no hives about it: an evidence-based approach to managing

No Hives About It: An Evidence‐Based Approach to Managing Patients with

a History of Drug Allergies Bryan D. Hayes, PharmD, DABAT, FAACT

Clinical Pharmacy Specialist, EM & Toxicology

John Patka, PharmD, BCPS

Clinical Specialist, Emergency Medicine

Conflict of Interest

• Neither presenter has (nor does any immediate family member have) a vested interest in or affiliation with a corporate organization offering financial support or grant monies for this continuing education activity, or any affiliation with an organization whose philosophy could potentially bias the presentation.

Objectives• Design an antimicrobial plan to include cephalosporins, given a patient with a documented penicillin allergy

• Evaluate the risk of prescribing a sulfa‐based, non‐antimicrobial medication, given a patient with a listed sulfa antibiotic allergy

• Evaluate the risk of prescribing an opiate or opioid medication, given a patient with a reported history of opiate allergy

• Evaluate the risk of prescribing contrast media and alternative treatments, given a patient with a contrast media or iodine allergy

The Engagement is Off! Busting the Beta‐Lactam Ring and Other

Antimicrobial Cross‐Reactivity Myths

Bryan D. Hayes, PharmD, DABAT, FAACTClinical Pharmacy Specialist, EM & Toxicology

University of Maryland Medical CenterBaltimore, MD

53 y/o 53 y/o

Ciprofloxacin R

Levofloxacin R

TMP‐SMX I

Cefuroxime S

Cefazolin S

Ampicillin S

E. ColiE. Coli The patient is allergic to penicillin. What antibiotic should you recommend?

Nitrofurantoin

Cefpodoxime

Meropenem

Gentamicin

Ciprofloxacin R

Levofloxacin R

TMP‐SMX I

Cefuroxime S

Cefazolin S

Ampicillin S

2014 Midyear Clinical Meeting No Hives About It: An Evidence-Based Approach to Managing Patients with a History of Drug Allergies

© 2014 American Society of Health-System Pharmacists 1

71 y/o 71 y/o 68/46 mmHg68/46 mmHgT 38.9o CT 38.9o C

http://www.antimicrobe.org/printout/e26printout/e26manage/e26man13.jpg

The patient is allergic to penicillin. Vancomycin PLUS ???

Piperacillin/tazobactam

Ceftazidime/Cefepime

Aztreonam

Meropenem

<a href="https://www.flickr.com/photos/22095754@N03/2218417572/">ortizmj12</a> via <a href="http://compfight.com">Compfight</a> <a href="https://creativecommons.org/licenses/by‐nc‐nd/2.0/">cc</a>

PCN ‘Allergy’ HistoryPCN ‘Allergy’ History

Macy E, et al. J Allergy Clin Immunol 2014;133(3);790‐6.

Longer stayLonger stay

↑ C. difficile ABX↑ C. difficile ABX

↑ C. difficile, VRE, MRSA prevalence↑ C. difficile, VRE, MRSA prevalence

10%10%

β‐lactam ringβ‐lactam ring

Pichichero ME, et al. Ann Allergy Asthma Immunol 2014;112:404‐12.

Risk of AnaphylaxisRisk of Anaphylaxis

Penicillins: 0.015 – 0.004%Penicillins: 0.015 – 0.004%

<a href="https://www.flickr.com/photos/89066489@N07/8570840573/">The Clear Communication People</a> via <a href="http://compfight.com">Compfight</a> <a href="https://creativecommons.org/licenses/by‐nc‐nd/2.0/">cc</a>

Cephalosporins: 0.1 – 0.0001%Cephalosporins: 0.1 – 0.0001%

Idsoe O, et al. Bull World Health Organ 1968;38:159‐88.Kelkar PS, et al. N Engl J Med 2001;345:804‐9.



ContaminationContamination

Allergy DefinitionAllergy

Definition

Campagna JD, et al. J Emerg Med 2012;42(5):612‐20.

http://upload.wikimedia.org/wikipedia/commons/6/65/1886_Eli_Lilly_and_Company_newspaper_advertisement_image.jpg

Pichichero ME, et al. Ann Allergy Asthma Immunol 2014;112:404‐12.

Penicillin Cephalosporins to Avoid

Amoxicillin

Ampicillin

Cephalexin

Cefaclor

Cefadroxil

Cefprozil

Campagna JD, et al. J Emerg Med 2012;42(5):612‐20.

