US Pharm. 2014;39(8)(Pharm&Tech suppl):4-7.
Healthcare workers are being exposed to hazardous drugs during preparation and administration of chemotherapy. This has been an ongoing concern for years in the healthcare industry. Various studies showing contamination in the preparation area, long-term chromosomal abnormalities, biologic marker changes in workers, long-term effects on reproduction, hair loss, rashes, miscarriages, birth defects, and cancers due to chemotherapy exposure make this concern legitimate.1 There are guidelines for safe handling of both IV and oral chemotherapy from the American Society of Health-System Pharmacists (ASHP), the Oncology Nursing Society (ONS), and the Occupational Safety and Health Administration (OSHA), all of which discuss how to prepare, handle, and administer chemotherapy safely.1-3
The National Institute for Occupational Safety and Health (NIOSH) guidelines for IV chemotherapy were updated in 2004 (safe handling of hazardous drugs guidelines have been promoted since the mid-1980s).4 The update included the use of closed-system transfer devices (CSTDs) based on various studies, which showed chromosomal abnormalities and cancers developing in workers years after exposure. This change was made as a result of many studies that were conducted and revealed a need for a CSTD.
One study funded by NIOSH looked at pharmacy and nursing personnel to provide more evidence for the risks healthcare workers face when preparing, administering, dispensing, and/or transporting chemotherapy.5 One of the purposes of the study was to investigate specific chromosomal changes that occur in healthcare workers and their level of the exposure. It was found that pharmacy staff had twice as many chromosomal abnormalities as nursing staff, as pharmacists have much more exposure. The most common chemotherapy agents healthcare workers were exposed to were alkylating agents, with the most frequent chromosomal abnormalities occurring in chromosomes 5 and 7, which are associated with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The outcome of this study showed that facilities should maintain proper clean rooms, pass-through hatches, and personal protective equipment, and should utilize CSTDs.5
Another cross-sectional study looked at pharmacy and nursing personnel over a 6-week period to document exposure to chemotherapy by analysis of urine and blood samples.6 Comparing exposed and unexposed workers, researchers found that cyclophosphamide and 5-fluorouracil were the most commonly detected drugs in the urine and blood samples of healthcare workers. This study concluded that although facilities follow recommendations of safe-handling practices, healthcare workers are still not protected and end up with contamination by antineoplastic drugs.6 This only confirms and supports the need for a CSTD.
Role of CSTDs: Although CSTDs do not guarantee 100% protection, they provide significantly more of it than without them. Many studies have been done to evaluate the use of a CSTD. These studies include assessing fluid and vapor leakage during preparation and administration, the impact of CSTDs on environmental contamination and personnel exposure, and the impact of CSTDs on workflow and staffing.1 A closed system is defined by NIOSH as “a device that does not exchange unfiltered air or contaminants with the adjacent environment for the use in compounding and administering sterile doses of chemotherapy and other hazardous drugs” and “a drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drugs or vapor concentrations outside the system.”1,3
A certified CSTD should be able to perform standard functions needed to make chemotherapy, such as injecting and disengaging the syringe from the vial through the closed septum and the bag, spiking the bag and priming the IV set, and transferring by such means as disengaging secondary sets from the primary set or administering an IV push dose from a syringe into a Y-site.1 There are several FDA-approved CSTDs available in the United States: ChemoClave (ICU Medical), BD PhaSeal CSTD (Becton, Dickinson and Company), OnGuard (B. Braun Medical), and EquaShield CSTD (EquaShield Medical).1,4
When an institution is selecting a CSTD, several factors should be considered: ease of use, cost, safety and efficacy data, training modules, and comfort level of pharmacists, physicians, and nurses. In addition to using CSTDs, all personnel should follow current handling guidelines, which state that when preparing hazardous drugs, they should wear and use a long-sleeved, distinctively colored gown with closed cuffs, a closed-front hood in a biological safety cabinet (BSC) with vertical flow, gloves with a distinctive color put over long sleeves (change every 30 minutes), and eye protection if splashing is possible.4 One study conducted in U.S. hospital pharmacies showed that preparing chemotherapy with a CSTD resulted in significantly reduced levels of contamination by certain chemotherapy agents.4
When an employee is being trained for use of any CSTD, he or she should be observed extremely closely, as consistency and proper use are highly necessary for chemotherapy. Physicians and especially nursing personnel are also very closely involved with administering chemotherapy and need to be properly trained.7 In conclusion, the use of a CSTD in conjunction with personal protective equipment has been proven to increase safety levels when preparing, transporting, administering, and disposing of hazardous drugs.4
