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

THOMAS H. CONNOR, Ph.D.Senior Service FellowNational Institute for

Occupational Safety and HealthCincinnati, OH

513-533-8399 tmc6@cdc.gov

EXAMPLES OF HAZARDOUS DRUGS

Antineoplastic agents

Antiviral agents

Hormonal agents

Immunosuppressant agents

Some antibiotics

DEFINITION OF HAZARDOUS DRUGS

Carcinogenicity Teratogenicity/developmental toxicity Reproductive 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

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

POTENTIALLY EXPOSED GROUPS

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

ROUTES OF EXPOSURE

INHALATION Droplets/particulates Vapors

DERMAL

ORAL

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

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)

DRUG RECONSTITUTION WITH NEEDLE AND SYRINGE

DRUG TRANSFER WITH NEEDLE AND SYRINGE

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

FLOOR CONTAMINATION FROM CYCLOPHOSPHAMIDE SPILL

0

10

20

30

40

50

60

70

80

0 28 56 84 112 140 168

DAYS

NG/CM2

OCCUPATIONAL MONITORING

WIPE SAMPLES Since 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 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

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

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)

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 Standard for Chemotherapy Gloves

Four 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 and nursing personnel

Minimum 50 exposed/50 non-exposed

Several 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