February 2016 Volume 15 Issue 2

Government and industry fail to protect the public when they suggest “carefully following instructions” is enough to prevent vaccine errors Take our survey! t’s difficult to say this, but we were truly disappointed in our colleagues at the ISMP is updating its list of Look-Alike Drug Centers for Disease Control and Prevention (CDC) and the US Food and Drug Names with Recommended Tall Man Letters IAdministration (FDA) after reading about a recent analysis that representatives (www.ismp.org/tools/tallmanletters.pdf ). We from these agencies conducted on errors associated with administering just one are asking for your input by taking a 15-minute component of the two-component vaccine, MENVEO (meningococcal groups A/C/Y, survey, a copy of which appears on pages 5- W-135 diphtheria conjugate vaccine). 1 We greatly respect the important work carried 6. Please submit your responses by April 15 out by the CDC and FDA. However, the recommendations in the article seemed to online at: www.ismp.org/sc?id=1670 . Our list take a giant step backwards to an earlier time when healthcare providers tried un - of drug name pairs with tall man letters was successfully to manage and improve patient safety simply by exhorting staff to be first compiled after a survey in 2008 to help careful and to follow the rules. In the report, the central message to those who ad - healthcare organizations employ a standard minister Menveo was that, “By carefully following instructions included with the set of tall man letters to differentiate look- vaccine, administration errors with Menveo and similarly packaged vaccines can alike drug names. Our last update was 5 years be prevented.” 1The article was clearly missing an understanding of why such errors ago. We are considering a few name pairs occur and robust system strategies that would actually prevent ongoing errors with that have been involved in errors to add to Menveo, or PENTACEL (diphtheria and tetanus toxoids, acellular pertussis, po - this list, and we truly value your opinion! liovirus, Haemophilus b conjugate), which was also mentioned in the article. Vaccines with diluents also present similar problems (e.g., diluent given instead of mixing with the vaccine first). ISMP Fellowships ISMP is now accepting applications until Menveo and Errors March 31 for two yearlong Fellowship po - Menveo is a two-component vaccine supplied by GlaxoSmithKline (previously No - sitions starting in July 2016. We will be vartis) in two vials, one containing MenA lyophilized (freeze-dried) powder and the holding a call with potential applicants on other containing MenCYW-135 liquid. The contents of the two vials must be mixed March 2 from 1:00 to 2:00 p.m. ET to discuss prior to intramuscular (IM) administration of the positions and answer questions.Please the resulting solution. However, sometimes send a message to [email protected] if the liquid component of the vaccine has been you would like to participate. For details administered alone, without the lyophilized about applying for the Fellowships, please component—an ongoing error that ISMP first visit: www.ismp.org/sc?id=55 . published in 2014. 2 The vaccine comes in a car - ton containing five doses (10 vials total). A warning, “NEITHER MenCYW-135 NOR MenA COMPONEN T T O BE USED ALONE,” is only Paregoric, not “ tincture.” Pare - visible on the back panel of the carton, despite goric (anhydrous 2 mg per 5 mL, plenty of “white” space elsewhere. The vial la - 47%) was first formulated in the bels also contain language noting their proper early 1700s. Even though it had never been Figure 1. Warning, “NOT TO BE USED ALONE,” use, but one’s vision is not immediately drawn approved by the US Food and Drug Admin - does not catch the eye because it is in the same to the warnings to combine these products, istration (FDA), it remained on the US mar - red font as the other label information. because it is presented in the same color font ket for decades. In 2010 and 2011, FDA as the vaccine names ( Figure 1 ). Even though the vials are slightly different sizes began taking action against companies and have different cap colors, similarity in label style and color, and the small font that manufactured, distributed, or mar - size increase the risk of mistaking either vial as the complete vaccine. Also, both keted certain unapproved prescription vials list the root Men —one Men CYW-135 and the other Men A—which could be products. Paregoric was among them, and continued on page 2 —Fail to protect > continued on page 2— SAFETY briefs > February 2016 Volume 15 Issue 2 Page 2

> Fail to protect —continued from page 1 mistaken to simply mean that either vial contains the Men ingitis vaccine by those cont’d from page 1 who do not know it is a two-component vaccine. for a time, it was unavailable in the US. Nevertheless, upon the request of both pa - Several errors reported to ISMP also suggest that practitioners may mistakenly tients and health professionals, at least one believe the “liquid” component of the vaccine is just a standard diluent. 2 As such, manufacturer, Hi-Tech Pharmacal, inter - some errors involved administration of only the MenA powder after it was recon - acted with FDA to bring it back on the mar - stituted with a “generic” diluent (e.g., normal saline) or diluent supplied with an - ket, even though it remains an unapproved other vaccine (e.g., varicella; measles, mumps, and rubella). Some reported errors product. also involved accidentally diluting the MenA powder with another liquid vaccine, believing the liquid vaccine was a standard diluent. In addition, some of the errors in which the liquid MenCYW-135 component was given alone were reported as administration of just a “diluent,” without recognition that the “liquid” component is part of the vaccine.

