The Role of Drug Names and Packaging

in Medication Errors

Learning Objectives

• Describe potential errors caused by confusing look-alike or sound-alike (LASA) drug products

• Explain ways to decrease the potential for LASA medication errors

• Discuss the role of practitioners in decreasing LASA medication errors

Magnitude of the Problem

• The Institute for Safe Medication Practices (ISMP) has reported over 1,000 drug pairs of confusing drug names

• Confusion related to product names is one of the most common causes of errors reported to the U.S. Pharmacopeia (USP), Food and Drug Administration (FDA), and ISMP

Institute for Safe Medication Practices. http://www.ismp.org/Tools/confuseddrugnames.pdf.Starr CH. Drug Topics. May 15, 2000;144(10):49–58.

Examples of Errors Reported to ISMP

• Daptomycin and Dactinomycin– Generic names are similar, both are once

daily administration, both are lyophilized powders, both are yellowish in color

– Error detected prior to reaching patient attributable to differences in dosing

• Purinethol and Propylthiouracil– A child missed 6 months of chemotherapy

because propylthiouracil, an antithyroid drug, was dispensed instead of purinethol

Preventing Errors Involving Similar Drug Names

Name Changes• Levoxine and Lanoxin

– Similar brand names, both are tablet forms, both available as 0.125 mg tablets, both once daily administration

• Losec (omeprazole) and Lasix– Similar brand names, both dosed at 20 mg, names look

similar when written in cursive • After reports of errors arose, FDA and ISMP

advocated name changes– Levoxine changed to Levoxyl– Losec changed to Prilosec

Use of TALL-Man Letters• Use of mixed-case or enlarged letters to

emphasize the differing portions of two drug names:

zyPREXA zyRTEChydrOXYzine hydrALAZINE DOBUTamine DOPamine

• Use required by the FDA in 16 generic name pairs– For complete list, see Table 6-1 in textbook– For examples of name pairs on product labels, see

Figures 6-2 and 6-3 in textbook

Lists of Similar Name Pairs

• Limitations of some lists– Too long for practitioners to remember– Confirmation bias – Some name pairs may be on the list because

of packaging, not name– No way to distinguish between pairs with

frequent reports of confusion versus pairs with a single report

Lists of Similar Name Pairs

• Overcoming limitations– The Joint Commission and ISMP compiled

three smaller lists • Reviewed by an expert panel• Each pair includes recommendations to prevent

confusion within that specific pair– For potentially problematic name pairs encountered in

inpatient and outpatient care settings, see Tables 6-2, 6-3, and 6-4 in textbook

Lists of Similar Name Pairs

• Overcoming limitations– To comply with The Joint Commission 2009

standards for hospitals, organizations must:• Choose at least 10 pairs of LASA medications from

LASA tables listed on The Joint Commission Web site http://www.jointcommission.org

• Annually review the organization’s list of LASA medications and take actions

Generic Name Selection• The World Health Organization (WHO)

International Nonproprietary Names (INN) committee – Advocates for worldwide names

• The U.S. Adopted Names (USAN) Council assigns generic names in the United States– Multidisciplinary group

• WHO INN designates first, then USAN

Generic Name Mix-Ups• 9 of 10 pairs of potentially problematic names on

the The Joint Commission list include generic names

• The Joint Commission and ISMP encourage the use of both generic and brand name– Avoids confusion– Adds to redundancy

• Inclusion of “indication for use” can further decrease confusion– Most LASA products have different uses

Look-Alike and Sound-Alike Drug Choices

For additional LASA name pairs, see Tables 6-2 and 6-3 in textbook

Name Pairs Potential Consequences

Safety Strategies

CisplatinCarboplatin

Doses for carboplatin usually exceed maximum safe dose of cisplatin. Severe toxicity and death reported.

Install maximum-dose warnings in computer. Use stickers provided by cisplatin manufacturer. Do not store these drugs next to each other. Use generic names when prescribing.

HydromorphoneMorphine

Some prescribers have mistaken hydromorphone for the generic of morphine. Equianalgesic conversions result in significant overdose and even death.

Stock strengths that are dissimilar, e.g., stock hydromorphone 1 mg unit-dose cartridges and morphine 2 mg unit-dose cartridge. Ensure providers know these products are not interchangeable.