1st gen, (+) PCN anaphylaxis

1st gen, (+) PCN anaphylaxis

1st gen, (‐) anaphylaxis,

different side chain

1st gen, (‐) anaphylaxis,

different side chain

1st gen, similar side chain

1st gen, similar side chain

Campagna JD, et al. J Emerg Med 2012;42(5):612‐20.Pichichero ME. Diagn Microbiol Infect Dis 2007;57(3 suppl):13s‐18s.

+/‐

2nd gen, similar side chain

2nd gen, similar side chain

2nd gen, different side chain

2nd gen, different side chain

Campagna JD, et al. J Emerg Med 2012;42(5):612‐20.Atanaskovic‐Markovic M, et al. Pediatr Allergy Immunol 2005;16:341‐7.

3rd, 4th, 5th gen3rd, 4th, 5th gen

Romano A, et al. Clin Exp Allergy 2005;35:1234‐42.

Cephalosporin cross‐reactivityCephalosporin cross‐reactivity



53 y/o 53 y/o

Ciprofloxacin R

Levofloxacin R

TMP‐SMX I

Cefuroxime S

Cefazolin S

Ampicillin S

E. ColiE. Coli The patient is allergic to penicillin. What antibiotic should you recommend?

Nitrofurantoin

Cefpodoxime

Meropenem

Gentamicin

Ciprofloxacin R

Levofloxacin R

TMP‐SMX I

Cefuroxime S

Cefazolin S

Ampicillin S

The patient is allergic to penicillin. What antibiotic should you recommend?

Nitrofurantoin

Cefpodoxime

Meropenem

Gentamicin

Ciprofloxacin R

Levofloxacin R

TMP‐SMX I

Cefuroxime S

Cefazolin S

Ampicillin S

PCN in Cephalosporin‐allergic patient?

PCN in Cephalosporin‐allergic patient?

Romano A, et al. J Allergy Clin Immunol 2010;126(5):994‐9.Macy E. J Allergy Clin Immunol2011;127(6):1638‐9.

~ 5%~ 5%

Side chainSide chain

http://upload.wikimedia.org/wikipedia/commons/e/e8/Botswana_road_sign_‐_No_U_Turn.svg

CarbapenemsCarbapenems

Wall GC, et al. J Chemother 2014;26(3):150‐3.Kula B, et al. Clin Infect Dis 2014 Jul 21. [Epub ahead of print]Frumin J, et al. Ann Pharmacother 2009;43(2):304‐15.

J Allergy Clin Immunol2009;124:167‐9.

0.8%

Allergy 2008;63:237‐40. 0.9%

Ann Intern Med 2007;146(4):266‐9.

0.9%

N Engl J Med 2006;354:2835‐7.

0.9%

71 y/o 71 y/o 68/46 mmHg68/46 mmHgT 38.9o CT 38.9o C

http://www.antimicrobe.org/printout/e26printout/e26manage/e26man13.jpg






Aztreonam

Meropenem




Aztreonam

Meropenem

66 y/o 66 y/o 228/136 mmHg228/136 mmHgSpO2 84%SpO2 84%

http://upload.wikimedia.org/wikipedia/commons/5/5a/APO.jpg

Should furosemide be avoided in this patient based on history of sulfa allergy

to an unknown antibiotic?Yes

No

Am J Health‐Syst Pharm 2013;70:1483‐94.

Wulf NR, et al. Am J Health‐Syst Pharm 2013;70:1483‐94.



N Engl J Med 2003;349:1628‐35.

Retrospective cohort

Am J Ophthalmol2004;138:114‐8.

Retrospective case series

Pharmacother2006;26(4):551‐7.

Prospective observational

DataData

9 cases!9 cases!

Sulfonamide nonantibiotic in

sulfa‐allergic patient

Sulfonamide nonantibiotic in

sulfa‐allergic patient

Wulf NR, et al. Am J Health‐Syst Pharm 2013;70:1483‐94.Johnson KK, et al. Ann Pharmacother 2005;39:290‐301.

