Q&A with Sylvia Bartel, RPh, MHP
Vice President, Pharmacy Services
Dana-Farber Cancer Institute

Pharmacy Purchasing & Products: What are the medication safety risks associated with chemotherapy agents? 
Sylvia Bartel: While the benefits of chemotherapy agents are well known, they are considered high-risk medications and just a slight variability in dosage can potentially lead to a tragic outcome. Even when administered appropriately, adverse reactions—such as low blood counts, fatigue, nausea, and vomiting—are expected. 

What makes chemotherapy especially risky, though, is the complexity associated with its administration. Chemotherapy is generally administered as part of a complex regimen, comprising multiple drugs in various doses and schedules. It is not unusual for the same drug to be used in multiple regimens at different dosages—opening up the opportunity for dosing confusion. In addition, chemotherapy regimens are ordered as a course; a chemotherapy course can consist of chemotherapy agents that are administered weekly, over several weeks, or daily over three, five, or seven days, for example. So, unless the order and schedule are written very clearly, daily doses can be confused with course doses. Also, the multiple routes of administration for these drugs contribute additional risks; for instance, methotrexate can be given as a continuous infusion, as an intramuscular injection, as a bolus, or intrathecally. Depending on the drug, an error made in the route of administration can be fatal.

Chemotherapy regimens are subject to multiple calculations, and this presents yet another opportunity for errors to occur; the greater the number of steps in any procedure, the greater the potential for error. In contrast to most other types of medication, chemotherapy doses are typically based on a patient’s body surface area. The formulas to calculate this measurement are in metric units, and as most US hospitals use scales that read weight in pounds, this means an additional calculation is required on top of the body surface area calculation. So, if an order is written in pounds, it needs to be converted to kilos before performing the body surface area calculation, which requires height and weight of the patient. There have been published reports of errors due to inputting a patient’s height instead of weight. One strategy to eliminate conversion errors is to use metric scales and have computer systems accept metric units only.

On top of these unique risks, chemotherapy is subject to the same risks as other medications, with errors arising from the use of verbal orders, illegible handwriting, transcription mistakes, misunderstood abbreviations, and labeling and packaging issues. 

PP&P: What strategies can be employed to prevent errors with chemotherapy orders?
Bartel: The ideal approach is to perform all ordering via an electronic order entry system, as this automation provides safeguards not available otherwise. Electronic order entry systems ensure complete order sets that include chemotherapy and support-care medications, as well as the correct route of administration and schedule. These systems can perform dosing calculations and allow providers easy access to pertinent laboratory values and patient demographics. 

Although an electronic order entry system is preferable, using a standard preprinted order form can help reduce the chance of ordering errors in the absence of automation. It is essential that preprinted order forms contain all of the necessary criteria for the correct dispensing and administration of that particular chemotherapy regimen (ie, chemotherapy drug name, dose per kg or m2, dosage, frequency, route of administration), as well as premedications, hydration, and any relevant post-administration orders. Also, the form needs to include patient demographic information, such as name, date of birth, medical record number, diagnosis, height, weight, body surface area, age, comorbidities, specific laboratory values/organ function readings, and allergies. Depending on how a patient initially responds to their chemotherapy regimen, dosages may have to be adjusted, so there should also be a designated area on the form to indicate dose reductions and the reason for these changes. There also should be an area to accommodate scheduling and sequencing of orders. Finally, administration criteria for lab parameters should be contained on the form as well. Ensuring all of this information can legibly fit on the document can sometimes pose a challenge. Therefore, it is important the order set form is an official, standardized document with contents organized in an easy-to-follow manner. 



In addition to implementing standardized ordering, facilities should establish dose ceilings or limits for each drug in an easy-to-access format. This forced function is part of the drug dictionary in our order entry system, and it does not allow an order to proceed when the maximum allowable dose has been exceeded. Establishing route restrictions is another critical ordering precaution; a provider would never be able to order vincristine intrathecally, for example, as our system limits administration of this medication to an IV push or infusion. Additionally, the dosing limit set for this drug is 2 mg. Thus, if a provider tried to order a 4-mg dose, it would trigger an alert stating that the dose limit has been exceeded. It also is important to track cumulative lifetime doses, either manually or electronically, if a patient is on a chemotherapy agent with a lifetime dose limit, such as doxorubicin.

Additional ordering guidelines, such as restrictions on the use of abbreviations, also can help prevent errors. To certain staff members, CTX might stand for cetuximab, while others might consider this an abbreviation for cyclophosphamide. It is a good idea to set guidelines for leading and trailing zeros. Trailing zeros can cause confusion; for example, 1.0 could easily be misread as ten. Having guidelines in place limiting which clinicians can order chemotherapy can help reduce errors as well. At our hospital, fellows in training cannot give chemotherapy orders without an attending physician’s co-signature. We also restrict midlevel practitioners from writing the first cycle of chemotherapy. 

