n 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.1According 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%), dispens-ing (14%), and drug administration (26%).2The United States Pharmacopeia, which has been instru-mental in developing medication error reporting tems, developed MedMARx, an Internet-accessible sys-tem 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) adminis-tering the wrong medication.3Medication 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.3In 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.3Whereas 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 Pharma-ceuticals Inc., Bridgewater, NJ), lente (insulin zinc sus-pension) and lispro (insulin lispro, Humalog; Eli Lilly and Co., Indianapolis, IN).
THE “L INSULINS”
Medication errors involving insulin account for sig-nificant morbidity and mortality. Of special importance are the “L insulins,” a group of insulins that have look-alike and/or sound-look-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 compo-nent of an intensive insulin regimen to meet basal in-sulin 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 subcuta-neous injection, Lantus is neutralized, causing the for-mation of microprecipitates. Small amounts of insulin are then released slowly over the course of approxi-mately 24 hours.5It 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.6Because Lantus forms microprecipi-tates 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 unpre-dictable pharmacokinetics of both insulins.
Lente
Lente insulin is an intermediate-acting insulin that has been available since the 1950s. It is a cloudy sus-pension containing zinc to retard absorption after sub-cutaneous 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
I
Ms. Levandoski is clinical diabetes research coordinator, Washington Uni-versity School of Medicine, St. Louis, MO. Ms. Funnell is director for admin-istration, Diabetes Research and Training Center, University of Michigan, Ann Arbor, MI.
Medication Errors Involving “L Insulins”
Lucy A. Levandoski, PA-C
Martha M. Funnell, MSN, RN, CDE
duration of action (12–18 h). The pre-dinner dose of lente insulin can cause nocturnal hypoglycemia be-cause 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 im-mediately 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 conven-tional 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 – 10Indeed, 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 med-ications that have similar spellings and similar indica-tions. The similarities between Lantus and lente are an excellent example of this problem. The words Lantus and lentecan 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 entire-ly different pharmacokinetic profile and is likeentire-ly to pro-duce 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 medica-tion 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-to-control diabetes. The patient’s primary physician was unfamiliar with Lantus and ordered lente instead. For-tunately, this error did not result in patient harm.10 MEDICATION ERRORS WITH LANTUS AND LISPRO
Errors involving confusion between Lantus and in-sulin lispro have also been reported.12Most health care providers and persons with diabetes have been taught that fast-acting insulins are clear solutions and long-acting insulins are cloudy suspensions. Accidental ad-ministration of lispro instead of Lantus is quite possible because, even though they are packaged in different-shaped bottles, both insulins are clear.
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.
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 noctur-nal hypoglycemia. Conversely, patients who mistakenly give Lantus preprandially, instead of lispro, are likely to experience significant postprandial hyperglycemia because of the pharmacokinetic and pharmacodynam-ic differences of these insulin preparations.
A recent report in Diabetes Care12 described two in-stances 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 cogni-tive 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 mis-takenly 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 inad-vertently injected 17 units insulin lispro and experi-enced 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 pa-tient’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 pharma-cokinetic and pharmacodynamic properties of each. In addition, all patients who take insulin should under-stand how insulin works, including peak action pro-files. Patients on multiple-component insulin regimens must be instructed regarding how each individual in-sulin component affects blood glucose levels. Pharma-ceutical companies should assist in educating health care providers about new insulin products, including providing information about potential and actual med-ication errors with these products.
Measures for reducing medication errors associated
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 abbrevia-tion, such as “N” for NPH or “L” for Lantus or lente, should not be used.10,14 The American Diabetes Asso-ciation,17the US Food and Drug Administration,18and the ISMP19strongly discourage using the letter “U” or “u” to denote “units” because of frequent reports of 10-fold insulin overdoses because the “U” was misinter-preted as a “0” (zero).
Patient-Specific Measures
Diabetes, especially dependent or insulin-requiring, is one of only a few chronic illnesses that require daily—if not more frequent—patient involve-ment in treatinvolve-ment decisions. Self-manageinvolve-ment skills, including self-monitoring of blood glucose, dose adjust-ments, meal planning, and insulin injections, are essen-tial components of diabetes care. Patient education is critical to preventing medication errors with insulin. An educated patient is less likely to make insulin admin-istration errors but is not exempt from making them.
All patients who take insulin should be instructed
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,13Grissinger and Peterson-Falcone,14Hester,15
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 fast-acting 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 compo-nent of health care delivery. Extreme care must be exercised when prescribing insulin because of the po-tential 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 hesi-tate 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 regi-men. Never rely on a patient’s ability to remember even simple regimen changes. Always provide written instruc-tions detailing the regimen changes. This step will save valuable office time and will likely reduce subsequent phone calls from patients or family members. In pa-tients 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
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(continued on page 40)
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)
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12. Adlersberg MA, Fernando S, Spollett GR, Inzucchi SE. Glargine and lispro: two cases of mistaken identity [let-ter]. Diabetes Care 2002;25:404–5.
13. Brodell RT, Helms SE, KrishnaRao I, Bredle DL. Prescription errors. Legibility and drug name confu-sion. Arch Fam Med 1997;6:296–8.
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