Guidelines for the safe handling of IV-based hazardous drugs (HDs) are well established in the traditional pharmacy settings of hospitals and infusion clinics. However, the increasing availability of oral chemotherapy formulations means that a greater number and variety of locations are handling these medications than ever before. As 25% of new antineoplastic agents in development are oral formulations,1 it is imperative that health care professionals and caregivers both understand the risks associated with oral HDs and have the knowledge to handle them safely. This is a challenging goal, because guidelines are not as well established for oral agents as they are for parenteral agents. Additionally, there is a need to overcome the misconception that a medication made available for patients to take at home must therefore be safe to handle.
Expanding Risks of Hazardous Drugs
Antineoplastic agents are a specific category of HDs that pose a risk to health care workers—published evidence describing their harmful effects dates back nearly three decades. Although some of the effects of handling HDs may be relatively benign and short-lived (ie, dizziness, headache, minor hair loss, contact dermatitis, mucosal sores, and tissue injury), others are much more significant. These include damage to health care workers’ reproductive systems, which can result in miscarriages, infertility, and congenital malformations.2,3 The carcinogenic effects of HDs, such as an increased risk of leukemia in health care workers who have been exposed to these medications, also have been well reported.4
While the specific risks associated with exposure to oral antineoplastic agents have been less widely publicized, the potential for injury from direct contact with, or inhalation of, oral HDs is nevertheless apparent. Therefore, all oral HDs should be assessed for potential risk of exposure, as the risk is dependent, in part, on the formulation of the oral agent. For example, uncoated tablets pose a risk of exposure from dust via skin contact or inhalation, whereas coated tablets or other agents that remain intact and are administered to patients without crushing, splitting, or otherwise altering their formulations, pose less risk.
Oral hazardous drugs should also be assessed for their degree of carcinogenicity. Sources such as the International Agency for Research on Cancer (www.IARC.fr) can assist in identifying the carcinogenic potential of multiple agents.
Addressing the Spread of Oral HDs
Oral HDs pose unique practitioner- and patient-safety challenges because of their use in nontraditional settings. Due to the sophistication and precision required to produce parenteral medications, they are traditionally prepared in inpatient or other clinical settings. However, oral formulations are more ubiquitous, both in the inpatient and outpatient settings. Furthermore, distribution of oral HDs is no longer limited primarily to oncology-specific units, particularly when patients are admitted for conditions independent of the reason they are taking the oral antineoplastic agent. A patient may be taking an oral antineoplastic agent to address a previously determined cancer diagnosis, but if that patient is admitted to the hospital for an unrelated knee arthroplasty, that HD may be utilized in an unfamiliar setting.
In the outpatient setting, distribution of oral HDs can originate from a prescriber’s office, a specialty pharmacy, or even a local retail pharmacy, and this wide range of locations almost certainly results in a decrease in familiarity with hazardous oral agents. A further concern in the outpatient setting is the aforementioned misperception that oral HDs are safer to handle than parenteral HDs. These factors make it essential for all entities that handle and dispense oral HDs to provide extensive education about the risks of oral HDs, and seriously consider implementing systems to alert staff of potential risks associated with these medications. Consideration should be given to building automatic alerts into pharmacy information systems to help identify hazardous drugs. An alternative strategy would be to label certain medication bins as hazardous medication.
Oral HD Management
As we all are aware, published guidelines are not always directly applicable to real-world situations. When it comes to oral chemotherapy agents, there are gaps in the recommendations, especially those that apply to storage, handling, and patient education.5 For example, while guidelines indicate that tablets and capsules should be counted in a designated biological safety cabinet (BSC), by far, the majority of retail pharmacies (where these products are primarily dispensed) do not have a BSC. Furthermore, automated counting devices (which are often used in an outpatient setting) present another problem should they be used for oral HDs. These machines may place stress on the integrity of a capsule or tablet that could result in inadvertent cutting or crushing of the dose. This damage exposes the staff member who is using the equipment, as well as any staff members who subsequently use the equipment, not to mention any cross-contamination of other medication types used in the machine. For these reasons, automated counting machines should not be used for counting HDs. Instead, traditional counting trays and spatulas should be employed, and this equipment should be designated and labeled solely for use in handling oral HDs. After use, all equipment used should be cleaned in the same manner as other equipment used in the preparation of HDs.
