EXPOSURE TO ANTINEOPLASTIC AGENTS IN THE PHARMACY LABORATORY SETTING AND ONGOING NIOSH STUDIES

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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 tmc6_at_cdc.gov

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EXAMPLES OF HAZARDOUS DRUGS

• Antineoplastic agents
• Antiviral agents
• Hormonal agents
• Immunosuppressant agents
• Some antibiotics

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DEFINITION OF HAZARDOUS DRUGS

• Carcinogenicity
• Teratogenicity/developmental toxicity
• Reproductive toxicity
• Organ toxicity at low doses
• Genotoxicity
• Structure/activity similar to known hazardous drug

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ANTINEOPLASTIC AGENTS

• RECENT CONCERNS
• More cancer patients
• More combinations of drugs
• Higher doses of drugs
• More potent drugs
• New procedures/settings

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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

• Workers in manufacturing
• Pharmacists and technicians
• Nursing personnel
• Physicians
• Operating room personnel
• Housekeeping and laundry personnel
• Veterinarians
• Retail pharmacists

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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

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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

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COMMON SOURCES OF EXPOSURE

• 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

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SURFACE CONTAMINATION STUDY

• 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)

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DRUG RECONSTITUTION WITH NEEDLE AND SYRINGE

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DRUG TRANSFER WITH NEEDLE AND SYRINGE
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OTHER SOURCES OF EXPOSURE

• 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

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FLOOR CONTAMINATION FROM CYCLOPHOSPHAMIDE SPILL
NG/CM2
DAYS
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OCCUPATIONAL MONITORING

• WIPE SAMPLES
• Since 1992, 13 studies reported in literature
• AIR SAMPLES
• Since 1983, 12 studies reported in literature

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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

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OCCUPATIONAL MONITORING

• WIPE SAMPLES
• Drugs that are commonly used for wipe sample
  studies
• Cyclophosphamide
• Ifosfamide
• Fluorouracil
• Methotrexate

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OCCUPATIONAL MONITORING

• WIPE SAMPLES
• Locations that have been sampled
• Pharmacy and Preparation areas
• Treatment Areas
• Adjacent Areas

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OCCUPATIONAL MONITORING

• AIR SAMPLING
• Drugs that are commonly used for air sampling
• Cyclophosphamide
• Ifosfamide
• Fluorouracil

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OCCUPATIONAL MONITORING

• AIR SAMPLING
• Air 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

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OCCUPATIONAL MONITORING

• URINE ANALYSIS FOR SELECTED DRUGS
• Most studies have been performed in Europe
• In 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

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OCCUPATIONAL MONITORING

• URINE ANALYSIS FOR SELECTED DRUGS
• Approximately 100 individuals/3years
• 14 German hospitals
• Cyclophosphamide 40
• Ifosfamide 14
• Anthracyclines 4.5
• Pethran et al, Int Arch Occup Environ Health
  (2003)

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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)

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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

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CURRENT NIOSH ACTIVITIES

• PERSONAL PROTECTIVE EQUIPMENT STUDY
• ASTM Standard for Chemotherapy Gloves
• Four drugs
• Several types of glove/gown materials

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CURRENT NIOSH ACTIVITIES

• NIOSH ALERT ON HAZARDOUS DRUGS
• All hazardous drugs
• Focus on antineoplastic drugs
• Release expected summer, 2003

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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

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CURRENT NIOSH ACTIVITIES

• OCCUPATIONAL EXPOSURE STUDY OF
• HEALTHCARE WORKERS
• 3-4 Institutions
• Pharmacy and nursing personnel
• Minimum 50 exposed/50 non-exposed
• Several environmental and biological endpoints

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CURRENT NIOSH ACTIVITIES

• VIAL CONTAMINATION STUDY
• 4-6 Drugs
• Wipe outside of vials
• Determine extent of contamination of vials

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Thomas H. Connor, Ph.D.

• OCCUPATIONAL EXPOSURE RELATED TO
• ANTINEOPLASTIC AGENTS
• http//www.uth.tmc.edu/schools/sph/an_agents