All of these errors are serious because they leave people exposed to a potentially deadly disease—meningococcal meningitis, meningococcemia, or a related meningo - coccal disease. Furthermore, if an error goes unrecognized, which is certainly possible with these types of errors, individuals who have not received a proper dose will not know they are unprotected.

Although errors can be made by anyone preparing and administering vaccines, it should be noted that, in the US, unlicensed medical assistants who may not have Figure 1. Paregoric is not opium tincture 2%. the training or knowledge to recognize and address these challenges are often ad - ministering vaccines. About 40% of inpatient and outpatient vaccine errors reported Unfortunately, when the product was rein - to the ISMP National Vaccine Errors Reporting Program (VERP) involve unlicensed troduced, for some unknown reason the medical assistants who may be unfamiliar with the vaccine. nomenclature “opium tincture, 2%” was used in addition to “paregoric.” This is a MMWR Article problem for several reasons. First, “pare - Although ISMP has been writing about this type of error since 2014, the CDC-FDA goric” is the official name; next, paregoric analysis of Menveo errors and subsequent publication in the February 19, 2016, is NOT “opium tincture, 2%” and should Morbidity and Mortality Weekly Report (MMWR )1 was prompted by a question never be confused as such. Here’s why: posed to the CDC by a practitioner who wanted to know if it was safe to administer paregoric has 0.4 mg of morphine per mL a properly prepared vaccine dose of Menveo immediately after an error had been (2 mg in 5 mL). A typical adult dose would made by administering just the powder component alone. This led the CDC to be 5-10 mL, 1 to 4 times a day. A child would search the national Vaccine Adverse Event Reporting System (VAERS) database receive 0.25 to 0.5 mL/kg for each dose. But for reports of Menveo errors from March 1, 2010, through September 22, 2015. The opium tincture is an entirely different prod - agency identified 390 reports where only one component of the vaccine was ad - uct. Also known as , opium tinc - ministered to a total of 407 patients. Most patients (66%) received only the Men - ture contains 10 mg/mL (1%) of anhydrous CYW-135 liquid component, although some (34%) received only the MenA morphine. A typical adult dose is 0.6 mL, 4 lyophilized component, reconstituted with sterile water, saline, a different liquid times daily; a child would receive just 0.005 vaccine (e.g., hepatitis B vaccine), or an unspecified diluent. The data also identified to 0.02 mL/kg for each dose. A 10 kg child disproportional reporting of errors associated with Menveo, two times more often might get 5 mL of paregoric (anhydrous when compared to other vaccines. morphine 2 mg), but using opium tincture in error would result in the administration To their credit, the authors note that some errors with Menveo were detected by of an equivalent of 50 mg of morphine. routine processes as part of quality assurance, and they refer readers to other strate - gies available from the CDC to prevent vaccine administration errors. 3 Yet, it is dis - Confusion between paregoric and opium appointing that these strategies address all vaccines together and do not speak to tincture has been a longstanding problem the particular problem of two-component vaccines. While there is clearly good in - because paregoric was previously known formation about vaccine safety in this CDC reference, 3 it is also frustrating that the as “camphorated tincture of opium,” strategies begin with a recommendation to basically adhere to the five rights of which is easily confused with opium tinc - continued on page 3 —Fail to protect > continued on page 3— SAFETY briefs >

© 2016 ISMP. Reproduction of the newsletter or its content for use outside your facility, including republication of articles/excerpts or posting on a public-access website, is prohibited without written permission from ISMP. February 2016 Volume 15 Issue 2 Page 3