Among the gaps in the existing guidelines for safe handling of oral chemotherapeutic agents is robust evidence on the effective use of personal protective equipment (PPE). However, both the Occupational Safety and Health Administration (OSHA) and the Oncology Nursing Society recommend the use of PPE in the preparation and administration of chemotherapy.1,6
During routine handling of non-injectable HDs and their associated equipment, workers should wear two pairs of ASTM-approved gloves7 (keep in mind that not all pharmacy gloves meet the ASTM international standard for chemotherapy handling). Thus, facilities that handle and dispense oral HDs need to maintain a proper inventory of chemo-specific gloves appropriate to the volume of prescriptions. Likewise, the facility should create a policy regarding the specific types and brands to be used within the organization. Proper PPE use always includes comprehensive hand hygiene, and after handling or preparing oral HDs, hands should be washed in the same manner as after the preparation of a hazardous parenteral product.
As a general rule, crushing oral HD tablets or opening capsules should be avoided, and liquid formulations should be used whenever possible. If the manufacturer of pre-made doses cannot meet your required prescription volume, consideration should be given to alternate-day dosing or rounding. If oral HD compounding is necessary (eg, crushing, dissolving, or preparing a solution or an ointment), these activities should be performed in a ventilated cabinet such as a BSC,7 and workers should wear impermeable gowns in addition to double gloves. The policy and procedure (P&P) manual should specifically address these matters.
Unfortunately, appropriate training and follow-up, especially for patients and family members, is limited. As such, this provides a unique opportunity for pharmacists to educate patients and families about risks associated with oral hazardous drugs. This should include describing why caution should be used when handling these agents, as well as providing the patient and/or family with specific supplies, such as gloves and disposal equipment.
Cleaning, Transport, and Disposal of HDs and Related Medical Waste
The disposal of unused or unusable, non-injectable dosage forms of HDs should be performed in the same manner as hazardous injectable dosage forms and waste.7 Thus, it is advisable for organizations to develop their own P&Ps based on currently available evidence and guidelines, and these P&Ps should be embedded within a general policy regarding the cleaning of equipment used for the preparation of oral HDs. At SwedishAmerican Hospital, oral hazardous medications are transported from pharmacy in plastic bags with a hazardous medication label affixed to the outside.
Although published guidelines remain somewhat ambiguous as to managing incidental waste (eg, medicine cups and product packaging) that has come into contact with oral chemotherapy agents in community settings, well-described guidelines and processes exist for the disposal of hazardous waste in traditional settings, and these can be adopted to the outpatient setting. All contaminated equipment should be cleaned initially using gauze saturated with sterile water. Then use a chemotherapy-rated detergent, followed by a sodium hypochlorite solution, and then a neutralizer before rinsing the equipment again. The gauze and rinse should be contained and disposed of as contaminated waste.7
Labeling and Dispensing
In addition to listing the same information required for all other medications, labeling for oral HDs should include an auxiliary label or an additional information section that clearly identifies the product as a hazardous medication to prevent improper handling. This labeling is particularly crucial now as identification of HDs is becoming more difficult and the locations where oral HDs are stocked, are becoming more widespread. Ambiguous instructions, such as use as directed, should be avoided if possible. Also, specific information, such as start and stop dates and total doses, should be included. All containers should be separated and individually labeled; boxes or bags of doses should never be taped together with a single label.
Hazardous drugs should be dispensed in the final dose and form whenever possible. However, most unit-of-use containers for oral liquids have not been tested for containment properties and caution must be exercised when using these devices.7 Most exhibit some spillage during preparation or use. Consideration also should be given to assisting patients and family members with any supplies, such as disposal equipment or gloves. This is a unique service a pharmacist can provide when dispensing or distributing hazardous medications.
Clinically, the use of oral antineoplastics offers many advantages for patients. For example, some oral antineoplastic agents provide the same efficacy as parenteral antineoplastic agents, with fewer side effects, and thus are more tolerable. Furthermore, oral agents are more convenient and can provide the patient with a sense that they are participating in their own treatment plan. However, these HDs are associated with numerous logistical and safety challenges, complicated by the fact that related guidelines are lacking in various ways. As a result, the responsibility for establishing P&Ps regarding the proper handling and management of oral HDs falls to the institutional and community settings in which they are dispensed and administered. This situation offers pharmacists a tremendous opportunity to play a significant role in the oversight of the proper use of these drugs in both inpatient and outpatient settings.
E. Thomas Carey, PharmD, received his doctorate in pharmacy from Creighton University in 1996. He has been the director of pharmacy services at SwedishAmerican Hospital in Rockford, Illinois, since 2000. Thomas’ professional interests include infectious disease, cardiology, medication error prevention, hazardous medication exposure prevention, and pharmacy management.
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