66 y/o 66 y/o 228/136 mmHg228/136 mmHgSpO2 84%SpO2 84%

http://upload.wikimedia.org/wikipedia/commons/5/5a/APO.jpg



No



No

Cephalosporins: Avoid similar side chains

Sulfonamide nonantibacterials ok in

patients with sulfonamide antibacterial allergies



I’m Allergic to Everything but Dilaudid™ and Allergic to Iodine but I’m Not an

Alien

John Patka, PharmD, BCPSClinical Specialist, Emergency Medicine

Grady Health SystemAtlanta, GA

Allergy History

• Often inaccurate

• Use of second‐line treatments

• Increased cost

• Confusion between allergy and adverse drug reaction (ADR)

Int Arch Allergy Immunol 2012;158:307–312Pharmacotherapy 2008;28(11):1348–1353

“I’m allergic to Bactrim™ because my aunt has an allergy to Bactrim™”

“My mom said I cannot take (that drug)” (37 year‐old man)

OPIATE ALLERGY

http://en.wikipedia.org/wiki/File:Afghanistan_16.jpghttp://www.geograph.org.uk/photo/3872606

Incidence of Opiate Allergy

• Allergy & anaphylaxis rare

• Common: urticaria, pruritus, sneezing, asthma exacerbation

• Natural & derivatives

• Morphine, codeine

• Semi‐synthetic

• Hydrocodone, oxycodone

• Synthetic opiates

• Fentanyl, meperidine, methadone(Opioid analgesics – cross allergenicity). In: DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village,Colorado, USA. Available at: http://www.micromedexsolutions.com/ (cited: 08/26/2014)

Opiate Adverse Reaction vs. Allergy

• Histamine release (ADR, non‐IgE)

• Hypotension, rash, pruritus, tachycardia

• Maculopapular rash

• IgE mediated (Allergy)

• Angioedema

• Urticaria

http://phil.cdc.gov/PHIL_Images/15382/15382.tif http://phil.cdc.gov/phil/details.asp, ID #14260

How to Treat Anaphylaxis

• Airway, Breathing, Circulation

• Epinephrine IM• Adult 0.3 to 0.5 mg (adult)

• Pediatric 0.01 mg/kg (0.3 mg max)

• Do not give antihistamine

• Do not delay

https://c1.staticflickr.com/3/2738/4499129802_a770e66f85_m.jpg



Intramuscular vs. SQ Epinephrine

34 ±14

8 ±2

0 10 20 30 40

Route IM

SQ

Simons: J Allergy Clin Immunol 2004;113:837

Time to Cmax (minutes)

Opiate Allergy and Cross‐Reactivity

• Rare

• Not well defined

• Case reports

• Inconsistent skin test results

• Antibody testing preferred

• C‐6 hydroxyl & N‐methyl group implicated

Clin Rev Allergy. 1991 Fall‐Winter;9(3‐4):309‐18(Opioid analgesics – cross allergenicity). In: DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village,Colorado, USA. Available at: http://www.micromedexsolutions.com/ (cited: 08/26/2014)

No hydroxyl

Structure Relationship

http://lifesciencesfoundation.org/events‐Morphine.htmlhttp://i.imgur.com/MhcGmUm.png

Opiate Cross Reaction Literature

• 2004 case series (N=30) with reported opioid allergy

• N=6 classified high probability of allergic reaction

• 4 patients prescribed opioids without adverse effects

• Reports with synthetic agents (fentanyl)

• Positive skin testing

• Lack of morphine cross‐reaction?

J Oncol Pharm Practice. 2004;10:177‐82J Emerg Trauma Shock. 2012 Jul;5(3):257‐61

Clin Rev Allergy. 1991 Fall‐Winter;9(3‐4):309‐18

How to Mitigate Opiate Allergy

• Select non‐opiate analgesic

• Choose agent from different opiate class

• Natural & derivatives

• Morphine, codeine

• Semi‐synthetic

• Hydrocodone, oxycodone

• Synthetic opiates

• Fentanyl, meperidine, methadone

(Opioid analgesics – cross allergenicity). In: DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village,Colorado, USA. Available at: http://www.micromedexsolutions.com/ (cited: 08/26/2014)

CONTRAST ALLERGY

http://en.wikipedia.org/wiki/File:Thorotrast.jpg



Radio contrast media (RCM)

• Monomeric

• Dimeric

• Ionic

• Nonionic

• High‐osmolality contrast (HOCM)

• Low‐osmolality contrast media (LOCM)

J Emerg Med. 2010 Nov;39(5):701‐7Curr Opin Allergy Clin Immunol 2011. 11:326–331

Mechanism of RCM Allergy

1. IgE mediated, immediate hypersensitivity

2. Membrane effect related to osmolarity

• Compliment

• Bradykinin formation

• Neither mechanism is well demonstrated

Mechanism of RCM Anaphylaxis

IgE mediated, immediate hypersensitivity

T‐cell mediated, delayed hypersensitivity

Not well demonstrated

RCM Anaphylactoid Reaction

• Membrane effect related to osmolarity

• Compliment

• Bradykinin formation

• Neither mechanism is well demonstrated

Office for Emergency Management. Office of War Information. Domestic Operations Branch. Bureau of Special Services. (03/09/1943 ‐ 09/15/1945)

Risk for RCM Allergy

• Risk Factors

• Older age

• Atopy, asthma

• Prior RCM exposure

• Female gender

• Use of nonionic or HOCM

• Cardiovascular disease

• Critically ill

Allergy 2013; 68: 1203–1206PLoS One. 2014 Jun 16;9(6):e100154. doi: 10.1371/journal.pone.0100154.

