It is vital that prior to working in an environment that handles hazardous drugs, everyone understands the risks associated and how to minimise them. Whilst protocols and procedures can be compiled and established, it is important that everyone is aware of their importance. There are numerous resources, research articles, studies and guidelines that have been published regarding this subject.
A hazardous drug may display the traits of carcinogenicity, organ toxicity at low doses, genotoxicity, teratogenicity, and reproductive toxicity. These drugs are used in a variety of healthcare settings to treat cancer and other conditions such as rheumatoid arthritis, multiple sclerosis and auto-immune disorders. Often cytotoxic drugs have a purple sticker on them that displays a cell in late telophase (Figure 1) as a prompt to handle them according to Society of Hospital Pharmacists of Australia (SHPA), Australian and State guidelines.
Figure 1. Cytotoxic drug symbol.
Until further research and information becomes available it is probably advisable to adhere to the same guidelines when handling Monoclonal Antibodies (MABs), Bacillus of Calmette and Guerin (BCG), and tyrosine kinase receptor inhibitors.
There are many scenarios and a wide spectrum of people that can be at risk of occupational exposure to these medications (and related waste), particularly when:
- Preparing drugs
- Administering drugs
- Transporting drugs
- Storing drugs
- Handling patient waste
- Transporting and disposing of waste
- Cleaning up spills
Exposure can happen through skin contact, skin absorption, inhalation of aerosols/drug particles, ingestion, and sharps injuries. There have been a number of studies to determine the effects of occupational exposure to these drugs. Anderson7 detected mutagens in the urine of pharmacist’s working with cytotoxic drugs. Substantial amendments were then made to lessen exposure and risk to operators such as the use of Cytotoxic Drug Safety Cabinets or Pharmaceutical Isolator Cabinets to replace the older Laminar Airflow Cabinets which propel air towards the operator, possibly contaminated with the drug.
In 1984, Chrysostomou8 found a link between the duration of exposure to cytotoxic drugs and mutation frequency in oncology staff. In 1983, deWerk Neal10 monitored the general air of 10 hospital clinics and determined that fluorouracil and cyclophosphamide were being breathed by operators. This study highlighted the risk to staff of exposure to airborne cytotoxic aerosols under normal conditions – unless further special precautions are undertaken. More recently, Fransman11 demonstrated that traces of cyclophosphamide were present on the foreheads, hands and forearms of; pharmacy technicians, cleaning personnel, and nurses that handled the drug whilst carrying out their normal duties. Worksafe Victoria4 continuously emphasise that where a high standard of risk control is in place and adhered to, the effects upon the operator’s health is reduced.
Of particular importance is the exposure of anti-neoplastic drugs to pregnant women and those of reproductive age. Selevan9 in 1985 showed an association between exposure to cytotoxic drugs (particularly cyclosphosphamide, doxorubicin and vincristine) and foetal loss in nurses that were exposed during their first trimester. Fransman12 showed that nurses exposed to
anti-neoplastic drugs took longer to conceive, had a lower birth rate, and that there was a greater incidence of premature birth.
On the basis of these and other findings, the significance of adhering to the relevant standards and guidelines is highlighted. Worksafe Victoria advise that employers and staff who handle these hazardous drugs have an obligation to:
- Work to a risk management strategy
- Keep up-to-date with current practices and standards
- Consult with employees at key stages of risk strategy development i.e. the planning stage, during implementation, monitoring and review
- Assess policies and procedures on a regular basis
Only those employees that attain the required level of training and proficiency should be allowed to handle hazardous materials. The level of training depends on the staff member and potential for contact, as listed in Table 1.
Table 1. Risk Assessment of Personnel that may be exposed to Hazardous Drugs.
|High Risk||Low Risk|
|Pharmacy Technicians/Operators||Supervisors and managers||Couriers|
|Oncology Pharmacists||Maintenance personnel||Waste handlers|
|Nursing and medical personnel||Stores personnel||Carers|
|Laboratory staff members||Cleaners||Ambulance Officers|
|Animal handlers (research)||On-site waste transporters||Patient transport personnel|
Staff health is of paramount importance and so guidelines specify the required screening to identify if there are any changes due to occupational exposure to a hazardous substance.
Full blood and lipids should be tested at baseline for all staff that are assessed as being at ‘high risk’.
