Cases & Commentaries
Slow Down: Right Drug, Wrong Formulation
A 65-year-old man presented to his primary care clinic for follow-up after a recent hospitalization for exacerbation of heart failure. His past medical history was significant for heart failure with reduced ejection fraction and atrial fibrillation. The physician noted the patient, once again, showed several other signs of decompensated heart failure and sent him back to the hospital for intravenous (IV) diuretic therapy and control of his atrial fibrillation. The admitting internal medicine resident, in concert with the cardiology consult team, initiated IV diuresis and restarted the patient's home beta-blocker and antihypertensive medications. The patient reportedly had not taken his beta-blocker in the 36 hours prior to admission. As the evening progressed, the patient developed increasing oxygen requirements, decreasing blood pressure, and worsening mental status. That night, he developed atrioventricular block, experienced a pulseless electrical activity cardiac arrest, and died.
As part of the clinical review process, the case was discussed in a morbidity and mortality conference. The review revealed the patient's home medication was metoprolol succinate 300 mg. Instead, metoprolol tartrate 300 mg was ordered on hospital admission and administered as a single dose. In the institution's computerized provider order entry (CPOE) system, the first formulation of metoprolol to populate into the ordering field was "Metoprolol Tab," which the system defined as metoprolol tartrate. Metoprolol succinate populated as "Metoprolol *Do Not Crush* SA" with "SA" standing for "sustained action," not "short acting."
The ordering physician was clear in chart documentation that the intent was to start extended-release metoprolol. Thus, the ordering of metoprolol tartrate at that dose was a prescribing error believed to have contributed to the patient's death. The review also determined that insufficient attention to human factors in the electronic health record played a significant role in the error and highlighted an opportunity for future enhancement of the CPOE system to include human factors thinking in the design.
by Mary G. Amato, PharmD, MPH, and Gordon D. Schiff, MD
Computerized provider order entry (CPOE) systems that incorporate clinical decision support have been shown to reduce overall medication error rates.(1,2) However, CPOE can also enable some types of errors—as demonstrated by this case, in which an error in drug selection may have been facilitated by how the drug name was displayed on the ordering screen.(3,4) The unclear and incomplete listing of metoprolol formulations along with confusing abbreviations on the ordering screen likely contributed to the patient receiving a single, full day's dose of metoprolol as the immediate-release formulation (tartrate) rather than the intended extended-release formulation (succinate). This distinction is clinically significant because absorption characteristics differ between the two formulations with earlier and 2 to 4 times higher peak levels as well as more peak-to-trough level variation occurring with immediate-release metoprolol. (5) Typically, if an oral immediate-release product is used to replace the sustained-release product, the daily dose should be divided into 2 to 4 doses per day to account for these differences. An excess single dose of metoprolol can result in severe bradycardia, hypotension, atrioventricular block, heart failure, hypoxia, and cardiogenic shock.