An electronic order entry system can be a powerful tool for reducing safety risks associated with ordering chemotherapy, but caution still needs to be taken. For example, these systems will assist with conversions; nonetheless, it is important to ensure that the measurement system used for orders is consistent. So, when the order entry system converts weight in pounds to kilos, a forced function should ensure that weight can only be entered in one way. 

PP&P: How can technology assist with the scheduling of chemotherapy courses? 
Bartel: To schedule chemotherapy we use a tool called an infusion flow sheet, which is essentially an electronic infusion calendar that documents the patient’s entire chemotherapy course. This helps us keep track of where the patient is in their cycle, as well as when they start on their next cycle. This way when any provider, pharmacist, or nurse goes into the eMAR or order entry system, it alerts them to exactly where that patient is in their course. 

PP&P: What steps can pharmacy take to ensure the safe preparation of chemotherapy? 
Bartel: The preparation of chemotherapy must begin with the safe storage of these medications. Most pharmacies have a designated area to store chemotherapy because they are high-risk agents; however, it is equally important that these drugs are stored in a manner that reduces the risk of errors. Look-alike/sound-alike drugs (LASA) should never be stored together. For instance, cisplatin should not be next to carboplatin, nor should paclitaxel be next to docetaxel. Also, be careful when storing drugs with similar packaging. It is important to educate staff members charged with preparing these medications about potential issues that could result in errors, such as name similarities or different formulations. For example, doxorubicin also is available as a liposomal product, and staff needs to be aware of these formulation differences, as a product mix-up could potentially lead to using the wrong dosage. Including dose limit alerts for these products in the ordering system provides a further safety check. 

Standardize concentrations when possible and make sure that the manufacturer’s reconstitution guidelines are carefully followed to avoid preparation errors. It is advisable to organize standard concentrations and reconstitution guidelines into a spreadsheet for staff to access during preparation, as well as having this information in the pharmacy computer system.

Double checks are vital to the preparation and dispensing process. Whoever prepares the drug must document the amount used to reconstitute, the amount of drug withdrawn, and the amount added to the bag, and this data should be used by a pharmacist to check the finished preparation. In addition, the use of technology to assist with preparation should be considered. This includes the technician scanning the product bar code to verify the correct drug was chosen as well as taking a photograph of the amount of drug that will be added to the IV bag. If using a photograph is not an option, a pharmacist should check the amount of drug that will be added to the IV bag. After the technician has prepared the product, the pharmacist performs a final product verification before the product is dispensed to the nurse for administration. 

PP&P: What safety checks can be employed during administration of chemotherapy to prevent errors? 
Bartel: It is important to note that safety checks performed by all staff should be independent and sequential, as opposed to two staff members checking together, as this has the potential to cause confirmation bias. The nursing safety checks we employ include order verification, as well as patient and equipment verification. First, nursing double-checks the patient. Then, one nurse reviews the order that will be administered and double-checks the ordered drug, dose, and calculations. Once the drug product is received from the pharmacy, the nurse checks the pharmacy label against the original drug order. A second nurse performs this same check independently. The same practice should occur when setting up the smart pump: one nurse should set up the entire pump, including volume and infusion rate, and then a second nurse should recheck the settings and then begin the infusion. 

When using chemotherapy agents, it is especially critical to check the route of administration. There has been a great deal of concern and publicity surrounding chemotherapy agents given by the incorrect route, and these errors still occur even with education efforts and other safeguards in place. Having a unique process for verifying intrathecal products is particularly important. Giving vincristine via the intrathecal route, rather than intravenously, for example, is often a fatal error. Other drugs, such as daunorubicin or doxorubicin, also fall into this category. In our facility, these preparations are made in the pharmacy and rather than deliver them to the nurse or the medication room, the pharmacist delivers them directly to the provider who will administer the medication. The pharmacist and the provider then double-check the order and the drug. To help prevent administration route errors, our facility made the decision to ensure intrathecals look visibly different from other drugs; they are dispensed in a syringe with a pre-wet filter and an extension set on the end, and an alert label stating “administer intrathecally” is included on the syringe.

Finally, the last line of defense against administration errors is the patient. Patients should be educated about the drugs they are receiving—their dose, the route of administration, how often they should be receiving it, etc. We have actually had patients tell us that the color of a drug they are receiving does not look correct, and this caused us to pause and go back and recheck our steps. 

