Transcript MONITORING OCCUPATIONAL EXPOSURE TO …

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 [email protected]
EXAMPLES OF HAZARDOUS
DRUGS
 Antineoplastic
 Antiviral
agents
agents
 Hormonal
agents
 Immunosuppressant
 Some
antibiotics
agents
DEFINITION OF HAZARDOUS
DRUGS
 Carcinogenicity
 Teratogenicity/developmental
 Reproductive
toxicity
toxicity
 Organ toxicity at low doses
 Genotoxicity
 Structure/activity similar to known
hazardous drug
ANTINEOPLASTIC AGENTS
RECENT CONCERNS

More cancer patients

More combinations of drugs

Higher doses of drugs

More potent drugs

New procedures/settings
ANTINEOPLASTIC AGENTS

80-100 Agents
Alkylating agents
 Antibiotics
 Antimetabolites
 Biologicals

Hormonal agents
 Monoclonal
antibodies
 Nitrogen mustard
derivatives
 Plant alkaloids
 Others
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CARCINOGENICITY OF
ANTINEOPLASTIC AGENTS
IARC Classification
Class 1 (human carcinogen) 9 plus 2
combinational therapies
 Class 2A (probable human carcinogen) 9
 Class 2B (possible human carcinogen) 10
 Combinational therapies currently being
evaluated by IARC
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POTENTIALLY EXPOSED
GROUPS
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Workers in manufacturing
Pharmacists and technicians
Nursing personnel
Physicians
Operating room personnel
Housekeeping and laundry personnel
Veterinarians
Retail pharmacists
NATURE OF THE PROBLEM

Primary concern is for the safety of the patient
 Drugs
must be prepared aseptically
 Contamination can be fatal to the patient

Secondary concern is the safety of the
healthcare worker
 Exposure
to hazardous drugs must be kept as low
as possible
 Many opportunities for exposure
WORKER PROTECTION
Horizontal cabinets should not be used for
hazardous drug preparation
 Class II or Class III BSCs (+/-) must be used
 Vented BSCs recommended
 Leur-lock, needle-less and closed systems
should be used for preparation and
administration
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ROUTES OF EXPOSURE

INHALATION


Droplets/particulates
Vapors

DERMAL

ORAL
COMMON SOURCES OF
EXPOSURE

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
DRUG PREPARATION
 Drug dilution and transfer
DRUG ADMINISTRATION
 Priming tubing
 Disconnecting lines
 Instillation procedures
DISPOSAL OF DRUGS AND WASTE
 Emptying waste containers and cleaning
contaminated areas
SURFACE CONTAMINATION
STUDY
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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
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CONTACT WITH CONTAMINATED SURFACES
 Drug vials, counter tops, keyboards, IV bags,
tables, chairs, waste containers
CONTAMINATION IN AREAS THOUGHT TO BE
DRUG-FREE
 Locations adjacent to work areas
POSSIBLE PASSAGE THROUGH HEPA FILTERS
 Vapors
FLOOR CONTAMINATION FROM
CYCLOPHOSPHAMIDE SPILL
80
70
60
50
NG/CM2 40
30
20
10
0
0
28
56
84
DAYS
112
140
168
OCCUPATIONAL MONITORING
 WIPE
 Since

SAMPLES
1992, 13 studies reported in literature
AIR SAMPLES
 Since
1983, 12 studies reported in literature
OCCUPATIONAL MONITORING
 WIPE

SAMPLES
All studies that have used wipe samples to
monitor environmental contamination have
demonstrated measurable levels of the drugs.
 1-5
Drugs sampled
OCCUPATIONAL MONITORING
 WIPE
SAMPLES
 Drugs
that are commonly used for wipe sample
studies
– Cyclophosphamide
– Ifosfamide
– Fluorouracil
– Methotrexate
OCCUPATIONAL MONITORING
 WIPE
SAMPLES
 Locations
that have been sampled
– Pharmacy and Preparation areas
– Treatment Areas
– Adjacent Areas
OCCUPATIONAL MONITORING
 AIR
SAMPLING
 Drugs
that are commonly used for air sampling
– Cyclophosphamide
– Ifosfamide
– Fluorouracil
OCCUPATIONAL MONITORING
 AIR
 Air
SAMPLING
sampling often does not detect drugs or
detects low levels of drugs
 May
be due to technical problems
– Glass fiber or paper filter materials
– Drugs in vapor phase
OCCUPATIONAL MONITORING
 URINE ANALYSIS
FOR SELECTED
DRUGS
 Most
 In
studies have been performed in Europe
18 studies, all but two studies detected drugs in
the urine
 In
four studies, drugs were found in the urine of
workers who were not handling them
OCCUPATIONAL MONITORING

URINE ANALYSIS FOR SELECTED DRUGS
 Approximately
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100 individuals/3years
14 German hospitals
Cyclophosphamide 40%
Ifosfamide 14%
Anthracyclines 4.5%
Pethran et al, Int Arch Occup Environ Health
(2003)
DERMAL EXPOSURE PATHWAY
 THREE WORKPLACE SURVEYS
 Contamination from IV systems
 Contamination from patient urine
 Analysis of air particulates
Kromhout et al, Ann Occup Health (2000)
SOURCES OF EXPOSURE
 CONTAMINATION
FROM PATIENT
URINE
 Added
a fluorescent material to bedpans and
urinals to track possible drug contamination
 “Frequent and widespread contamination was
seen…”
 Soles of shoes
 Skin of patients and nurses
CURRENT NIOSH ACTIVITIES
 PERSONAL
PROTECTIVE
EQUIPMENT STUDY
 ASTM
 Four
Standard for Chemotherapy Gloves
drugs
 Several
types of glove/gown materials
CURRENT NIOSH ACTIVITIES
 NIOSH ALERT
ON HAZARDOUS
DRUGS
 All
hazardous drugs
 Focus
on antineoplastic drugs
 Release
expected summer, 2003
CURRENT NIOSH ACTIVITIES
 NIOSH
WORKING GROUP ON
HAZARDOUS DRUGS
 NIOSH,
OSHA, FDA, VA
 ONS, ASHP, ASTM, ANA, JCAHO
 PHARMACISTS, NURSES, HOME HEALTH
CARE
 DRUG, BSC MANUFACTURERS
 RESEARCHERS
CURRENT NIOSH ACTIVITIES

OCCUPATIONAL EXPOSURE STUDY OF
HEALTHCARE WORKERS
 3-4
Institutions
 Pharmacy
 Minimum
 Several
and nursing personnel
50 exposed/50 non-exposed
environmental and biological endpoints
CURRENT NIOSH ACTIVITIES

VIAL CONTAMINATION STUDY
 4-6
Drugs
 Wipe outside of vials
 Determine extent of contamination of vials
Thomas H. Connor, Ph.D.
OCCUPATIONAL EXPOSURE
RELATED TO
ANTINEOPLASTIC AGENTS
http://www.uth.tmc.edu/schools/sph/an_agents