Trademark Suffixes• FDA requires each new formulation of a drug

to be distinguished by a suffix• Inconsistent use of suffixes may cause errors

– Example• Wellbutrin SR (sustained release) is given twice daily,

Dilatrate SR is once daily, Wellbutrin XL is once daily

• Misinterpretation of brand name suffixes may result in errors– Examples

• Percocet-5 to designate Percocet 5 mg, misinterpreted as Percocet 5 tablets

Ad Hoc Abbreviations

• Avoid the use of abbreviations• Interpretation of abbreviations

– Varies person-to-person– May be dependent on handwriting– Leads to confusion and errors

• Examples– “Norflox” for norfloxacin mistaken for Norflex– “HCT” for hydrocortisone mistaken for

hydrochlorothiazide– “Adria” for Adriamycin mistaken for Aredia

Nonprescription Brand-Name Line Extensions

• Federal regulations do not prevent nonprescription drugs from being marketed without FDA approval of product names

• Companies can capitalize on a well-known and trusted brand name– Product may not include any of the active ingredients of the

original branded product– Product may even be used for an opposing indication

• ISMP opposes brand name extension unless at least one ingredient from original product is present in the new product

Brand-Name Extensions

Original Kaopectate formulation:antidiarrheal

A newer Kaopectate formulation: contains docusate, thus it is a

stool softener

Same brand name foropposing indications

Foreign Drug Names and Impact of Reimportation

• No clearinghouse for worldwide brand names• Depending on the country:

– Same brand names may have different active ingredients in the United States versus foreign countries

– For examples of U.S. brand names with different active ingredients in Europe, see Table 6-5 in the textbook

– Suffixes are not standardized worldwide

Foreign Drug Names and Impact of Reimportation

• Increasing problem attributable to:– Internet pharmacies– Reimportation of less expensive medications

• Instruct patients traveling abroad to keep a list of medications by generic and brand name

U.S. Brand Names With Different Ingredients in Europe

For additional U.S. brand names with different active ingredients abroad, see Table 6-5 in textbook

Brand Name

Active Ingredient in United States

Active Ingredient in Europe

Dilacor Diltiazem– angina, hypertension

Digoxin– CHF, arrhythmia

Norpramin Desipramine– depression

Omeprazole– GERD, peptic ulcer

Ambyen (U.K.)Ambien (U.S.)

Zolpidem– insomnia

Amiodarone– arrythmias

Role of the FDA

• Premarketing review of proposed trademarks

• Postmarketing surveillance and risk management

Premarketing Review of Proposed Trademarks

FDA Office of Drug Safety, Division of Medication Errors and Technical Support (DMETS) reviews all trademarks

Premarketing Review of Proposed Trademarks

• DMETS has recommended disapproval of trademarks for the following reasons:– Names are too similar to existing names– Misleading, incorrect, or unsafe elements– Claims not supported by clinical data– Prefixes and suffixes may be confused with a common

medical abbreviation– Inclusion of dosage form or regimen in the proprietary

name– Similarities in storage environment– Unacceptable similarity between generic and brand

names

Postmarketing Surveillance and Risk Management

• Phase IV Medication Error Monitoring Program– Part of an NDA approval letter– Similar to a probationary period– Gives FDA and manufacturers time to

determine if a theoretical risk materializes into a true risk

Role of the Pharmaceutical Industry

• Trademarks must:– Be free of bad meanings or connotations– Be relatively easy to pronounce– Not add to medication errors– Not infringe upon other products– Undergo considerable scrutiny

• Linguistics algorithms• Cultural checks• Searches for similar names• Market studies with providers and consumers• Analyses of potential errors

Recommendations for Preventing Drug Name Mix-Ups

Role of Prescribers

• Maintain awareness of LASA drug names• Clearly specify dosage form, drug strength, and

complete directions on prescriptions• Use both brand and generic names when writing a

prescription• Include the purpose of the medication in the

prescription• Alert patients to the potential for mix-ups• Encourage patients to ask nurses or pharmacists about

unfamiliar medications they may be given• Avoid verbal orders; if used, require staff receiving

order to read back the order

Role of Practitioners and Organizations

• Determine purpose of medication prior to dispensing• Limit verbal orders; require read back of the transcribed

order (not “repeat back” of the spoken order)• Consider confusion potential when a medication is added

to the formulary• Computerize prescribing; if not, use pre-printed orders• List brand and generic names on medication

administration records and in automated dispensing cabinet (ADC) screens

• Use independent double checks

Role of Practitioners and Organizations

• Change appearance of LASA drugs on computer screens, ADCs, bins, carts, and labels by using TALL-man lettering, highlighting, color, or boldface