A study of the Dutch central medication incidents registry showed that 1 in 6 medication incidents were associated with information technology systems. Of these, 41% of the errors reported from community pharmacies involved choosing the wrong medication; most cases were due to confusion of medication names and poorly designed screens.(6) Other recent studies have attempted to identify, classify, and highlight contributing factors for the most common types of CPOE-associated errors.(7,8) One study reviewed medication errors from the MEDMARX error reporting system.(7) The other reviewed the United States Food and Drug Administration-funded Computerized Prescriber Order Entry Medication Safety (CPOEMS) medication error reports from several inpatient and outpatient facilities with a variety of CPOE systems.(8) Ordering the wrong formulation for oral medications was one of the most common types of CPOE-related errors in both studies.(7,8) This type of error was often prompted by the confusion created by the numerous ways of listing types of sustained-release formulation (e.g., SR, ER, SA, XL, XR, CD, or IR). Other studies have summarized CPOE-related errors and made recommendations to address the risks facilitated by CPOE systems.(9,10)
Further analysis of the CPOEMS data showed widespread variation in how drug names are displayed among various inpatient and outpatient CPOE systems (both within and between systems), which can result in confusion and errors. In addition to variations in the inclusion and order of brand or generic names, there were often confusing modifiers such as symbols, abbreviations, and site-specific designations, as well as differences in fonts, capitalization, and truncation of some drug names.(11)
Look-alike and sound-alike (LASA) medication names have long been recognized as a source of error, and CPOE systems can facilitate errors if similar drug names are in adjacent areas on drug order selection lists without any differentiating factors or alerts.(12,13) The Institute for Safe Medication Practices (ISMP) maintains a list of reported LASA names to help health care systems identify medications that may require extra safeguards.(14) Metoprolol tartrate and metoprolol succinate are included on that list, and descriptions of errors between the two formulations and have been featured in several ISMP Medication Safety Alert! newsletters.(15)
The Office of the National Coordinator (ONC) for Health Information Technology (IT) has promoted efforts to adopt and use health IT to improve health care. It oversees a certification program for electronic health records (EHRs) for physicians and health care systems electing to participate in the Medicare and Medicaid EHR Incentive Program. Although EHR certification criteria include a requirement for EHR vendors to attest to using a user-centered design and to conduct usability tests, the design and testing is highly variable among vendors.(16) ONC has also developed Safety Assurance Factors for EHR Resilience (SAFER) Guides to help health care organizations conduct self-assessments to optimize the safe use of their EHRs.(17) The organization has also recommended the establishment of a national Health IT Safety Center for patient safety organizations, health IT users, vendors, and researchers to share resources, identify issues, and implement solutions to improve the safety of health IT, but such a center has not yet been formed.(18)
Despite current efforts and certification standards, measures to prevent errors due to CPOE system display of medications are needed. While there has been widespread recognition of the potential for errors due to confusing display of drug names in CPOE systems (particularly with LASA medications), there has not been a unified approach to address this type of error, and regulations for standardizations of naming of drug formulations are lacking.
Experts have called for EHR developers, health care organizations and users, and government regulators to share responsibility and work together to improve the safety of EHRs by addressing interoperability, usability, and security.(19) To prevent CPOE-related errors, including those caused by confusing screen displays, we (the CPOEMS investigators) and others recommend the following (9,19):
- Greater focus on user-centered design, human factors, and workflow issues by EHR developers and health care organizations;
- Standardization of data displays, including drug names, among CPOE systems;
- Standardization and enhanced clarity for abbreviations or differentiations of extended-release (SR, ER, SA, XL, XR, CD) compared to immediate-release (IR) products;
- Clinical decision support that prevents ordering wrong formulations based on indication, dosing, and frequency;
- Adding indication-specific notes to some drug name displays to help differentiate among LASA medications;
- Improvement in the identification and reporting of CPOE-related errors including those involving drug name display;
- Greater sharing of CPOE-related errors within and across systems to provide feedback to institutions and vendors so all can learn how to improve CPOE design and usability;
- Ensuring vendors permit sharing of screenshots to illustrate design issues and concerns.
Although CPOE systems have enhanced medication safety, improvements are needed to take full advantage of these systems. Such improvements may help prevent fatal medication errors like the one in this case.
- Poorly designed computerized provider order entry systems may facilitate medication errors, particularly for medications that have different formulations, such as metoprolol.
- Computerized provider order entry systems have a wide variation in how drug names are displayed, which can lead to errors.
- The federal Office of the National Coordinator for Health Information Technology has recognized the importance of user-centered design to improve electronic health record usability and prevent errors.
- Further standardization and guidelines for computerized provider order entry displays including drug name displays are needed.
- Electronic health record developers, government regulators, and health care organizations and users should work together to improve the safety of electronic health records and computerized provider order entry systems.
