1. 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@cdc.gov

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

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

4. 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

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

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

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

8. 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

9. WORKER PROTECTION l 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

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

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

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

13. DRUG RECONSTITUTION WITH NEEDLE AND SYRINGE

14. DRUG TRANSFER WITH NEEDLE AND SYRINGE

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

16. FLOOR CONTAMINATION FROM CYCLOPHOSPHAMIDE SPILL DAYS NG/CM 2

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

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

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

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

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

22. OCCUPATIONAL MONITORING l AIR SAMPLING n Air 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

23. OCCUPATIONAL MONITORING l URINE ANALYSIS FOR SELECTED DRUGS n Most studies have been performed in Europe n In 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

24. OCCUPATIONAL MONITORING l URINE ANALYSIS FOR SELECTED DRUGS n Approximately 100 individuals/3years n 14 German hospitals n Cyclophosphamide 40% n Ifosfamide 14% n Anthracyclines 4.5% Pethran et al, Int Arch Occup Environ Health (2003)

25. 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)

26. 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

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

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

29. 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

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

31. CURRENT NIOSH ACTIVITIES l VIAL CONTAMINATION STUDY n 4-6 Drugs n Wipe outside of vials n Determine extent of contamination of vials

32. Thomas H. Connor, Ph.D. OCCUPATIONAL EXPOSURE RELATED TO ANTINEOPLASTIC AGENTS http://www.uth.tmc.edu/schools/sph/an_agents