Most cytotoxic tablets and capsules are in blister packs, so generally the pharmacist will not need to take extra precautions when dispensing. However, when handling loose tablets (e.g. methotrexate) or when administering medications to patients, the nurses, carer, or pharmacist should always:
- Wear gloves
- Use separate counting trays from those used for non-cytotoxic medications
- Use separate, disposable counting spatulas
- Clean and rinse equipment properly after use
- Ensure tablets are not crushed or broken
A number of studies have evaluated various deactivating and decontaminating agents for use on surfaces contaminated with cytotoxic drugs. There are a number of factors to consider when selecting the most appropriate cleaning agent. Best practice would be to investigate exactly what to use before handling each drug (generally in the consumer medication information [CMI] leaflet). International standards recommend ‘wipe sampling’ of the surfaces before and after cleaning the most commonly used cytotoxic agents.
Investigation of lipophilic drugs, e.g. carmustine and paclitaxel can be done to ascertain that cleaning procedures are effective. Sodium hypochlorite (bleach) is the most efficient reagent to chemically degrade many cytotoxic drugs, and is often used, however, it is not effective with all cytotoxic drugs, e.g. dicarbozide and carmustine (under certain conditions). Alkaline cleaning agents (e.g. Decon-90 or Extran), 70% sterile alcohol and sterile water, either alone or in combination, also appear in the literature.
The agent used should be validated for the particular cytotoxic drug(s) that are/is present and for the surface on which it is being used. Particular attention is necessary to ensure that the cleaning agent used does not degrade the cytotoxic drug into other toxic components.
The purpose of this article is to thus highlight the importance of adhering to guidelines and standards. It is also for readers to gain an insight and an appreciation into the thought and research that has been compiled towards making the handling of hazardous drugs safer.
- SHPA Committee of Specialty Practice in Oncology. Standards of Practice for the Safe Handling of Cytotoxic Drugs in Pharmacy Departments. J Pharm Pract Res 2005; 35(1); 44–52.
- eviQ Cancer Treatments Online. Resource Document – Safe Handling and Waste Management of Hazardous Drugs V3. Eveleigh: Cancer Institute NSW; 2012. Available from www.eviq.org.au/Protocol/tabid/66/id/188/Default.aspx. Accessed 1 September 2012.
- eviQ Cancer Treatments Online. Hazardous Drugs Table V1. Eveleigh: Cancer Institute NSW; 2011. Available from www.eviq.org.au/Protocol/tabid/66/id/909/Default.aspx. Accessed 1 September 2012.
- Cytotoxic Drugs Working Party. Handling Cytotoxic Drugs in the Workplace. Melbourne: Worksafe Victoria; 2003.
- Cytotoxic Drugs Working Party. Cytotoxic Drugs and Related Waste Risk Management Guide. Gosford: Workcover NSW; 2008.
- eviQ Cancer Treatments Online. Health Effects Related to Occupational Exposure to Cytotoxic Drugs. Eveleigh: Cancer Institute NSW. Available from www.eviq.org.au/AdditionalClinicalInformation/tabid/64/id/255/Default.aspx. Accessed 1 September 2012.
- Anderson RW, Puckett WH, Dana WJ, Nguyen TV, Theiss JC, Matney TS. Risk of handling injectable antineoplastic agents. Am J Hosp Pharm 1982; 39: 1881–1887.
- Chrysostomou A, Seshadri R, Morley AA. Mutation frequency in nurses and pharmacists working with cytotoxic drugs. Aust N Z J Med 1984; 14: 831–834.
- Selevan SG, Lindbohm ML, Hornung RW, Hemminki K. A study of Occupational Exposure to Antineoplastic Drugs and Fetal Loss in Nurses. N.Engl. J Med 1985; 313: 1173–1178.
- deWerk Neal A, Wadden RA, Chiou WL. Exposure of hospital workers to airborne antineoplastic agents. Am J Hosp Pharm 1983; 40: 597–601.
- 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: 403–412.
- Fransman W, Roeleveld N, Peelen S, de Kort W, Kromhout H, Heederik D. Nurses with Dermal Exposure to Antineoplastic Drugs: Reproductive Outcomes. Epidemiology 2007; 18: 112–119.