Mary G. Amato, PharmD, MPH Department of Pharmacy Practice, MCPHS University, Boston, MA Sponsored Staff Brigham and Women's Hospital Boston, MA
Gordon D. Schiff, MD Department of General Internal Medicine & Primary Care Brigham and Women's Hospital Harvard Medical School Center for Primary Care Boston, MA
1. Nuckols TK, Smith-Spangler C, Morton SC, et al. The effectiveness of computerized order entry at reducing preventable adverse drug events and medication errors in hospital settings: a systematic review and meta-analysis. Syst Rev. 2014;3:56. [go to PubMed]
2. Jones SS, Rudin RS, Perry T, Shekelle PG. Health information technology: an updated systematic review with a focus on meaningful use. Ann Intern Med. 2014;160:48-54. [go to PubMed]
3. Koppel R, Metlay JP, Cohen A, et al. Role of computerized physician order entry systems in facilitating medication errors. JAMA. 2005;293:1197-1203. [go to PubMed]
4. Ash JS, Sittig DF, Poon EG, Guappone K, Campbell E, Dykstra RH. The extent and importance of unintended consequences related to computerized provider order entry. J Am Med Inform Assoc. 2007;14:415-423. [go to PubMed]
5. TOPROL-XL(R). Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2016. [Available at]
6. Cheung K, van der Veen W, Bouvy ML, Wensing M, van den Bemt PMLA, de Smet PAGM. Classification of medication incidents associated with information technology. J Am Med Inform Assoc. 2014;21:e63-e70. [go to PubMed]
7. Schiff GD, Amato MG, Eguale T, et al. Computerised physician order entry-related medication errors: analysis of reported errors and vulnerability testing of current systems. BMJ Qual Saf. 2015;24:264-271. [go to PubMed]
8. Amato MG, Salazar A, Hickman TT, et al. Computerized prescriber order entry-related patient safety reports: analysis of 2522 medication errors. J Am Med Inform Assoc. 2017;24:316-322. [go to PubMed]
9. Computerized Prescriber Order Entry Medication Safety (CPOEMS): Uncovering and Learning From Issues and Errors. Brigham and Women's Hospital, Harvard Medical School, Partners HealthCare. Silver Spring, MD: US Food and Drug Administration; December 15, 2015. [Available at]
10. Schiff GD, Hickman TT, Volk LA, Bates DW, Wright A. Computerised prescribing for safer medication ordering: still a work in progress. BMJ Qual Saf. 2016;25:315-319. [go to PubMed]
11. Quist AJL, Hickman TT, Amato MG, et al. Analysis of variations in the display of drug names in computerized prescriber-order-entry systems. Am J Health Syst Pharm. 2017;74:499-509. [go to PubMed]
12. Hicks RW, Becker SC, Cousins DD, eds. MEDMARX data report. MEDMARX Data Report: A Report on the Relationship of Drug Names and Medication Errors in Response to the Institute of Medicine's Call to Action. Rockville, MD: Center for the Advancement of Patient Safety, US Pharmacopeia; 2008. [Available at]
13. Look-Alike, Sound-Alike Medication Names. WHO Collaborating Center for Patient Safety Solutions. May 2007;1:solution 1. [Available at]
14. ISMP's list of Confused Drug Names. Institute for Safe Medication Practices. February 2015. [Available at]
15. ISMP Medication Safety Alert! Community/Ambulatory Care Edition. Picking the wrong metoprolol. September 2008;7:1. [Available at]
16. Ratwani RM, Hettinger AZ, Kosydar A, Fairbanks RJ, Hodgkins ML. A framework for evaluating electronic health record vendor user-centered design and usability testing processes. J Am Med Inform Assoc. 2017;24:e35-e39. [go to PubMed]
17. SAFER Guides. Washington, DC: Office of the National Coordinator for Health Information Technology. [Available at]
18. Health IT Safety Center Roadmap. RTI International. Washington, DC: Office of the National Coordinator for Health Information Technology; July 2015. [Available at]
19. Sittig DF, Belmont E, Singh H. Improving the safety of health information technology requires shared responsibility: it is time we all step up. Healthc (Amst). 2018;6:7-12. [go to PubMed]