Medication Errors Involving L Insulins

Clinical Review Article Medication Errors Involving L Insulins Lucy A. Levandoski, PA-C Martha M. Funnell, MSN, RN, CDE In 1999, the Institute of Medicine reported that an estimated 44,000 to 98,000 people die each year from medical and surgical errors, making medical errors the eighth leading cause of death in the United States, above breast cancer and motor vehicle accidents. Of these deaths, more than 7000 were the result of medication errors. 1 According to the Adverse Drug Events Prevention Study Group, medication errors occur in all 4 major phases of the drug delivery process: ordering (49%), transcribing (11%), dispensing (14%), and drug administration (26%). 2 The United States Pharmacopeia, which has been instrumental in developing medication error reporting systems, developed MedMARx, an Internet-accessible system for the anonymous reporting of medication errors. In the MedMARx summary reports for 1999 and 2000, the 3 most frequently reported types of medication errors were: (1) failure to administer an ordered dose, (2) administering an improper dose, and (3) administering the wrong medication. 3 Medication errors are not unique to health care providers and pharmacists. It has been reported that 50% to 90% of all patients do not take their medication(s) correctly as prescribed, and nearly 20% of all prescriptions are never filled. 4 Insulin, anticoagulants, and opiates are classified as high-alert medications because significant morbidity and mortality occurs when these drugs are ordered and/or administered incorrectly. Errors with these high-alert medications accounted for 15% of the 33,806 medication errors reported in the MedMARx report. 3 In this report, insulin was involved in 9% of the errors that resulted in patient harm and in 4% of errors that were reported but that did not result in harm. 3 Whereas any medication error has the potential to cause some degree of patient harm, errors involving insulin can cause serious, potentially life-threatening complications, including severe hypoglycemia. This article focuses on medication errors that can occur when prescribing insulin, particularly the L insulins : Lantus (insulin glargine; Aventis Pharmaceuticals Inc., Bridgewater, NJ), lente (insulin zinc suspension) and lispro (insulin lispro, Humalog; Eli Lilly and Co., Indianapolis, IN). THE L INSULINS Medication errors involving insulin account for significant morbidity and mortality. Of special importance are the L insulins, a group of insulins that have lookalike and/or sound-alike names (eg, Lantus and lente) or are similar in appearance (eg, Lantus and insulin lispro). The pharmacologic characteristics of these insulins are described in Table 1. Lantus Lantus, a long-acting, once-daily insulin analog introduced in 2001, is typically prescribed as a component of an intensive insulin regimen to meet basal insulin requirements in patients with diabetes. Unlike other intermediate- and long-acting insulins, Lantus is a clear solution with a ph of 4. Its ability to provide basal insulinemia without a pronounced peak is due to its relatively low solubility at neutral ph. After subcutaneous injection, Lantus is neutralized, causing the formation of microprecipitates. Small amounts of insulin are then released slowly over the course of approximately 24 hours. 5 It is this unique absorption profile of Lantus that results in very predictable insulin levels over the 24-hour period with less risk for nocturnal hypoglycemia. 6 Because Lantus forms microprecipitates at neutral ph, it cannot be mixed with any other type of insulin preparation, all of which have a ph of 7. Mixing Lantus with another insulin will result in unpredictable pharmacokinetics of both insulins. Lente Lente insulin is an intermediate-acting insulin that has been available since the 1950s. It is a cloudy suspension containing zinc to retard absorption after subcutaneous injection. It can be used to provide basal insulin levels but is usually given twice daily (before breakfast and before dinner) because of its shorter Ms. Levandoski is clinical diabetes research coordinator, Washington University School of Medicine, St. Louis, MO. Ms. Funnell is director for administration, Diabetes Research and Training Center, University of Michigan, Ann Arbor, MI. www.turner-white.com Hospital Physician June 2005 19

