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Published on 1 November 2006

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Safe handling of cytotoxic drugs

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Maria Hedmer
PhD
Industrial Hygienist
Occupational and Environmental Medicine
Lund University Hospital
Sweden
E:maria.hedmer@med.lu.se

Cytotoxic drugs are a heterogeneous group of drugs inhibiting or preventing cell function. Cytotoxic drugs are frequently used in the medical treatment of different diseases such as cancer or rheumatoid arthritis. The use of cytotoxic drugs and the range of their applications in ­medical care have both increased over the past decade.(1) Doses have also increased. Many cytotoxic drugs are classified as mutagenic, carcinogenic or teratogenic to humans by the International Agency for Research on Cancer (IARC).

Cytotoxic drugs can be absorbed through several exposure routes, with occupational exposure absorption mainly occurring through the skin or through inhalation of gases or particles. Healthcare ­workers, including pharmacy, nursing and cleaning staff, have a potential risk of becoming occupationally exposed during their daily duties, and their health may be affected. Acute health effects such as hair loss, skin rash and light-headedness have been reported by workers handling cytotoxic drugs.(2–4) Exposure to cytotoxic drugs may also have delayed adverse health effects. Occupational exposure to cytotoxic drugs may involve a risk of reproduction effects such as infertility, spontaneous abortions and stillbirths.(5–10) Many cytotoxic drugs are ­carcinogenic to humans, and prolonged or high exposure to these drugs can increase the risk of genetic damages, which could initiate tumours. Several studies have reported genotoxic effects such as increased ­chromosomal aberrations(11,12) and increased levels of DNA strand breaks(13,14) in healthcare workers occupationally exposed to cytotoxic drugs. Since cytotoxic drugs must be handled for medical care, the risks for healthcare workers must be minimised. This can be achieved by the use of, for example, adequate protective clothing and other safety precautions.

Discussion
Occupational exposure may occur during the preparation or administration of infusion mixtures. In the literature, much attention has been paid to workers involved in the preparation and administration of cytotoxic drugs. However, recent studies have shown that staff such as assistant nurses and cleaning staff can come into direct contact with treated patients’ excreta such as urine, sweat and faeces.(15,16) They can be exposed to high concentrations of cytotoxic drugs during the nursing of treated patients or during the cleaning of toilets in hospital wards if they do not use adequate protective clothing. Dermal contamination of cytotoxic drugs was found in nursing, cleaning and pharmacy staff.(15) It is therefore important for healthcare workers to use personal protective clothing in connection with handling of cytotoxic drugs, nursing and cleaning, to avoid dermal uptake of these drugs. A long-sleeved protective gown should be used.

Protective gowns should only be used in premises where cytotoxic drugs are handled, due to the risk of spreading contamination of cytotoxic drugs. In addition, special protective gloves made of  latex or nitrile should be used. Two pairs of gloves made of ­different materials give extra protection. To obtain good protection, gloves can be changed after 30 minutes or immediately when spillage of cytotoxic drugs on the gloves has occurred. More protective clothing is probably needed due to the need for aseptic preparation of these drugs, but surgical masks do not protect the workers from exposure to cytotoxic drugs.

To avoid inhalation exposure in connection with the preparation of cytotoxic drugs, it is important to use biological safety cabinets with vertical laminar airflow and separate exhaust air. All handling of cytotoxic drugs should be done in as closed systems as possible to avoid emission of gases and particles into the air. The handling of the excreta of treated patient (eg, weighing of urine) should be performed in closed containers. Waste contaminated with cytotoxic drugs should be handled in as closed systems as possible.

Furthermore, is it essential that all workers who handle cytotoxic drugs or work in environments where cytotoxic drugs are handled are educated and trained so that they have the requisite knowledge of the risks involved and how to prevent them. It is also important that written safety and handling regulations are established.