Testing for RCM Allergy

• Incidence of positive skin testing

• 90 Patients with suspected immediate‐hypersensitivity

• 8 (8.9%) confirmed with skin testing

• 51 patients with RCM associated anaphylaxis

• 33 (64.7%) confirmed with skin testing to at least one RCM

Allergy 2013; 68: 1203–1206PLoS One. 2014 Jun 16;9(6):e100154. doi: 10.1371/journal.pone.0100154.



Study Design RCM N Reaction, N (%)

Kim 2014 Case series LOCM 104 75%*

Bedolla‐Barajas 2013

Observationalcase series

LOCM 9918.2% mild6.1% moderate2% severe

Ho 2014 Case series LOCM 29,9620.11% mild0.037% moderate0.01% severe

Kopp 2008Post marketing

registryLOCM

74,717All, 1470 (2%)Severe, 14 (0.02%)

Prior reaction 1569 All (7.4%)+

Atopy 7696 All (4.1%)

Valls 2003 Case series 19,554All, 338 (1.7%)Severe, 13 (0.06%)

Low risk HOCM 13,670All, 304 (2.2%)Severe, 11(0.08%)

High Risk LOCM 5884All, 34 (0.6%)Severe, 3 (0.05%)

* anaphylaxis + hypotension+ p<0.0001 compared to all reactions

Premedication with RCM

• Treatments controversial

• Corticosteroids

• H1‐ & H2‐receptor antagonists

• Immunosuppressant (cyclosporine)

• Breakthrough reactions possible

Immunol Allergy Clin N Am 2014; 34:547–564Allergy 2005;60(2):150‐8

Reaction to RCM:Risk Factors & Premedication (N=19,402)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Risk Factor Without RiskFactor

Premedication WithoutPremedication

Severe

Moderate

Mild

Adapted from: Acta Radiol. 2008 Oct;49(8):902‐11

Contrast Media & Iodine AllergyLiterature Review

• Iodine allergy vs. intolerance

• “The risk of reaction in patients with a seafood allergy is similar (0.2‐17%) to other food allergies or asthma”

• “Without iodine in the body, a person cannot survive”

J Emerg Med. 2010 Nov;39(5):701‐7Curr Opin Allergy Clin Immunol 2011. 11:326–331

RCM & Shellfish AllergyInjections

(n)Contrast All

reactionsSevere

reactionsDeaths

All cases 112,003

HOCM

5546(5%)38

(0.003%)8

(0.007%)

Seafood Allergy

207 31 (15%) 1 (0.5%) 0

Other food allergy

307 41 (13%) 0 0

Asthma 340 38 (11%) 0 0

Priorcontrast reaction

1918 321 (17%)Not

reportedNot

reported

History of any allergy 2.2 x more likely to have a reaction no allergy history Primary allergy: seafood allergy

J Emerg Med. 2010 Nov;39(5):701‐7Ther Nucl Med 1975;124:145–52

World J Cardiol 2014;6(3):107‐11



Dispel the Myth!

• Identify “false” risk factors

• Shellfish/iodine allergy in patient (or other family member)

• Refrain from seeking iodine allergy during history

• Remove reference to seafood and iodine allergy from consent forms and questionnaires

American College of Asthma, Allergy, and Immunology Drug and Anaphylaxis Committee 2009

Patient CasesAudience Selection

Key Takeaways

• Perform a thorough allergy history before changing therapy

• If suspect true opiate allergy select non‐opiate, or different opiate class

• Seafood allergy does not increase risk of reaction to RCM

• Humans cannot be allergic to iodine

Bryan D. Hayes, PharmD, DABAT, FAACTE‐mail: [email protected]: @PharmERToxGuy

ALiEM.com

John Patka, PharmD, BCPSE‐mail: [email protected]



no hives about it: an evidence-based approach to managing

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