• Install and use computerized alerts• Configure computer screens to prevent LASA drugs

from appearing consecutively • Affix name alert stickers• Do not store LASA drug pairs together

– Separate drug products in pharmacy, nursing units, OR, etc.• Encourage reporting of errors and potentially

hazardous conditions (near misses)

Role of Drug Packaging and Labeling

Factors Affecting Packaging and Labeling Errors

• Human factors• Confirmation bias• Look-alike packaging• Readability• Color• Two-sided labels• Lack of contrast• Blister strips• Expression of:

– Concentration– Strength– Company name, logo– Product expiration dates

• Typeface• Excessive use of

warnings• Use of symbols• Nonstandard terminology• Unsafe abbreviations• Bar codes• Container design• Protective overwraps• External carton labels• Promotional materials• Drug shortages

Label-Specific Factors Contributing to Errors

• Information in an inconspicuous place

• Ambiguous presentation

• Information overshadowed by less important information

• Stylized graphics• Positioning of

corporate logos

• Print of suboptimal: – Size – Boldness – Contrast

• Labels read in less than ideal conditions:– Low light– Stressful situations

Human Factors

• Human and environmental factors play a major role in medication safety

• Simple modifications enhance readability:– Optimize lighting (significant reduction of errors at

146 footcandles versus 102 footcandles of light)– Using magnifying lenses– Printing information in exaggerated fonts– Regular eye exams– Rearranging work stations

Confirmation Bias• Definition: seeing or hearing what is familiar or

what a person wants to see or hear, rather than what is actually there

• Factors adding to confirmation bias– Similar packaging– Difficult to read labeling– Similar shape and size– Similar color– Stored in the same location

• For example of overcoming confirmation bias, see Figure 7-2 in the color photographs section of textbook

PARIS IN THE PARIS IN THE THE SPRINGTHE SPRING

Examples of Look-Alike Packaging• These ampuls are two different products

– External cartons are different– Internal amber packaging makes them difficult to

distinguish– Small writing and identical colored ampul neck rings add to

confusion

Look-Alike Packaging• CDC reported 100 patients in 21 states received tetanus

toxoid instead of purified protein derivative for tuberculin skin testing (PPD) during 2004

• Owing to look-alike packaging, tetanus toxoid was administered by the wrong route:– Administered intradermally versus intramuscularly

• Packaging was very colorful with stylized logos and writing– Practitioners distracted by color and style– Did not stop and read

• Manufacturer changed packaging to reduce confusion• For examples of look-alike packaging, see Figures 18-4

and 18-5 in textbook

Centers for Disease Control and Prevention. MMWR. 2004;53(29):662–4.

Readability of Labels and Packages

• Items may be correctly labeled, but if label is too cluttered it cannot be easily read (Figures 7-4 and 7-5)– Leads to confirmation bias– Bias compounded if containers stored in same location,

or stocked incorrectly– Common source of this type of error, IV stock solutions

(Figures 7-6 and 7-7)• Same volume sizes often stored together• Packaging is typically identical• Little variation in text color • Excessive writing on the bag because it serves as its own

“container”

ISMP Recommended Hierarchy of Information on Front Panel of

Prescription Drug Labels1. Brand name—bold,

sans serif type– Consider TALL-man

lettering

2. Generic name3. Dosage form4. Strength (metric units)5. Suggested route6. Warnings (if no space,

note where information can be found)

7. If injectable, note whether single-use, multi-dose, etc.

8. Manufacturer, distributor, packager information– Never place at top of

container because logos can be distracting and are not considered necessary for dispensing

9. “Rx only” statement and other federal requirements

Uses of Color

• Color coding: systematically applying color to aid in classification and identification– Relies on remembering what each color means– Example: ophthalmic preparations, color identifies drug

category • Color differentiation: color used to make

elements stand out or distinguish between items– Concern that practitioners may rely only on color and

not read labels– Example: pediatric formulation packaged in light blue,

adult version in orange

Uses of Color

• Color matching: colors have no special meaning, used to match one item to another– Example: a blue plug attaches to a blue

receptacle– Example: Broselow tape for pediatric

emergencies• For photograph of Broselow tape, see Figure 7-9

in textbook

Uses of Color• Color coding

Problems With Uses of Color

• Should not distract from drug name and strength• Use color coding with caution

– Slight color changes may be difficult to discern– Colorblind employees– American Society of Health-System Pharmacists

