drugs l More potent drugs l New procedures/settings

ANTINEOPLASTIC AGENTS l 80 -100 Agents Alkylating agents l Antibiotics l Antimetabolites l Biologicals l Hormonal agents l Monoclonal antibodies l Nitrogen mustard derivatives l Plant alkaloids l Others l

CARCINOGENICITY OF ANTINEOPLASTIC AGENTS IARC Classification Class 1 (human carcinogen) 9 plus 2 combinational therapies l Class 2 A (probable human carcinogen) 9 l Class 2 B (possible human carcinogen) 10 l Combinational therapies currently being evaluated by IARC l

POTENTIALLY EXPOSED GROUPS l l l l Workers in manufacturing Pharmacists and technicians Nursing personnel Physicians Operating room personnel Housekeeping and laundry personnel Veterinarians Retail pharmacists

NATURE OF THE PROBLEM l Primary concern is for the safety of the patient n Drugs must be prepared aseptically n Contamination can be fatal to the patient l Secondary concern is the safety of the healthcare worker n Exposure to hazardous drugs must be kept as low as possible n Many opportunities for exposure

WORKER PROTECTION Horizontal cabinets should not be used for hazardous drug preparation l Class II or Class III BSCs (+/-) must be used l Vented BSCs recommended l Leur-lock, needle-less and closed systems should be used for preparation and administration l

ROUTES OF EXPOSURE l INHALATION Droplets/particulates n Vapors n l DERMAL l ORAL

COMMON SOURCES OF EXPOSURE l l l DRUG PREPARATION n Drug dilution and transfer DRUG ADMINISTRATION n Priming tubing n Disconnecting lines n Instillation procedures DISPOSAL OF DRUGS AND WASTE n Emptying waste containers and cleaning contaminated areas

SURFACE CONTAMINATION STUDY l l l SIX CANCER CENTERS IN U. S. AND CANADA PHARMACIES AND TREATMENT AREAS THREE DRUGS-CP, FU, IF BSCs, COUNTERS, CARTS, FLOORS, CHAIRS, TABLES 75 % PHARMACY AND 65 % TREATMENT AREA SAMPLES POSITIVE FOR AT LEAST ONE DRUG ADJACENT AREAS CONTAMINATED Connor et al, AJHP (1999)

DRUG RECONSTITUTION WITH NEEDLE AND SYRINGE

DRUG TRANSFER WITH NEEDLE AND SYRINGE

OTHER SOURCES OF EXPOSURE l l l CONTACT WITH CONTAMINATED SURFACES n Drug vials, counter tops, keyboards, IV bags, tables, chairs, waste containers CONTAMINATION IN AREAS THOUGHT TO BE DRUG-FREE n Locations adjacent to work areas POSSIBLE PASSAGE THROUGH HEPA FILTERS n Vapors

FLOOR CONTAMINATION FROM CYCLOPHOSPHAMIDE SPILL NG/CM 2 DAYS

OCCUPATIONAL MONITORING l WIPE n Since l SAMPLES 1992, 13 studies reported in literature AIR SAMPLES n Since 1983, 12 studies reported in literature

OCCUPATIONAL MONITORING l WIPE n SAMPLES All studies that have used wipe samples to monitor environmental contamination have demonstrated measurable levels of the drugs. n 1 -5 Drugs sampled

OCCUPATIONAL MONITORING l WIPE SAMPLES n Drugs that are commonly used for wipe sample studies – Cyclophosphamide – Ifosfamide – Fluorouracil – Methotrexate

OCCUPATIONAL MONITORING l WIPE SAMPLES n Locations that have been sampled – Pharmacy and Preparation areas – Treatment Areas – Adjacent Areas

OCCUPATIONAL MONITORING l AIR SAMPLING n Drugs that are commonly used for air sampling – Cyclophosphamide – Ifosfamide – Fluorouracil

OCCUPATIONAL MONITORING l AIR n Air SAMPLING sampling often does not detect drugs or detects low levels of drugs n May be due to technical problems – Glass fiber or paper filter materials – Drugs in vapor phase

OCCUPATIONAL MONITORING l URINE ANALYSIS FOR SELECTED DRUGS n Most n In studies have been performed in Europe 18 studies, all but two studies detected drugs in the urine n In four studies, drugs were found in the urine of workers who were not handling them

OCCUPATIONAL MONITORING l URINE ANALYSIS FOR SELECTED DRUGS n Approximately n n 100 individuals/3 years 14 German hospitals Cyclophosphamide 40% Ifosfamide 14% Anthracyclines 4. 5% Pethran et al, Int Arch Occup Environ Health (2003)

DERMAL EXPOSURE PATHWAY l THREE WORKPLACE SURVEYS n Contamination from IV systems n Contamination from patient urine n Analysis of air particulates Kromhout et al, Ann Occup Health (2000)

SOURCES OF EXPOSURE l CONTAMINATION FROM PATIENT URINE n Added a fluorescent material to bedpans and urinals to track possible drug contamination n “Frequent and widespread contamination was seen…” n Soles of shoes n Skin of patients and nurses

CURRENT NIOSH ACTIVITIES l PERSONAL PROTECTIVE EQUIPMENT STUDY n ASTM n Four Standard for Chemotherapy Gloves drugs n Several types of glove/gown materials

CURRENT NIOSH ACTIVITIES l NIOSH ALERT ON HAZARDOUS DRUGS n All hazardous drugs n Focus on antineoplastic drugs n Release expected summer, 2003

CURRENT NIOSH ACTIVITIES l NIOSH WORKING GROUP ON HAZARDOUS DRUGS n NIOSH, OSHA, FDA, VA n ONS, ASHP, ASTM, ANA, JCAHO n PHARMACISTS, NURSES, HOME HEALTH CARE n DRUG, BSC MANUFACTURERS n RESEARCHERS

CURRENT NIOSH ACTIVITIES l OCCUPATIONAL EXPOSURE STUDY OF HEALTHCARE WORKERS n 3 -4 Institutions n Pharmacy n Minimum n Several and nursing personnel 50 exposed/50 non-exposed environmental and biological endpoints