Before patients begin chemotherapy, an education session by the nurse and/or the pharmacist occurs and then during their infusion appointment, a nurse will review this information with them again. We like to have pharmacy involved when the patient comes in for subsequent infusions, as patients often still have questions about their medications. Patients appreciate the reinforcement these education sessions provide.

PP&P: What can pharmacy do to ensure successful implementation of technologies to assist with the chemotherapy-use process?
Bartel: A critical component to the success of these implementations is involving frontline users from the beginning of the project. Gaining their support can be challenging as staff are busy, so it is important to highlight safety benefits, as well as how these technologies will deliver efficiency. For example, to help gain provider buy-in for an order entry system, highlight how the new system will reduce medication query phone calls from the pharmacist or nurse and use institution-specific examples of errors that have occurred that will be averted by the use of the technology.

The other critical piece is making sure that practices are standardized prior to implementing automation. Order sets need to be agreed on and established and guidelines, such as dose ceilings, need to be put in place. Once information is standardized and policies and procedures are established, translating this information into an electronic system is much easier. If frontline staff is not part of the development process, they will find workarounds to the system. Make sure you appoint some superusers to support other frontline staff after the go-live period. It is critical that staff has support available to guide them and to answer questions as they are acclimating to a new system. After implementation, continue to get feedback on system performance and user issues so that further enhancements can be made.

Depending on how large your oncology service is, it might be helpful to gain some experience with the technology by performing pilots focused on a particular disease group or a provider as opposed to rolling out to the entire oncology department. If computerized provider order entry is being implemented as part of an organization-wide effort, do not test it in oncology first. Because of the complexity inherent with chemotherapy orders, it is wise to gain some experience using order entry on other units first and then apply those lessons learned to the oncology unit. 

PP&P: What do you wish these technologies could do that they currently are not capable of?
Bartel: Presently, when the physician selects the patient’s diagnosis in the order entry system, a list of possible regimens pops up. It would be more useful if the most appropriate regimen automatically came up based on the staging information in the patient’s electronic record. In addition, having the informed consent linked to the patient so that it is not in a separate area in the electronic medical record would be useful. The ability to program the system to make dose adjustments automatically, based on lab values, also would be useful. At the moment, while laboratory values are in the system, there is no capability for automatic dosage adjustments, so the provider must complete this step based on a review of the lab value. In the future we hope this can be automated. 

Sylvia Bartel, MPH, RPh, is vice president of pharmacy and clinical support services at Dana-Farber Cancer Institute in Boston, Massachusetts. She received her BS in pharmacy at the University of Wisconsin and an MS in public health from Northeastern University. Sylvia’s professional interests include oncology and therapeutic guideline development.

Unique Risks with Oral Chemotherapy

The use of oral chemotherapy agents is gaining momentum given the increased convenience, control, and tolerability these drugs can offer. Because medications delivered via capsule or tablet are considered less risky than those administered intravenously, these products may provide a false sense of security. However, oral chemotherapy has similar safety risks to its intravenous counterparts in terms of its adverse effect profile, narrow therapeutic window, and complex and varying dosing and schedules; in addition, it is subject to its own unique set of risks. 

With the new freedom oral drugs offer come new risks as a result of diminished professional and technological oversight. Providing patients complete autonomy over taking these medications means there are no checks in place to ensure the patient is taking the drug correctly—or at all. The risk of error increases when the orders are written outside of the order entry system and its attendant safety checks. The prescriptions for these oral agents are generally written by providers, and while they might use prescription writing software, it most likely is not capable of accommodating the complex calculations and scheduling associated with dosing these medications, and there may not be an oncology pharmacist or nurse involved in the order checking process. It is possible that the patient might take their prescription to a community pharmacy that does not have a lot of experience with these agents, and the pharmacist may not even know what the patient is taking the agent for. For example, cyclophosphamide is available orally and is used for multiple indications—not all of them are for treatment of cancer, and the same holds true for methotrexate, which can be used both for rheumatoid arthritis and breast cancer. Another cause for concern is how dose changes are recorded—if at all. So, if the patient has an adverse effect, calls their physician, and has the medication dosage reduced, there are no safety checks in place to ensure that this change is recorded on the patient’s record. Then, there is the issue of whether or not patients are safely handling these hazardous agents in the home environment. 

In order to better manage some of the risks associated with oral chemotherapy, we have put safeguards in place. We use prescription writing software that offers the same protections, such as calculations and dose limits, as our order entry system for intravenous chemotherapy. Also, we only allow one cycle at a time to be written so that the patient has to come back and see a provider to get a prescription for the next cycle. In addition to offering pharmacist counseling, we developed an oral chemotherapy education sheet that is reviewed with and given to these patients. Currently, we are in the process of developing measures to monitor patient adherence to oral chemotherapy.