Levandoski & Funnell : Medication Errors : pp. 19 22, 40 Table 1. Characteristics of the L Insulins Lente Insulin (human insulin Insulin Lispro zinc preparation) Lantus (insulin glargine) Onset of action < 15 min 3 4 h ~1 h Peak activity 0.5 1.5 h 4 12 h Flat Usual effective duration 2 4 h 12 18 h 24 h Appearance Clear Cloudy suspension Clear Route of administration SC SC SC Usual regimen Within 15 min before Individualized therapy; Once daily, at same or immediately after a meal typically in the morning and time each day commonly given twice daily Compatible mixed with: Ultralente, NPH Regular, semilente None Packaging 10-mL vial; 1.5-mL cartridge, 10-mL vial 10-mL vial of unique shape (taller and thinner 3-mL disposable delivery device than all other insulin vials) with a purple cap and a label that contains purple print NPH = neutral protamine Hagedorn; SC = subcutaneous. duration of action (12 18 h). The pre-dinner dose of lente insulin can cause nocturnal hypoglycemia because its peak activity occurs 4 to 12 hours after it is given; its greatest glucose lowering effect, therefore, will occur during the night. Unlike Lantus, lente insulin can be mixed with other insulins, usually regular insulin, but it is recommended that the mixture be injected immediately after being drawn up to prevent the excess zinc in the lente from binding with the regular insulin, which would blunt the effect of the regular insulin. It is ideal to give the two insulins as separate injections. Lispro Insulin lispro, often referred to as simply lispro, is a very rapid acting insulin analog that is prescribed to meet prandial insulin requirements. It can be given either alone, before each meal as a component of an intensive insulin regimen, or in combination with an intermediate-acting insulin such as neutral protamine Hagedorn (NPH) or lente as part of a more conventional twice-daily insulin regimen. 7 MEDICATION ERRORS WITH LANTUS AND LENTE INSULIN There have been several reports of insulin-related medication errors involving confusion between Lantus and lente insulin. 8 10 Indeed, the similarity between Lantus and lente insulin prompted the Institute for Safe Medication Practices (ISMP) to issue a warning regarding the potential for errors with both written and verbal orders for these insulins. 11 Misinterpretation of a handwritten order is more likely to occur (and less likely to be detected) with medications that have similar spellings and similar indications. The similarities between Lantus and lente are an excellent example of this problem. The words Lantus and lente can look very similar when written carelessly. The error is unlikely to be detected by the pharmacist, especially if the instructions are vague, such as take as directed. The potential for harm occurs if the patient was instructed by his or her health care provider to take a specific dose of Lantus at bedtime but instead takes an equivalent amount of lente insulin, which has an entirely different pharmacokinetic profile and is likely to produce significant nocturnal hypoglycemia, especially if the entire dose is given as a single injection at bedtime. Lack of familiarity with any new drug can result in medication errors. One of the first reports of a medication error involving Lantus occurred shortly after it was released on the market. A diabetes educator suggested the use of Lantus insulin in a patient with difficult-tocontrol diabetes. The patient s primary physician was unfamiliar with Lantus and ordered lente instead. Fortunately, this error did not result in patient harm. 10 MEDICATION ERRORS WITH LANTUS AND LISPRO Errors involving confusion between Lantus and insulin lispro have also been reported. 12 Most health care providers and persons with diabetes have been taught that fast-acting insulins are clear solutions and longacting insulins are cloudy suspensions. Accidental administration of lispro instead of Lantus is quite possible because, even though they are packaged in differentshaped bottles, both insulins are clear. 20 Hospital Physician June 2005 www.turner-white.com

The consequences of confusing Lantus with any one of the fast-acting, clear insulins such as lispro can be significant. Patients who mistakenly inject lispro at bedtime instead of Lantus are at risk for severe nocturnal hypoglycemia. Conversely, patients who mistakenly give Lantus preprandially, instead of lispro, are likely to experience significant postprandial hyperglycemia because of the pharmacokinetic and pharmacodynamic differences of these insulin preparations. A recent report in Diabetes Care 12 described two instances in which patients inadvertently took insulin lispro at bedtime instead of Lantus. Both patients had a history of taking their insulin correctly for 2 to 3 months prior to the medication error, and no cognitive or visual disorders were present in either patient at the time of the mistake. One patient s blood glucose dropped from 160 to 57 mg/dl within 2 hours of mistakenly injecting 22 units of lispro. The patient was referred to the emergency department for reversal of hypoglycemia with intravenous dextrose after nausea prevented further treatment with oral carbohydrate. The patient recovered fully. The second patient inadvertently injected 17 units insulin lispro and experienced a precipitous drop in her blood glucose from 315 to 67 mg/dl over a 3-hour