• Cases & Commentaries
  • Published April 2003

The 2-Week Itch

The Case

A 40-year-old woman with bipolar disorder (on trazodone) came to her primary care physician with new urticaria. She received a handwritten prescription for Zyrtec and Atarax.

The handwriting on the prescription was not unduly messy, but the pharmacist dispensed Zyprexa instead of Zyrtec.

At the follow-up visit for her urticaria 2 weeks later, the physician asked if patient was taking her medications as directed because the symptoms hadn't improved. She was specifically asked about the Zyrtec, at which point patient stated that she was not taking Zyrtec, but was taking a different medication—Zyprexa. As was her habit, the patient had brought all of her pills to the visit, so when the provider asked to see them, the error was immediately recognized.

The patient took the medication for about 2 weeks, with no adverse sequelae. Antipsychotic treatment lowers the seizure threshold and could have increased the severity and/or frequency of epileptic episodes, but this was not observed in this patient.

The Commentary

In the case presented here, a pharmacist misread a physician's handwritten prescription for ZYRTEC (cetirizine) and erroneously dispensed ZYPREXA (olanzapine). Look-alike, sound-alike medication mix-ups, such as this one, account for approximately 15% of all reports submitted to the Medication Error Reporting (MER) Program (1) operated by the United States Pharmacopeia (USP) in cooperation with the Institute for Safe Medication Practices (ISMP). The MedWatch program operated by the Food and Drug Administration has reported an almost identical prevalence of drug-name confusions in its database.(2) Published alerts about mix-up potential between the antihistamine, Zyrtec, and the antipsychotic, Zyprexa, first appeared in 1996.(3) Since then, other reports of Zyrtec–Zyprexa mix-ups have been submitted by practitioners to various error reporting systems.

Many drugs have strikingly similar names in appearance and/or sound.(Table) Confusion of such names can occur under the best of circumstances. We are told that the prescription in this case was ''not unduly messy,'' but illegible handwriting is a widely recognized problem. Difficult-to-read patient records and prescriptions waste time and produce errors,(4-6) causing serious injury and even death.(7)

Misinterpretation of a prescription is not the only way that errors occur with look-alike products. Errors also have happened because of container mix-ups—for instance when alphabetic arrangement of drugs place easily confused containers in close proximity. In this case, both medications begin with ''ZY,'' so the labels could easily be confused if stored next to one another on a pharmacy shelf. Drugs with similar appearing names may also display in close proximity on alphabetical lists. Thus, substitution errors may occur when pharmacists are selecting the product from a list on an order form or computer screen.

To avert problems, hospitals and pharmacies should consider the possibility of name confusion when adding a new product to the formulary. In addition, the ISMP web site (http://www.ismp.org) should be searched regularly to determine if reports of actual errors with this and other name pairs have been received already through the USP-ISMP Medication Error Reporting Program. If the potential for confusion with other products is identified, the necessary steps must be taken proactively to avoid errors. Incorporating this information in pharmacy computer system inventory files can actively signal staff about potential problems. Notations added to drug containers or near where containers are stored are another way to alert staff to potential confusion. Pharmacists should not store containers of these products near one another or list them adjacent to each other.

Products with similar names are more likely to be confused if they share additional similarities. With prescriptions for Zyprexa and Zyrtec there are many. These include: similar dosage form (both available as a tablet); two strengths that are shared (5 mg and 10 mg); the same route of administration (both oral); similar dosing frequency (5 mg to 10 mg daily); and a common dispensing quantity (30 tablets for a one-month supply).

Confusion also is compounded by incomplete knowledge of drug names, especially newly available products. Often, this is due to ''confirmation bias'' which leads one to ''see'' information that confirms one's expectation rather than information that contradicts it. That is, people are bound to see a more familiar drug name rather than one they have never come across or have seen only rarely. Poor handwriting coupled with look-alike drug names contributes to the potential for confirmation bias, especially when new, unfamiliar drugs are prescribed.

Since mix-ups between Zyprexa and Zyrtec are potentially serious, nurses, medical staff (including psychiatrists and allergists), and pharmacists must be alert to the possibility of confusion when patients are prescribed either drug. Most look-alike and sound-alike drugs do not share the same indications. Therefore, including the purpose on prescriptions will reduce the likelihood of such name confusions. For instance, writing ''Zyrtec (antihistamine)'' will help pharmacists and nurses differentiate the medication order from a prescription for Zyprexa. (Since Zyprexa is an antipsychotic, prescribers may be reluctant to include the purpose on prescriptions, but such concerns usually will not apply.)

Computerized prescribing is another way to reduce the potential for errors by presenting a clearly communicated prescription. Designing alerts in the computer system that warn about the potential for error and expressing the drug name in a way that differentiates one from the other (eg, ZyPREXA vs. ZyRTEC) may be helpful. In the absence of computerized prescribing, when name pairs are known to be problematic, reduce the potential for confusion by printing prescriptions using both the brand and generic name—in this case, Zyrtec (cetirizine). Verbal or telephone orders should be communicated only when absolutely necessary. Encourage the receiver to write down and read back all orders, spelling the product name.

The Food and Drug Administration (FDA) and the manufacturers are aware of mix-ups between Zyprexa and Zyrtec. In the future, problems with look and sound-alike products may be lessened because both the FDA and most pharmaceutical manufacturers have embraced the idea of testing proposed trademarks using front-line health care practitioners. Graphics of the handwritten names are sent to practitioners who provide assessments using testing protocols. Pronunciation tests also are used to help detect potential problems with new names. The FDA has stated openly their intention to publish guidance for the pharmaceutical industry to encourage this type of testing.