> Fail to protect —continued from page 2 medication administration and to provide staff training and education. We expected cont’d from page 2 more from the CDC and FDA, who respectively, help shape public policy and regulate ture, as happened with the Hi-Tech label - the labeling and packaging of vaccine products. We hope the agencies intend to do ing error in Figure 1 on page 2. Fatalities more than what is stated in the article. have been associated with mix-ups be - tween these products ( www.ismp.org/sc Error-reduction Strategies ?id=1661 ).The official name of “camphor - Of course, staff education about two-component vaccines and working carefully are ated tincture of opium” was changed to fundamental error-prevention strategies. But there are other high-leverage strategies “paregoric” to reduce the risk of mix-ups. that practitioners can utilize to reduce the risk of errors with two-component vaccines. It’s unclear where “2%” on the Hi-Tech Moreover, ISMP believes vaccine manufacturers must be required by FDA to improve label came from, but that would be vaccine labeling and packaging to reduce the risk of errors with two-component 20 mg/mL, or twice the amount in actual vaccines. This is a longstanding system problem, and the interim measures taken to opium tincture and 50 times the amount in date are not keeping patients or the public safe. paregoric. We contacted Hi- Tech and FDA to request immediate action to relabel Recommendations for Manufacturers and FDA the product as paregoric 2 mg per 5 mL The labeling on two-component vaccine containers (including those with as - (0.4 mg/mL). Until then, if you have this sociated diluents) must clearly distinguish each container, yet connect the two product, add labels to the bottles so they products so their contents are administered together. This is no easy task, but are not confused with opium tincture. it is one that manufacturers should undertake. Suggestions for consideration include: patch not adhering. Several practitioners have reported issues with Label the vials as “Vial 1 of 2” and “Vial 2 of 2,” or use a similar scheme to dis - transdermal fenta NYL patches from Ac - tinguish, yet link, the 2 vials whose contents must be administered together. tavis stating that the patches do not main - tain contact with the patient’s skin resulting Package two-component vaccines in redesigned vials in inadequate pain relief. This problem has that accommodate larger labels to reduce label crowd - affected multiple patients. For example, a ing and increase the font size of important text. patient with cancer-related pain had been wearing fenta NYL patches at home, prior Provide clear directions for use and warnings to ad - to being admitted to the hospital. The pa - minister the contents of both vials together on the tient was complaining of inadequate pain front label of the carton, each vial, and on the vial relief with the 100 mcg per hour patch. The cap. nurse checked the patch and noticed a large bubble in the middle such that the Make any warnings stand out on the label by employ - area of the bubble was no longer touching ing text in colors that differ from the standard text on the patient’s skin. It had been 48 hours the label. since the patch had been applied. A new patch was placed on the patient, but after Conduct usability testing with vaccine users to test 24 hours, the new patch also had a bubble, labels, packages, and preparation processes for safety, and the patient’s pain was not adequately clarity, and effectiveness. Look for ways that the vial Figure 2. The dual- controlled. No lotions, creams, or other labels can be misunderstood and whether anticipated chambered vial allows the substances had been applied to the pa - changes might improve understanding. Design labels diluent (top chamber) and tient’s skin prior to the patch being applied. the drug (bottom chamber) to reduce the risk of either vial being mistaken as the to remain separate until The patient had recently started radiation complete vaccine alone. the product is ready to be (not at the site where the patch was ap - used. plied), so it was thought that this might be When product stability and storage allow, employ integrated packaging that affecting skin oils, causing the patches to forces or facilitates proper mixing of the two components prior to adminis - not adhere to his skin. The patient was tration. For example, package the vaccines in dual-chamber vials similar to switched to extended-release oral pain SOLU-MEDROL (methyl PREDNIS olone) ( Figure 2 ), or in syringes similar medications, and his pain was controlled. to a European vaccine product, VIATIM (hepatitis A, typhoid polysaccharide vaccine) ( Figure 3 on page 4). Having a single expiration date for both In the outpatient setting, a patient using products is an additional advantage. fenta NYL patches at home reported prob - continued on page 4 —Fail to protect > continued on page 4— SAFETY briefs > February 2016 Volume 15 Issue 2 Page 4