period despite almost continuous consumption of oral carbohydrates. The patient s blood glucose did finally stabilize at 85 mg/dl with no further intervention required. In both of these cases, well-educated patients made a potentially serious error with insulin administration due to the similar appearance of Lantus and insulin lispro. SUGGESTIONS FOR REDUCING MEDICATION ERRORS WITH INSULIN Because medication errors involving insulin can be life threatening, every effort should be made to reduce the possibility for error. All members of the health care team need to work diligently to ensure that insulin errors are minimized or eliminated. It is imperative that those who prescribe insulin be familiar with the various insulin preparations, including the pharmacokinetic and pharmacodynamic properties of each. In addition, all patients who take insulin should understand how insulin works, including peak action profiles. Patients on multiple-component insulin regimens must be instructed regarding how each individual insulin component affects blood glucose levels. Pharmaceutical companies should assist in educating health care providers about new insulin products, including providing information about potential and actual medication errors with these products. Measures for reducing medication errors associated Table 2. Recommendations for Reducing Medication Errors Associated with Handwritten Insulin Orders Avoid the use of single-letter abbreviations for insulin preparations Do not use L to specify lente insulin Do not use L to specify Lantus insulin Do not use U to specify units or ultralente insulin Never use u or U to indicate units; always write out the word units Never use trailing zeroes after decimals Use of 5.0 units may be mistakenly interpreted as 50 units Always use leading zeroes before decimals Use of.5 units may be mistakenly interpreted as 15 units Use preprinted prescription pads or computer technology Have staff assistant write prescription neatly then obtain prescriber s signature Use print rather than cursive Limit each prescription to only 1 medication Provide clear and complete directions Do not write as directed Ensure the prescription has the prescriber s contact information Read over all medication orders for clarity and potential areas of confusion Data from Brodell et al, 13 Grissinger and Peterson-Falcone, 14 Hester, 15 Teichman and Caffee. 16 with written insulin orders are provided in Table 2. Medication errors due to illegible handwriting or use of abbreviations or symbols are among the easiest to prevent. When ordering insulin, the entire name of the insulin should be written. A single letter abbreviation, such as N for NPH or L for Lantus or lente, should not be used. 10,14 The American Diabetes Association, 17 the US Food and Drug Administration, 18 and the ISMP 19 strongly discourage using the letter U or u to denote units because of frequent reports of 10-fold insulin overdoses because the U was misinterpreted as a 0 (zero). Patient-Specific Measures Diabetes, especially insulin-dependent or insulinrequiring, is one of only a few chronic illnesses that require daily if not more frequent patient involvement in treatment decisions. Self-management skills, including self-monitoring of blood glucose, dose adjustments, meal planning, and insulin injections, are essential components of diabetes care. Patient education is critical to preventing medication errors with insulin. An educated patient is less likely to make insulin administration errors but is not exempt from making them. All patients who take insulin should be instructed www.turner-white.com Hospital Physician June 2005 21

Table 3. Recommendations for Reducing Patient-Related Insulin Administration Errors Make certain that patients know the pharmacologic differences between their individual insulins Make sure patients are able to identify the insulin by its unique packaging Shape of vial (Lantus vial is taller and thinner) Color of label (eg, purple print on Lantus) Color of vial cap (eg, purple versus magenta) Provide tips to help prevent administration errors Store each insulin in a separate location (eg, keep Lantus on the counter and lispro on the table) Use an insulin pen for lispro and a syringe for Lantus (Lantus is not currently available in a pen) Have patients create their own naming system for each insulin used in their regimen: Fast insulin (lispro) versus slow insulin (Lantus, lente) Mealtime insulin (lispro) versus basal insulin (Lantus, lente) regarding the individual insulin components of their regimen and the correct usage of the insulin. Teaching tips that suggest ways to avoid confusion and ensure that the correct formulation is being used help avoid errors in taking insulin (Table 3). For example, in an intensive insulin regimen that uses Lantus insulin along with a fast-acting prandial insulin such as insulin lispro, the fast-acting prandial insulin can be given via an insulin pen to reduce the possibility of accidentally giving Lantus insulin before meals. This strategy would also reduce the likelihood of inadvertently giving a fastacting insulin instead of Lantus. The use of insulin pens also eliminates the possibility of mixing Lantus with the fast-acting insulin. 