In addition, for many of the nonproprietary name pairs listed in the Table, in 2001 the FDA required that drug application holders use ''tall man'' lettering, in which drugs with similar names are differentiated by capitalization of dissimilar letters (eg, ClomiPHENE, ClomiPRAMINE), on their labels. A table appears on the FDA's web site.(8) These actions have dramatically reduced the number of error reports submitted to the ISMP. The technique can also be applied in computer systems to reduce errors during drug selection. A few new name pairs have been added to the FDA list since it was published.

In the meantime, physicians can lessen the chance of drug name confusion by adhering to the prescribing practices above and also by educating patients about their medications. Warn them about the risk of mix-ups and teach them to insist that the pharmacist show them the appearance of the tablets when dispensed. Zyrtec is a white, rectangular tablet marked 550 (5 mg) or 551 (10 mg). Zyprexa is a white, round tablet marked in blue ink with the tablet number 4115 (5 mg) and 4117 (10 mg).

Take-Home Points

What physicians can do:

  • Maintain awareness of look-alike and sound-alike drug names published by the ISMP in their newsletters and on their web site (http://www.ismp.org).
  • Use brand and generic names when prescribing or dispensing drugs known to be problematic.
  • Limit verbal orders. Pharmacists and nurses should write down and read back drug names.
  • Patients should be aware of potential for mix-ups, especially with problem name pairs. Include purpose of medication on prescriptions. Tell patients to insist on pharmacy counseling and verify correct medication and directions with pharmacist.

What systems can do:

  • The FDA and the pharmaceutical industry can help immensely by designing only those drug names found to be free of confusion during real-world testing prior to product launch.
  • Consider the possibility of name confusion when adding a new product to the formulary.
  • Computerize prescribing.
  • Use ''tall man'' lettering to differentiate products.
  • Install and utilize computerized alerts to remind providers about potential problems during prescription processing.

Michael R. Cohen, RPh, MS, ScD (hon)
Institute for Safe Medication Practices

References

1. U.S. Pharmacopeia. Use Caution - Avoid Confusion. USP Quality Review. 2001;76.
[ go to related site ]

2. Thomas MR, Holquist C, Phillips J. Med error reports to FDA show a mixed bag. Drug Topics. 2001;145:23.

3. ISMP Medication Safety Alert! Institute for Safe Medication Practices. October 23, 1996.
[ go to related site ]

4. A study of physicians' handwriting as a time waster. JAMA. 1979;242:2429-2430.[ go to PubMed ]

5. Shaughnessy AF, D'Amico F. Long-term experience with a program to improve prescription-writing skills. Fam Med. 1994;26:168-171.[ go to PubMed ]

6. Brodell RT, Helms SE, KrishnaRao I, Bredle DL. Prescription errors. Legibility and drug name confusion. Arch Fam Med. 1997;6:296-298.[ go to PubMed ]

7. Prager LO. Jury blames doctor's bad penmanship for patient death. American Medical News. November 22/29, 1999.
[ go to related site ]

8. Medication Errors: name differentiation project. U.S. Food and Drug Administration. Center for Drug Evaluation and Research.
[ go to related site ]


Table


Table. Examples of Easily Confused Sound-alike or Look-alike Drugs (1,4)



Generic Drug Names*

Brand Names

acetohexamide/ acetazolamide

Adderall/Inderal

amiodarone/amrinone § **

Alupent/Atrovent §

bupropion/ buspirone

Ambien/Amen

chlorpromazine/ chlorpropamide

Asacol/Os-Cal

clomiphene/clomipramine

Cardizem/Cardiem

cyclosporine/ cycloserine

Celebrex/Celexa/Cerebyx

daunorubicin/doxorubicin

Dynacin/DynaCirc

dimenhydrinate/diphenhydramine

Flomax/Fosamax; Flomax/Volmax

dobutamine/dopamine §

Indinavir/Denavir

glipizide/glyburide §

Lamictal/Lomotil/Lamisil ***

hydralazine/hydroxyzine

Lanoxin/Lonox

methylprednisolone/methyltestosterone

Levbid/Lopid/Lithobid

nicardipine/nifedipine §

Levoxyl/Luvox

prednisone/prednisolone

Lovenox/Lotronex

sulfadiazine/sulfisoxazole

Nizoral/Nasarel/Neoral

tolazamide/tolbutamide

Remeron/Zemuron

vinblastine/vincristine §

Vioxx/Zyvox

 

Zyrtec/Zyprexa ***


§ drugs have similar action or indication (eg, glipizide and glyburide are both oral hypoglycemics prescribed to Type II diabetics.).

*In 2001, the US Food and Drug Administration notified drug application holders for many of these products to use ''tall man'' lettering on their labels. A table that shows these changes appears on the FDA's web site.(8) The technique can also be applied to computer systems to reduce errors during drug selection.

**The United States Pharmacopeia and United States Adopted Names (USAN) has approved changing the nonproprietary name and the current official monograph title of amrinone to inamrinone (eye-nam-ri-none). The name change from amrinone to inamrinone became effective on July 1, 2000.

*** GlaxoSmithKline has substantially changed the container labeling to reduce the potential for dispensing errors due to confusion between its antiepileptic drug, LAMICTAL (lamotrigine) and LAMISIL (terbinafine), a Novartis product. The new label, now in pharmacies, highlights the ''…ICTAL'' part of the name by italicizing it and placing it in a yellow background with red characters (LAMICTAL). In addition, a message has been placed on the front label panel stating: ''CAUTION: Verify Product Dispensed.'' The FDA has supported this revision of the Lamictal package label. Also, Eli Lilly has agreed to revise the label of Zyprexa and will also use ''tall man'' lettering to differentiate the letter characters that are unique from ''Zyrtec.''

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