> Fail to protect —continued from page 3 Ensure there are unique NDC num - cont’d from page 3 bers and barcodes on each vaccine lems with poor analgesia and mild with - component. drawal symptoms (nausea, , in - creased anxiety, sweating). Over a Include 2D barcodes on all vaccine 2-month period, he reported 4 patches products (although not required by falling off. He also noted that a gel-like sub - FDA presently). The government stance remained on his skin after one of should incentivize access to barcode the patches fell off. scanning systems for vaccine admin - Figure 3. The dual-chambered prefilled syringe istration similar to what was done for of the vaccine Viatim, from Sanofi Pasteur We’ve asked Actavis and FDA to investi - MSD, is available in Europe. This packaging electronic health records. option may reduce the risk of administering just gate. An Actavis representative said the one component of two-component vaccines. company has not had any recalls of the Recommendations for Healthcare Practitioners transdermal fenta NYL product. We think Circle or highlight critical information on vaccine containers or use flag-type this problem and the resulting loss of pain labels without obscuring label information. Clearly label or distinguish each control is important enough to mention, al - component if the manufacturer’s label could mislead staff into believing either though further investigation is needed. is the vaccine itself. Please report any similar experiences to FDA MED WATCH (www.ismp.org/sc?id= Establish a process to keep two-component vaccines together if storage re - 1660 ) or ISMP ( www.ismp.org/MERP ). Be quirements do not differ. Dispense the products together in a bag with an aux - sure to include the patch lot number(s). iliary label to remind staff to use both vials. Oral devices with mL-only dosing Where technology is utilized, require barcode scanning of both components of marks. Progress continues with manufac - two-component vaccines prior to mixing and administration. Barcode scanning turers making syringes with metric-only of both components prior to vaccine administration could help catch an error dose scales available. NeoMed has had if only one vial is being inadvertently used. mL-only syringes available for some time. We also have heard from BD and Baxter Document the NDC number, lot number, and expiration date of each vial in the regarding their plans to provide mL-only vaccination record or log before administration to confirm appropriate selection oral syringes. Medi-Dose and Health Care or preparation of both components of two-component vaccines. (With electronic Logistics are already advertising metric- inpatient records, prompts should require documentation of both components only devices. Also, dosage cups that meas - of two-component vaccines.) Documenting actual administration of the vaccine ure in mL-only are becoming available, should always occur after it is administered. although the ones we have seen so far have scales that are embossed on clear Be sure staff understand the differences between two-component vaccines plastic, making them difficult to read with and vaccines packaged with specific diluents. a colorless background or with certain liq -

References uids. However, we expect improvements 1) Su JR, Miller ER, Duffy J, et al. Notes from the field: administration error involving a meningococ - soon. We encourage pharmacies to tran - cal conjugate vaccine—United States, March 1, 2010–September 22, 2015. MMWR. 2016;65:161–2. http://dx.doi.org/10.15585/mmwr.mm6506a4 sition to printing patient directions on pre - 2) ISMP. Administering just the diluent or one of two vaccine components leaves patients unpro - scriptions labels in metric units and tected. ISMP Medication Safety Alert! 2014;19(10):1-4. dispensing metric-only dosing devices 3) Vaccine administration. Chapter 6. In: Hamborsky J, Kroger A, Wolfe S, eds. Epidemiology and pre - vention of vaccine-preventable diseases. 13th ed. Washington DC: Public Health Foundation; 2015. with oral liquid medications. www.cdc.gov/vaccines/pubs/pinkbook/vac-admin.html

If you would like to subscribe to this newsletter, visit: www.ismp.org/sc?id=386

ISMP Medication Safety Alert! Community/Ambulatory Care (ISSN 1550-6290) © 2016 Institute for Safe Medication Practices (ISMP). Subscribers are granted permission to redistribute the newsletter or reproduce its contents within their practice site or facility only. Other reproduction, including posting on a public-access website, is prohibited without written permission from ISMP. This is a peer reviewed publication.

Report medication and vaccine errors to ISMP: Call 1-800-FAIL-SAF(E), or visit www.ismp.org/MERP or www.ismp.org/VERP . ISMP guarantees the confidentiality of information received and respects the reporters’ wishes regarding the level of detail included in publications.

Editors: Michael Gaunt, PharmD; Michael Cohen, RPh, MS, ScD (hon), DPS (hon); Judy Smetzer, BSN, RN, FISMP; Ann Shastay, MSN, RN, AOCN. ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044. Email: [email protected] ; Tel: 215-947-7797; Fax: 215-914-1492.

ismp.org consumermedsafety.org twitter.com/ISMP1 facebook.com/ismp1 medsafetyofficer.org February 2016 Volume 15 Issue 2 Page 5

ISMP survey on tall man lettering to reduce drug name confusion

In 2008, ISMP compiled a list of look-alike drug name pairs with suggested tall man letters to be used in healthcare organizations to differentiate these products on pharmacy-generated labels, documents, and computer screens. It’s been 5 years since we last updated the list in 2011, so today we are seeking your input regarding a few more drug name pairs we are considering for addition to the list. We are also interested in learning how useful you find tall man letters, and any additional name pairs you believe we should consider for the list. Please submit your survey responses by April 15 at: www.ismp.org/sc?id=1670 .