By monitoring occupational exposure to cytotoxic drugs, risks can also be minimised. Methods to assess personal exposure to cytotoxic drugs and measure contamination levels in the workplace are available.(16) These methods can advantageously be used to investigate the actual or potential exposure to cytotoxic drugs. Wipe sampling of surfaces can be used to study the contamination levels on surfaces in the workplace and, thereby, working practices. It is also possible to perform personal or stationary air sampling of particles and gas. Personal exposure can be assessed by biological monitoring, since there is more than one exposure route and because personal protective equipment is used. A commonly used cytotoxic drug, cyclophosphamide, has been ­considered as an indicator for occupational exposure to cytotoxic drugs. By measuring its biomarker in urine samples, a measure of the internal dose can be estimated. However, the biomarker only reflects short-term exposure.

Conclusion
It is important that pharmacy staff and nurses, as well as assistant nurses and cleaning staff, use protective clothing and gloves to avoid skin uptake of cytotoxic drugs. Uptake via inhalation can be avoided by using biological safety cabinets, closed systems and ­containers.

Combined with education, regulations and the possibility to perform exposure measurements and biological monitoring, cytotoxic drugs can be handled safely in medical care, thereby minimising the risks for healthcare workers.

Reference

  1. Connor TH, Sessink PJ, Harrison BR, et al. Surface contamination of chemotherapy drug vials and evaluation of new vial-cleaning techniques: results of three studies. Am J Health-Syst Pharm 2005;62:475-84.
  2. Krstev S, Perunicic B, Vidakovic A. Work practice and some adverse health effects in nurses handling ­antineoplastic drugs. Med Lav 2003;94:432-9.
  3. Valanis BG, Vollmer WM,Labuhn KT, Glass AG. Association of antineoplastic drug handling with acute adverse effects in pharmacy personnel. Am J Hosp Pharm 1993;50:455-62.
  4. Valanis BG, Vollmer WM,Labuhn KT, Glass AG. Acute symptoms associated with ­antineoplastic drug handling among nurses. Cancer Nurs 1993;16:288-95.
  5. Selevan SG, Lindbohm ML,Horung RW, Hemminki K. A study of occupational exposure to antineoplastic drugs and fetal loss in nurses.N Engl J Med 1985;313:1173-8.
  6. Stucker I, Caillard JF, Collin R, et al. Risk of spontaneous abortion among nurses handling antineoplastic drugs. Scand J Work Environ Health 1990;16:102-7.
  7. Valanis B, Vollmer W,Labuhn K, Glass A. Occupational exposure to antineoplastic agents and self-reported infertility among nurses and pharmacists. J Occup Environ Med 1997;39:574-80.
  8. Valanis B, Vollmer WM, Steele P.Occupational exposure to ­antineoplastic agents: self-reported miscarriages and stillbirths among nurses and pharmacists.J Occup Environ Med 1999;41:632-8.
  9. Dranitsaris G, Johnston M,Poirier S, et al. Are health care providers who work with cancer drugs at an increased risk for toxic events?A systematic review and meta-analysis of the literature.J Oncol Pharm Pract 2005;11:69-78.
  10. Fransman W, Peelen S,Roeleveld N, et al. Relationship between quantitative estimates of dermal exposure to antineoplastic drugs and reproduction toxic effects among nurses. IOHA 6th International scientific conference. Pilanesberg, South Africa, 2005a;E2-2, p. 96.
  11. Burgaz S, Karahalil B, Canhi Z,et al. Assessment of genotoxic damage in nurses occupationally exposed to antineoplastics by the analysis of chromosomal aberrations.Hum Exp Toxicol 2002;21:129-35.
  12. Cavallo D, Ursini CL, Perniconi B, et al. Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees.Mutat Res 2005;587:45-51.
  13. Fuchs J, Hengstler JG, Jung D,et al. DNA damage in nurses handling antineoplastic agents.Mutat Res 1995;342:17-23.
  14. Undeger U, Basaran N, Kars A, Guc D. Assessment of DNA damage in nurses handling antineoplastic drugs by the alkaline COMET assay.Mutat Res 1999;439:277-85.
  15. Fransman W, Vermeulen R, Kromhout H. Dermal exposure to cyclophosphamide in hospitals during preparation, nursing and cleaning activities. Int Arch Occup Environ Health 2005;78:403-12.
  16. Hedmer M. Monitoring of occupational exposure to antineoplastic drugs. Faculty of Medicine Doctoral Dissertation Series 2006:56. Lund University: Sweden; 2006.


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