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Educating healthcare workers about the risks associated with handling cytotoxic drugs not only protects the workers themselves but also helps decrease the number of samples contaminated, consequently improving the quality of practices
Claude Dussart
PharmD PhD
Military teaching hospital
Desgenettes
Hospital Pharmacy
Lyon, France
Bertrand Favier
PharmD PhD
Centre Leon Berard
Regional Cancer Centre
Hospital Pharmacy
Lyon, France
Cytotoxic medications are therapeutic agents intended for, but not limited to, the treatment of cancer.
Cytotoxic drugs, sometimes known as anti-neoplastic, anti-cancer or cancer chemotherapy drugs, include a wide range of chemical compounds. These medications are known to be highly toxic to cells, mainly through their action on cell reproduction. Because of their ability to kill tumour cells by interfering with cell division, they are extensively used to treat cancer and some have other medical applications.
Cytotoxic drugs are commonly administered by injection of single doses or by continuous infusion. Some are given orally in tablet, capsule or liquid form.
Most of the evidence on health effects is based on data from patients given therapeutic doses, but people handling such drugs need to be aware that some of these compounds are mutagenic and carcinogenic. The potential for exposure exists during various tasks eg, drug reconstitution and mixing, connecting and disconnecting intravenous tubing, and disposing of waste equipment or patient waste. Employers need to make sure that employees are aware of the risks and agreed control measures are being maintained.
The pharmacist ensures that cytotoxic drug products are prepared in a way that maximises product quality, and that cytotoxic drugs and related waste are handled in accordance with documented procedures that ensure the safety of personnel and the environment.
Procedures are designed to reduce the number of
opportunities for unnecessary contact with cytotoxic
agents by hospital personnel and to prevent contamination
of the hospital environment and staff with cytotoxic
agents.
The primary focus of safety during the use of cytotoxic
drugs must be on:
- Control of the working environment.
- Safe work practices.
- Education and training of personnel.
Safe preparation of cytotoxic drugs
The work area should be clearly designated for drug preparation and access restricted to authorised staff.
Material
Cytotoxic drug safety cabinet (with high efficiency particulate air filtration) is defined as the primary barrier against exposure to aerosols that are produced in the preparation, manipulation and dispensing of cytotoxic drugs. It is a key control measure in preventing employee exposure to cytotoxic drugs, many of which are classified as hazardous to health and may also be carcinogens. It also has to protect the product from microbiological contamination during drug reconstitution.
The work surface of the safety cabinet should be covered with plastic-backed absorbent paper. This will reduce the potential for dispersion of droplets and spills and facilitate cleanup. This paper should be changed after any overt spill and at the end of each work shift.
Cleanrooms, cytotoxic laminar flow drug safety cabinets and other specially designed equipment should be in place and maintained in accordance with the appropriate standards and practice to facilitate the safe preparation of cytotoxic medications.
Ready-to-use, parenteral cytotoxic drugs may be presented as pre-filled Luer lock syringes or as infusions. The immediate container of a ready-to-use, cytotoxic dosage form should be sealed. If the immediate container were to break, the outer packaging should contain any spillage.
Totally enclosed systems should be used to control exposure to carcinogenic compounds. Where this cannot be achieved, engineering controls, processes or systems of work should be designed and operated to minimise the generation of, and to suppress and contain, carcinogenic compounds – eg, by partial enclosure of processes and handling systems, appropriate
local exhaust ventilation and general ventilation.
Personal protective equipment
The following personal protective equipment is recommended
during the handling, administration and disposal
of cytotoxic substances:
- Latex Gloves-no powder, double gloved (changed at regular intervals or after contamination is apparent or perforation occurs).
- Protective disposable gown.
– Lint free, low permeability.
– Closed footwear.
– Closed front, long sleeves, elastic/knit closed
cuffs.
– Cuffs tucked under gloves.
– Goggles or protective glasses with side-shields.
– Wear only in preparation area.
- Respiratory protection (respiratory protective device where inhalation risk exists eg, cytotoxic spill)
Transport
Containers used for transporting cytotoxic medications
should be hard-walled and robust, securely closed and
labelled with cytotoxic warnings.
The outer packaging should be impervious to accidental spills. Once heat-sealed, the cytotoxic drug product should be placed in a hard-walled container (made from foam or other suitable material), appropriately labelled and dedicated to this purpose.
Storage
All stocks of cytotoxic drugs should be kept in a secure area, with access limited to specified authorised personnel. Cytotoxic medications should be stored in a hard-walled and robust container, securely closed and labelled with cytotoxic warnings. Refrigeration may be necessary.