20 CONCLUSION Prescribing medications for patients is an integral part of health care delivery. As such, it must be given the same degree of importance as any other component of health care delivery. Extreme care must be exercised when prescribing insulin because of the potential for life-threatening complications associated with administration of the wrong insulin preparation or the wrong insulin dose. Every effort should be made to write insulin prescriptions carefully with the directions for use clearly delineated. Pharmacists should not hesitate to question either the patient or the prescribing health care provider about a new insulin prescription, especially if it is inconsistent with previously prescribed insulin preparations. Whenever a health care provider makes a change in a patient s diabetes regimen, either in the insulin type, the insulin dose, or both, it is imperative that the health care provider take the time to make sure that the patient understands why the changes are being made and how the change will affect his or her diabetes regimen. Never rely on a patient s ability to remember even simple regimen changes. Always provide written instructions detailing the regimen changes. This step will save valuable office time and will likely reduce subsequent phone calls from patients or family members. In patients with insulin-treated diabetes mellitus, spending a little extra time explaining their insulin regimen can greatly reduce the likelihood of administration errors, especially with the L insulins. HP REFERENCES 1. Kohn LT, Corrigan JM, Donaldson MS, editors. To err is human: building a safer health system. Washington (DC): National Academy Press; 2000:1 287. 2. Bates DW, Cullen DJ, Laird N, et al. Incidence of adverse drug events and potential adverse drug events. Implications for prevention. JAMA 1995;274:29 34. 3. US Pharmacopeia. Summary of information submitted to MedMARx in the year 2000: charting a course for change. US Pharmacopeia; 2002. 4. Institute for Safe Medication Practices. White Paper. A call to action: eliminate handwritten prescriptions within 3 years. Huntingdon Valldy (PA): The Institute; 2000. 5. Insulin glargine (Lantus), a new long-acting insulin. The Medical Letter 2001;43 (W1110A):65 6. 6. Yki-Jarvinen H, Dressler A, Ziemen M. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group. Diabetes Care 2000;23:1130 6. 7. Campbell RK, Campbell LK, White JR. Insulin lispro: its role in the treatment of diabetes mellitus. Ann Pharmacother 1996;30:1263 71. 8. Berkowitz K. Lantus? Or Lente? Am J Nurs 2002;102:55. 9. Institute for Safe Medication Practices. Complexity of insulin therapy has risen sharply in the past decade part 1. ISMP Medication Safety Alert Acute Care Edition 2002 Apr 17;7(8):1 2. 10. Cohen MR. Confusion between Lantus and lente insulins. ISMP medication error report analysis. Hosp Pharm 2001; 36:936. (continued on page 40) 22 Hospital Physician June 2005 www.turner-white.com

11. Institute for Safe Medication Practices. Safety brief: FDA has approved Lantus (insulin glargine [rdna origin]). Concern is mounting that oral or written orders for lantus may mistaken as Lente. ISMP Medication Safety Alert Acute Care Edition 2000 May 3;5(9):1 2. 12. Adlersberg MA, Fernando S, Spollett GR, Inzucchi SE. Glargine and lispro: two cases of mistaken identity [letter]. Diabetes Care 2002;25:404 5. 13. Brodell RT, Helms SE, KrishnaRao I, Bredle DL. Prescription errors. Legibility and drug name confusion. Arch Fam Med 1997;6:296 8. 14. Grissinger M, Peterson-Falcone J. Medical error: prevention guidelines. Pharmacy Practice News 2001 Dec: 15 9. 15. Hester DO. Do you see what I see? Illegible handwriting can cause patient injuries. J Ky Med Assoc 2001;99:187. 16. Teichman P, Caffee AE. Prescription writing to maximize patient safety. Fam Pract Manag 2002;9:27 30. 17. Crowe DJ. The American Diabetes Association should be a leader in reducing medication errors [letter]. Diabetes Care 2001;24:1841. 18. Mahmud A, Phillips J, Holquist C. Stemming drug errors from abbreviations. Drug Topics 2002 July; 13:46. 19. Institute for Safe Medication Practices. Please don t sleep through this wake-up call. ISMP Medication Safety Alert Acute Care Edition 2001 May 2;6(9):1 3. 20. Schutta MH. Reducing mistakes in patient administration of glargine and lispro [letter]. Diabetes Care 2002;25:10 9. Copyright 2005 by Turner White Communications Inc., Wayne, PA. All rights reserved. 40 Hospital Physician June 2005 www.turner-white.com