(ASHP), ISMP, and FDA oppose the use of color alone to identify drug products

• No single variable should be relied upon to prevent errors, including color

Problems With Uses of Color• Problem extends beyond medication packaging

– Syringe and needle packages also problematic– Overdoses have resulted

• For example of syringe packaging, see Figure 7-12 in textbook

• Possibly included in department specific procedures– Anesthesia– Labels indicate a drug category, not a specific drug

• For examples of color-code scheme, see Table 7-2 in textbook– User must add drug name and dose to avoid confusing

the end products

Need for Two-Sided Labeling

• Most common with IV fluids or piggyback medications

• Problem– Premixed IV bags look identical to one

another when stored face down– Foil overwraps have the same risk associated

with them– For examples of front and back package

labeling, see Figures 7-13 and 7-14 in textbook

Contrast• Examples of difficulty achieving contrast

– Printing on glass ampuls (Figure 7-15)– Labeling on aluminum foil–wrapped packaging

• Glare off packaging affects readability– Small package sizes do not allow room for contrast

(Figure 7-16)– Labeling on low-density polyethylene (LDPE) plastic

ampuls for respiratory therapy medications (Figure 13-3)

• Writing is embossed in transparent, raised lettering• Virtually impossible to read• Exempt from FDA bar coding rules• New IV formulations and eye drops are available in LDPE

containers, leading to wrong route errors as a result of packaging

Contrast• American Society for Testing and Materials

standards requires:– Contrast between drug names and amount of drug

per unit– Legibility testing requiring

• Prevention of errors with LDPE– Allow only pharmacy to order and stock respiratory

medications from wholesaler– Manufacturers should ship products in well-marked

boxes– Dispense ampuls in an outer package that can be

easily labeled– Do not store different respiratory medications in the

same bin

Expressions of Concentration and Strength

• Way in which strength is denoted may be confusing– Total volume displayed in small type size– Total volume and concentration not displayed near

each other– Expressions in concentration and ratios versus dose

can cause confusion• Example: epinephrine 1:1,000 versus 1:10,000

– Unit-dose packages labeled as amount per tablet versus amount per package

Expressions of Concentration and Strength

• Errors have involved entire volumes of a vial injected instead of the correct dose– Example: gentamicin 40 mg/mL supplied in a

20 mL vial– Correct dose is 40 mg (i.e., 1 mL)– Error: full 20 mL injected mistaking the need

for entire vial to be used for the dose– For photograph of package labeling, see

Figure 7-17 in textbook

Labeling of Blister Strips

• Nonprescription medications – Product name and strength may appear in a

random pattern across strip– Blisters may be cut and separated by patients

or for use in institutions• Leaves medication with no label

Company Name, Logo, and Corporate Dress

• Common logos or color schemes specific to a company may lead to confirmation bias

• Interference with readability– Intricate patterns or color schemes– Lines, bars, stripes– Company logos– For example of a manufacturer’s similar packaging

for different products, see Figure 7-23• Solution

– ISMP hierarchy recommends that manufacturer’s name always be placed at the bottom of the label

Symbols• Symbols may be misinterpreted by health

care providers and patients– Roman numeral IV as in CIV

• Meant to be a controlled substance class 4• Has been interpreted as intravenous

– Practitioners have crushed CIV tablets and injected them intravenously

– Slash through a circle depicting a pregnant woman

• Supposed to mean “Do not take this medication while pregnant”

• Interpreted by patients to be a birth control pill

Nonstandard Terminology

• “Single-use” versus “single-dose”– Nurses have misinterpreted “single-dose” to mean

administer all contents of container to a single patient• Lack of standardization of unit-of-measure

– Example: magnesium could be ordered as:• Percent (%), milligram (mg), gram (g), milliliter (mL),

milliequivalent (mEq) and milliosmole (mOsm)

• Nonstandard dose expression– Example: phenytoin equivalents (PE) for fosphenytoin

is a nonstandard dose expression associated with dosing errors

Label Reminders and Warnings• Label warnings may decrease error

potential – Warning statements may include:

• Danger, Warning, Caution, Notice, etc.