The use of oral chemotherapy has risen, accounting for 25% of new chemotherapy agents. This increase in prevalence has forced healthcare workers, especially pharmacists, to learn more about the safe handling of these agents. Handling of oral chemotherapy can affect all types of pharmacies, whether retail, hospital, or specialty, and even a physician’s office. Oral chemotherapy can have just as many effects on healthcare workers for long-term exposure as IV chemotherapy, but most people do not realize it. Unfortunately, this has been a challenge, since there are no well-established guidelines on handling oral chemotherapy as there are for IV chemotherapy agents because they are still evolving, and similar precautions need to be taken.7 The general misconception is that since oral chemotherapy provides ease of administration, the exposure risk is low and the necessary precautions are minimal.8
There are potentially harmful risks from handling oral chemotherapy just as there are for IV chemotherapy. Chemotherapy agents often have a narrow therapeutic index (NTI) and are frequently given in combination, which increases adverse effects and exposure risks.7,8 Some of these effects can be minor, such as headache, dizziness, mucosal sores, contact dermatitis, minor hair loss, and tissue injury; but others can be more severe and long-term, such as infertility, miscarriage, leukemia, and congenital malformations.8
Exposure to chemotherapy can occur at any point—during transporting, packaging, administering, dispensing, unpacking, or disposal. When oral chemotherapy agents are stored, they should have their own designated area in the pharmacy, and special instructions should be followed if necessary (e.g., protect from light).8 Some of the risks of exposure to oral chemotherapy for healthcare workers depend on the formulation of the medication (i.e., uncoated vs. coated tablets). Uncoated tablets can pose a risk of exposure via inhalation or contact with the skin. Coated tablets may offer less of a risk since they cannot be crushed or split. When handling oral chemotherapy, always do so carefully whatever the type of pharmacy; the same applies if it takes place at a patient’s home.
All patients should be advised by pharmacists to handle oral chemotherapy agents with protective equipment. Healthcare workers should always wear two pairs of gloves approved by the American Society for Testing and Materials International (ASTM)—not all gloves are ASTM-approved. The same handwashing procedures used with IV chemotherapy should be followed (i.e., wash hands before putting on and after taking off the gloves).
A study by Fransman et al was conducted to determine the potential dermal exposure to oral cyclophosphamide in a hospital.9-11 It was found that there was significant contamination on and around the toilet.
If a healthcare worker needs to count, crush, or break an oral chemotherapy tablet or capsule, then a separate counting tray labeled “For chemotherapy use only” should be used (this may be substituted for a BSC since not all retail and specialty pharmacies may have one of these). Such trays should be cleaned using sterile water and gauze and a chemotherapy-rated detergent. This should be followed with a sodium hypochlorite solution and a neutralizer and another rinse. Any materials used to wipe the trays should be discarded and disposed of into a proper contamination waste bucket. Oral chemotherapy agents should never be placed in an automated dispensing machine or robot as this can compromise the integrity of the medication by accidentally crushing or cutting the dose. The damage would be extensive, as it would require that the machine be cleaned thoroughly and pose a risk to any healthcare workers who were exposed to the medication in the process or could cause cross-contamination with other medications.
All healthcare workers should be trained and attend some type of orientation for safe handling of oral chemotherapy.7,8 The pharmacist should counsel patients and their family members on proper handling of the chemotherapy medication, as this is an important duty and an opportunity for intervention. When labeling oral chemotherapy agents, pharmacists should avoid using vague directions such as “Use as directed,” and the exact count of medications with the start and stop date should be provided to the patient. Pharmacists should counsel patients to not leave their medication in an open area near water or sunlight and not to discard drugs down the toilet or in the garbage.8,12 TABLES 1 and 2 list specific recommendations for patients and their caregivers and are important guides to keep posted in the work area.8
Summary and Conclusion
In a March 2011 editorial in the Journal of Oncology Pharmacy Practice, the authors concluded that “if the different closed systems currently available are equally effective, then the choice comes down to cost and ease of use.”13 CSTDs are an annual expense, but the expense is outweighed by the ethical responsibility to protect the employees. While these systems provide an enhanced level of protection and mitigate the risk, technology is still evolving, and no commercially available CSTD at this time can claim 100% elimination of exposure to hazardous drugs. The reduction in exposure observed with CSTDs does not replace the need for good compounding procedures and proper cleaning.