Key: DK = Don’t Know/Uncertain

Aware of Add to List? Proposed Tall Man Lettering1 Question and Confusion Yes No DK Strongly Disagree Neutral/ Agree Strongly Alternate with Name Disagree Don’t Agree Suggestions Drug Name Pairs Pair? Know for Tall Man Yes No Lettering 1 Please tell us whether you are aware of any confusion or mix-ups with the drug name pairs below, whether you believe the name pairs should be added to our list, and whether you agree or disagree with the tall man letters selected to help differentiate the drug names. 1 You can also provide alternative suggestions regarding how to use tall man letters with each name pair. meth IMAzole and met OLazone meth IMAzole and methazol AMIDE eri BULin and epi RUBicin di AZEpam and diltia ZEM PONATinib and PAZOPanib rif AMPin and rif AXIMin oxy MORphone (and HYDROmor - phone, oxy CODONE, and Oxy CONTIN, already on list) dexame THASONE and dexmede- TOMidine penicill AMINE and penicillin 2 LEVOleucovorin and leucovorin 2 oxy BUTYnin (and oxy CODONE, already on list with and Oxy CONTIN) clo BAZam (and clonaze PAM, already on list with clo NIDine, clo ZAPine, and LORazepam) levo FLOXacin (and lev ETIRAcetam, already on list with lev OCARN- itine) zol PIDEM (and ZOLMitriptan, already on list with SUMAtriptan) DEPO-Medrol and SOLU-Medrol 3 idaru CIZUmab and idaru BICIN4 SAXagliptin and SITagliptin 5

1 To determine which letters to capitalize, we attempted to apply the CD3 rule. This methodology suggests working from the left of the word first by capitalizing all the characters to the right once two or more dissimilar letters are encountered, and then working from the right of the word back, returning two or more letters common to both words to lowercase letters. When the rule cannot be applied, because there are no common letters on the right side of the word, the methodology suggests capitalizing the central part of the word only. 2 No tall man letters recommended for one of the drug names in the pair 3 Solu- MEDROL is already on the list with Solu- CORTEF; suggest changing to SOLU-Medrol 4 IDArubicin is already on the list with DOXOrubicin; suggest changing to idaru BICIN 5 sita GLIPtin is already on the list with SUMAtriptan; suggest changing to SITagliptin continued on page 6 —ISMP survey on tall man lettering > February 2016 Volume 15 Issue 2 Page 6

> ISMP survey on tall man lettering—continued from page 5 All Some None Not Partly Neutral Effective Very Comments Question and Items or Effective Effective or DK Effective Most

2 In your facility, please tell us if tall man letters are used in conjunction with the stated items, and if you answer All-Most or Some, whether you feel this strategy is effective in reducing the risk of drug selection and drug identification errors. Computer drug selection screens (prescriber) Computer drug selection screens (pharmacy) Standard order sets Computer-generated pharmacy labels Shelf or bin labels Automated dispensing cabinet screens Computer-generated or electronic med - ication administration records (eMARs) Smart pump drug libraries Policies/protocols Other:

3 Please review the name pairs listed in Question 1 and those found on our current list at: www.ismp.org/tools/tallmanletters.pdf , and then let us know if there are any additional name pairs that you feel should be included (please specify): ______

4 Do you believe the use of tall man letters by the pharmaceutical industry on product labels helps to reduce drug selection errors? Yes No Not sure

5 Please select the category that best describes your profession (check one): Registered Nurse Licensed Practical Nurse Advanced Practice Nurse Pharmacist Physician Other Prescriber Pharmacy Technician Other:______

Answer questions 6-10 only if you use tall man letters in your facility.

6 What sources are used in your organization to determine which drug name pairs may benefit from tall man letters? (select all that apply) FDA-approved list of name pairs with tall man letters Internal facility risk and error data ISMP list of name pairs with recommended tall man letters Other: ______Not sure

7 For how many drug name pairs are you using tall man lettering differentiation? (each look-alike drug name pair counts as one) 1-10 11-20 21-30 > 30

8 Do you believe tall man lettering has prevented you from transcribing, dispensing, or administering the wrong medication? No Not sure Yes If Yes, please describe: ______

9 How are the purpose and intended use of tall man letters for look-alike name pairs communicated to clinical staff? (select all that apply) Policy statement issued Poster/memo posted on units Inservice/education/orientation Staff meetings Unknown Other:______

10 Do you use tall man letters for look-alike drug names that do not comply with ISMP or FDA suggested configurations, as listed on our current list at: www.ismp.org/tools/tallmanletters.pdf ? No Don’t Know Yes If Yes, please list: ______