• Warnings may be highlighted by:– Use of bold type, boxes, or color– Example: undiluted potassium chloride

• Must have boxed warning for dilution on label• Black caps and “must be diluted” added to collar

around rubber stopper

Typeface• Sans serif is preferred typeface• Serifs are additional short lines stemming from

basic letter form• Sans serif means without serifs

– Plainer than serif fonts– Best for conveying short pieces of information– Letters with serifs take up more space

Example of Sans Serif Example of Serif Type

E, A, b, 3, 4 E, A, b, 3, 4 Arial Times New Roman

Expressing Product Expiration Dates

• Expiration date placement on products is regulated

• The way expiration dates are designated is not regulated– Examples of confusing expiration dating

• JN05—might be interpreted as January or June• 06 MAR 04—might be March 4, 2006 or March 6, 2004

• International Organization for Standardization (ISO) recommended format:– YYYY-MM-DD– Recommends against use of slash “/ ” in dates

because it may be mistaken for the number one “1”

Use of Unsafe Abbreviations and Dose Designations

• The Joint Commission National Patient Safety Goal prohibits use of “dangerous abbreviations” – For Do Not Use list, see Table 8-1 in textbook

• Dangerous abbreviations may be found in medication advertising or packaging– Abbreviations may increase confusion– QD “once daily” mistaken for QID “four times daily”

Bar Codes

• Bar code medication administration is a recognized way to decrease medication errors– FDA requires linear bar codes on all new

products coming to market

Additional Information on Bar Coding

Available in Slide Deck for Chapter 15

Container Design• Container design has led to administration

errors– Prefilled syringes for IV admixture preparation

(and needing further dilution) have been mistaken as immediate use products

• More than 40 deaths attributed to this error type • 1 or 2 g of lidocaine were administered directly into Y-

sites instead of being further diluted (Figure 7-30)– Containers requiring manual activation may result

in non-activated medication solutions• Patient may receive only diluent with no active drug

(Figure 7-31)

Container Design• Confirmation bias may be a factor in

container design– Products not intended for ophthalmic use when

packaged in bottles or tubes that look like eye drop containers

• Patients with poor eyesight have instilled “super glue” into their eyes

– Irrigation containers confused with IV solution containers

– Topical nitroglycerin packaged in tubes has been used sublingually

Protective Overwraps• IV medications with an overwrap should be

stored in the overwrap– Once an overwrap is removed, fluid may

evaporate from the bag• Evaporation leads to increased concentration

– Environmental factors may impact evaporation• Avoid writing directly on IV bags

– Volatile chemicals from the ink may leach through the bags and reach the solution

External Carton Labels• Labeling on external cartons is as important as labeling

on immediate containers• Avoid storing similar-looking containers near each other• Carefully inspect contents of larger containers

– Example: box lids of saline and potassium looked very similar and were confused resulting in death

Promotional Items and Advertisements

• Promotional materials may closely resemble actual products– Pens in the shape of ointment tubes

• For example of look-alike promotional item and medication package, see Figure 7-34 in textbook

– Bottles of antibacterial hand gel mistaken for risperidone oral liquid

– Placebo products used for demonstration may resemble the actual product with the exception of “demo only”

• For example of ambiguous demo labeling, see Figure 7-35 in textbook

Drug Shortages• Shortages disrupt the medication-use

process – Pharmacists must communicate shortages to

other practitioners– Communication about substitute products is

important– ASHP and University of Utah maintain a drug

shortage Web site• http://www.ashp.org/shortage• Provides information about shortages and how to

manage them

International Efforts• Foreign manufacturers may not necessarily

comply with U.S. safety recommendations– Example: Losec changed to Prilosec in the United

States to avoid LASA errors– The name Losec is still widely used outside the

United States• The same may be true for U.S. products used in

other countries• Countries must benefit from each other’s

lessons

Prospective Analysis to Prevent Labeling and Packaging Problems

• Decrease potential look-alike packaging and labeling through analyses conducted prior to marketing

• ISMP recommends that prototype testing include:– Failure mode and effects analysis (FMEA)

• Include all steps of medication-use process• Ordering, dispensing, administration, etc.

– Consider human factors engineering

References

Centers for Disease Control and Prevention. Inadvertent intradermal administration of tetanus toxoid–containing vaccines instead of tuberculosis skin tests. MMWR. 2004;53:662–4.

Institute for Safe Medication Practices. ISMP’s List of Confused Drug Names. Updated April 1, 2005. Available at: http://www.ismp.org/Tools/ confuseddrugnames.pdf

Starr CH. When drug names spell trouble. Drug Topics. May 15, 2000;144(10):49–58.