Personnel contamination
The main routes of exposure to cytotoxic drugs are through the inhalation of the drug dusts or aerosols, skin absorption, inadvertent ingestion through contact with contaminated food or cigarettes, and needle stick injuries. Opportunities for exposure can occur during preparation and administration of the drugs, handling of body fluids from patients receiving cytotoxic drugs, handling and disposal of cytotoxic wastes and related trace contaminated material and transportation of cytotoxic drugs.
Overt contamination of gloves or gowns, or direct skin or eye contact should be treated as follows:
- Immediate removal of the gloves or gown.
- Wash the affected skin area immediately with soap (not germicidal cleaner) and water.
- For eye exposure, immediately flood the affected eye with water or;
- isotonic eyewash designated for that purpose for at least 15 minutes.
- Obtain medical attention immediately.l Obtain medical attention immediately.
The risks to workers handling cytotoxic drugs are a combined result of the drugs’ inherent toxicity and the extent to which workers are directly exposed. Other factors include the susceptibility of the individual to the drugs’ toxic effects, and co-factors such as dietary habits, smoking, and man-made or natural environmental contaminants.
Education
All personnel (pharmacists, technicians, delivery people, storemen, etc) involved in handling cytotoxic drugs should be informed of the potential hazards associated with handling such drugs; the special precautions to be taken when handling cytotoxic drugs and cytotoxic waste; and the actions to be taken in the event of a cytotoxic spill and/or contamination.
All staff working with chemotherapy drugs must be well-trained and must demonstrate competency in the accurate and safe preparation of hazardous drugs. Employers should ensure that only employees who have received appropriate training and have obtained the required level of proficiency, handle cytotoxic medications and waste.
Employers need to ensure that employees handling cytotoxic drugs are given suitable and sufficient information, instruction and training that is relevant to their work.
Training and regular evaluation of technicians involved in the preparation of anti-neoplastic agents seems essential to reduce occupational exposure. In this way, a continuous training program was established in a French military techning hospital (Lyon-France). Technicians were asked to prepare a safe simulated liquid cytotoxic drug with a fluorescein solution (10mg/L). After, occupational exposure with this solution was simulated. Ultra-violet light (365nm) was employed to determine surface contamination. This continuous training program is tested and validated with pharmacy technicians. All people handling these drugs (physicians, nurses, pharmacy staff) can use this program. Short mandatory training courses are stimulating and well appreciated.
Health evaluation and monitoring
A variety of methods have been used to investigate potential effects of exposure to cytotoxic drugs. The workplace can be monitored using environmental measurements. Exposure can also be assessed by biological monitoring-measuring concentrations of cytotoxic drugs or their metabolites in body fluids, usually urine.
Appropriate engineering controls should be in place to protect the drug product from microbial contamination and to protect personnel and the environment from the potential hazards of the product. These engineering controls should be maintained according to applicable regulations and standards.
Special precautions
Health professionals who are pregnant or breastfeeding or are planning to become imminently pregnant or on immunosuppressive therapy should not handle cytotoxic substances.
Conclusion
Despite the publication of guidelines for handling antineoplastic agents, measurable amounts of these drugs are still found at various hospital sites. In this context, the French cancer network ONCORA supported the present study to assess the impact of environmental contamination controls on the quality of practices during the preparation of cytotoxic drugs.
The first part of the study was conducted at 5 voluntary
hospitals. A total of 65 wipe samples of objects
and surfaces were taken in the drug preparation rooms
and analysed for the presence of 5-fluorouracil (5FU).
Measurable amounts of 5FU were detected in 21 samples
(32%). Many surfaces within Biological Safety
Cabinets and isolators were found contaminated
(36%). The worst results were obtained on gloves and
on the outside of infusion bags. The same method was
applied during the second part of the study, conducted
6 months after the end of the first audit. Global contamination
was reduced to 17%.
This study shows that appropriate handling helps decrease the number of samples contaminated, making it possible to recommend these controls for evaluating and improving the quality of practices. Since 2007, the network’s laboratory has extended its activities to all French hospitals interested in this quality assurance programme.
References
1. Association of Scottish Trust Chief Pharmacists.
Guidelines for the safe use of cytotoxic chemotherapy
in the clinical environment. (http://www.sehd.scot.nhs.
uk/mels/ HDL2001_13_report.pdf)
2. American Society of Health-System Pharmacists.
ASHP guidelines on preventing medication errors with
antineoplastic medications. Am J Health-Syst Pharm
2002;59:1648—68.
3. Dussart C, Favier B, et al. Bull Cancer 2008;95(9):821—2.
4. Gilles L, Favier B, et al. Bull Cancer 2009;96(9):839—49.
5. SHPA Committee of Specialty Practice in Oncology. Standards of practice for the safe handling of cytotoxic drugs in pharmacy departments. Journal of Pharmacy Practice and Research 2005;35 (1): 44—52.
6. Tolar MH, Power LA, et al. Am J Hosp Pharm
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