Both IV and oral chemotherapy have special precautions that must be taken when preparing, administering, or dispensing these agents for the safety of patients and healthcare providers. It is essential to adequately train employees and assess their knowledge and comfort in the proper use of CSTDs. In 2004, NIOSH issued an alert stating, “Evidence documents a decrease in drug contaminants inside a Class II BSC when a CSTD is used and concluded that facilities should consider using devices such as CSTDs, glovebags, and needle-less systems when transferring hazardous drugs from the primary packaging (such as vials) to dosing equipment (such as infusion bags, bottles, or pumps).”1-3 Various studies have shown abnormalities in chromosomes 5 and 7 in healthcare workers—the same abnormalities found in cancer patients.14
In the past decade, the use of oral chemotherapeutic agents for the treatment of cancers has significantly increased. Oral chemotherapy is associated with many advantages, including ease of use and convenience for patients, a reduction in both time and costs associated with traveling to hospitals for IV chemotherapy infusions, and possible improvements in the quality of life of patients taking oral chemotherapy (as opposed to IV formulations).
While there are definite advantages to oral chemotherapy, many patients have the misconception that outpatient oral therapy is safer than inpatient IV therapy. Chemotherapeutic agents, regardless of formulation, are medications with NTIs. This simply implies that even a minuscule increase or decrease in the dose could be potentially hazardous to the patient. Additionally, chemotherapeutic agents are cytotoxic, meaning that when individuals who do not have cancer are exposed to these drugs, they are at a high risk for developing adverse events (including cancer itself) due to the cell-destroying properties of the chemotherapy. Because many chemotherapy regimens employ the use of oral agents, it is essential that patients, caretakers, and healthcare providers be educated on how to safely handle these medications to optimize therapy for the patient and reduce risk to all others who come into contact with these drugs.8-10
1. Power LA. Closed-system transfer devices for safe handling of injectable hazardous drugs. Pharm Pract News. June 2013; 1-16. www.pharmacypracticenews.com/download/CSTD_ppn0613_WM.pdf. Accessed July 2, 2014.
2. ASHP guidelines on handling hazardous drugs. Drug Distribution and Control: Preparation and Handling–Guidelines. 2004;95-114. www.ashp.org/doclibrary/bestpractices/prepgdlhazdrugs.aspx. Accessed July 2, 2014.
3. Neuss MN, Polovich M, McNiff K, et al. 2013 updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy admin-istration safety standards including standards for the safe administration and management of oral chemotherapy. J Oncol Pract. 2013;9(2 suppl):5s-13s.
4. Kelly J. The role of closed system transfer devices in mitigating the risks posed to healthcare workers in the handling of hazardous drugs. Entropy Research. March 2011; 1-12. http://bit.ly/U4AhXO. Accessed July 2, 2014.
5. Clark C. Exposure risks with cytotoxic drugs. Hosp Pharm Eur. 2010;49:15-16.
6. Connor TH, DeBord DG, Pretty JR, et al. Evaluation of antineoplastic drug exposure of health care workers at three university-based US cancer centers. J Occup Environ Med. 2010;52(10):1019-1027.
7. Special PP&P buyers guide: closed system transfer devices. Pharm Purchasing Prod. 2009;6(5):29-31.
8. Goodin S, Griffith N, Chen B, et al. Safe handling of oral chemotherapeutic agents in clinical practice: recommendations from an international pharmacy panel. J Oncol Pract. 2011;7(1):7-12.
9. Cuellar S. Safe handling of oral anti-cancer therapy—don’t ask don’t touch. Illinois Council of Health-Systems Pharmacists Spring Meeting; March 9, 2012. http://bit.ly/1xi6QR4. Accessed July 2, 2014.
10. Pick A. Home care of the oncology patient: the pharmacist’s role in the patient management and safe handling of oral chemotherapy. Power-Pak C.E. May 1, 2012. http://bit.ly/Ve7fGr. Accessed July 2, 2014.
11. Fransman W, Vermeulen R, Kromhout H. Occupational dermal exposure to cyclophosphamide in Dutch hospitals: a pilot study. Ann Occup Hyg. 2004;48(3):237-244.
12. Carey TE. Safe management of oral chemo-therapy drugs. Pharm Purchasing Prod. 2014;11(3):40-42.
13. Davis J, McLauchlan R, Connor TH. Exposure to hazardous drugs in healthcare: an issue that will not go away. J Oncol Pharm Pract. 2011;17(1):9-13.14. McDiarmid MA, Oliver MS, Roth TS, et al. Chromosome 5 and 7 abnormalities in oncology personnel handling anticancer drugs. J Occup Environ Med. 2010;52(10):1028-1034.
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