PHARMACOLOGY CONSULT 12 www.JAAPA.com Volume 30 • Number 5 • May 2017 M edication safety is an important concern within any healthcare system. The effort to reduce medication errors stemmed from the early 1980s when the People’s Medical Society developed guidelines to help consumers prevent medication errors in hospitals and community pharmacies. 1 In November 1999, the Institute of Medicine (IOM) published the landmark report To Err Is Human: Building a Safer Health System, identifying medication errors as the most commonly occurring error in healthcare. 2 The IOM estimates the cost of medical errors to be on the order of billions of dollars per year nationwide. In spite of all these alarming emphases, neither healthcare providers nor the public identified medical errors as one of the most important problems in healthcare. 3 Interestingly, most of these groups believed that the number of deaths from preventable medical errors is lower than the reported figures from the IOM. Medication errors continued to be reported despite medication-safety efforts from dif- ferent regulatory agencies, including the California Department of Public Health, Board of Pharmacy, Joint Commission, and the FDA. Moreover, the same types of errors repeatedly occur. In 2015, the nonprofit Institute for Safe Medication Practices (ISMP) reported three cases of severe harm and death related to errors involving the use of low-dose methotrexate (defined as 7.5 mg to 25 mg weekly). 4 Two patients died from drug-drug interactions that caused toxic levels of methotrexate, and one patient required an extended hospital stay due to misinterpretation of the directions of a “once weekly” dose as a “once daily” dose. 4 Fatal or harmful errors related to low-dose meth- otrexate have been reported on multiple occasions by ISMP since 1996. A systematic literature review in 2014 revealed that 47% of all serious medication errors were caused by only seven drug classes, and methotrexate topped this list in percentage of incidents. 5 Furthermore, of the 74 articles that met the review’s inclusion criteria, 73 contained information (found in the FDA Adverse Event Reporting System) about a serious adverse reaction caused by methotrexate-related medication error. Not surprisingly, methotrexate continues to be involved in documented serious medication errors as recently as May 2015. 4 Does low-dose methotrexate deserve more respect from clinicians? Brent Luu, PharmD, BCPS, BCACP; George W. Rodway, PhD, APRN At the University of California, Davis, School of Nursing in Sacramento, Calif., Brent Luu is an assistant clinical professor of nursing and George W. Rodway is an associate professor of clinical nursing. The authors have disclosed no potential conflicts of interest, financial or otherwise. Mary Lou Brubaker, PharmD, PA-C, department editor DOI:10.1097/01.JAA.0000515554.91731.82 Copyright © 2017 American Academy of Physician Assistants ABSTRACT Medical errors associated with low-dose methotrexate may be life-threatening. Prescribers should be cognizant of the medication’s toxicities and the persistent challenges in preventing adverse events. This article reviews the proper- ties of methotrexate and its common drug-drug interac- tions. Best practices from the Institute for Safe Medication Practices, aimed at reducing methotrexate errors, are highlighted. Keywords: methotrexate, low-dose, medication errors, toxic, prescribing, interactions WOLTERS KLUWER HEALTH AND PHARMA FIGURE 1. Chronic interstitial pneumonia caused by methotrexate toxicity. Copyright © 2017 American Academy of Physician Assistants