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Just In Time: Pharmacist-

Focused Review of

Anaphylaxis Management

Jennifer Costello, PharmD, BCPS

Ambulatory Clinical Pharmacist

Internal Medicine Faculty Practice Saint Barnabas Medical Center

Livingston, New Jersey

Faculty Presenter:

Jennifer Costello, PharmD, BCPS

Ambulatory Clinical Pharmacist

Internal Medicine Faculty Practice

Saint Barnabas Medical Center

Livingston, New Jersey

Moderator:

Elena Beyzarov, PharmD

Director of Scientific Affairs

Pharmacy Times of Office of Continuing Professional Education

Plainsboro, New Jersey

This activity is supported by an educational grant from Mylan Specialty, LP.

Disclosures

Jennifer Costello, PharmD, BCPS, has no financial relationships

with commercial interests to disclose related to this activity.

Pharmacy Times Office of Continuing Professional

Planning Staff—Judy V. Lum, MPA, Elena Beyzarov, PharmD,

Jennifer Barrio, and Donna Fausak— have no financial

relationships with commercial interests to disclose related to this

activity.

The contents of this Webinar may include information regarding

the use of products that may be inconsistent with or outside the

approved labeling for these products in the United States.

Pharmacists should note that the use of these products outside

current approved labeling is considered experimental and are

advised to consult prescribing information for these products.

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Educational Disclaimer

Continuing professional education (CPE) activities

sponsored by Pharmacy Times Office of CPE are offered

solely for educational purposes and do not constitute any

form of professional advice or referral. Discussions

concerning drugs, dosages, and procedures may reflect the

clinical experience of the author(s) or they may be derived

from the professional literature or other sources and may

suggest uses that are investigational in nature and not

approved labeling or indications. Participants are

encouraged to refer to primary references or full prescribing

information resources.

Educational Objectives

Describe pathophysiology, presentation and risk

factors for anaphylaxis

Discuss the different treatment options available

for the treatment of anaphylaxis and detail when

they are appropriate

Counsel and educate patients on anaphylaxis

and how to use the different epinephrine auto-

injector kits

Pharmacy Accreditation

Pharmacy Times Office of

Continuing Professional Education

is accredited by the Accreditation

Council for Pharmacy Education

(ACPE) as a provider of continuing

pharmacy education. This activity is

approved for 1 contact hour (0.1

CEU) under the ACPE universal

activity number 0290-0000-12-079-

H01-P. This activity is available for

CE credit through July 3, 2014.

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Just In Time: Pharmacist-

Focused Review of

Anaphylaxis Management

Jennifer Costello, PharmD, BCPS

Ambulatory Clinical Pharmacist

Internal Medicine Faculty Practice Saint Barnabas Medical Center

Livingston, New Jersey

Historical Perspective

Actual discovery of anaphylaxis readily traceable to momentous sea voyage which included physiologists Charles Richet and Paul Portier, and oceanographer Albert Grimaldi (son of Prince of Monaco)

Portier and Richet coined the term anaphylaxis in 1901 when they described death of a dog from reinjection of toxin from a Physalia (Portuguese man-of-war)

Term derived from Greek words ana - (“up, back, again”) and phylaxis (“guarding, protection, immunity”)

Medicine in Stamps Charles Robert Richet (1850–1935): discoverer of anaphylaxis. Tan S Y, MD, JD and Yamanuha J* Professor of Medicine, John A Burns School of Medicine, University of Hawaii Singapore Med J 2010; 51(3) : 184

Epidemiology and Incidence Anaphylaxis: rare but life-threatening event

associated with approximately 1,500 deaths in U.S. annually

Estimated that 1 in every 3000 inpatients in U.S. hospitals suffers from anaphylactic reaction

Exact incidence of anaphylaxis difficult to estimate because not a reportable disease and there is debate regarding exact definition of anaphylaxis

Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States: an investigation into its epidemiology. Arch Intern Med. 2001;161:15–21.

Boston Collaborative Drug Surveillance Program. Drug-induced anaphylaxis. JAMA. 1973;224:613-615

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Epidemiology and Incidence

(cont.) Recent study found increase in incidence of

anaphylaxis From 46.9 cases per 100,000 persons in 1990 to 58.9

cases per 100,000 persons in 2007

Of identified causes: 33% caused by ingestion of specific food

18.5% from insect stings

13.7% for medications

Decker WW, Campbell RL, Manivannan V, et al. The etiology and incidence of anaphylaxis in Rochester, Minnesota: a report from the Rochester Epidemiology Project. J Allergy Clin Immunol. Dec 2008;122(6):1161-5

An Increasing Trend….

Incidence of anaphylaxis increasing worldwide

Specifically, food-induced anaphylaxis on the rise

Rise in anaphylaxis incidence appears most pronounced in children under age 5 years

Children under age 5 also the most at risk of hospitalization for food-induced anaphylaxis

Individuals with asthma at higher risk of anaphylaxis

Those with severe asthma identified to have highest risk of all

An update on epidemiology of anaphylaxis in children and adults. Koplin, Jennifer, Martin, Pamela, Allen, Katrina. Current Opinion in Allergy & Clinical Immunology: October 2011 - Volume 11 - Issue 5 - p 492–496

Pathophysiology Anaphylaxis caused by interaction of foreign antigen

with specific IgE antibodies found on mast cells and basophils

Anaphylactoid reaction caused by release of mast cell and basophils mediators triggered by non IgE mediated events; clinically indistinguishable from anaphylaxis

World Allergy Organization recommended replacing this terminology with: Immunologic anaphylaxis (IgE-mediated and non–IgE-

mediated)

Non-immunologic anaphylaxis (events resulting in direct, sudden mast cell and basophil release)

Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin

Immunol. May 2004;113(5):832-6.

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Pathophysiology and Triggers

Immunologic Mechanisms

IgE– mediated Food – peanuts, tree nuts, milk, egg, and shellfish

Venom from stinging insects – bees, hornets, wasps, and fire ants

Medications – penicillin and derivatives, biologic agents, NSAID

Latex from natural rubber – gloves, catheters, balloons, condoms

Radio contrast media and dyes

Airborne allergens – horse dander, plants

Non–IgE-mediated Immune complex/compliment mediated: many medications (eg,

biologic agents, radio contrast dyes, iron dextrans)

Pathophysiology and Triggers

Nonimmunologic (direct mast cell activation) Physical Factors

Cold, intense exercise, ultraviolet exposure

Ethanol

Opioids (eg, meperidine, codeine)

Nonimmunologic histamine release via direct mast cell degranulation

Radiocontrast media (RCM)

Cross linking and activation of mast cells

Angiotensin converting enzyme (ACE) inhibitors

Bradykinin production/accumulation

Idiopathic Anaphylaxis No specific trigger found

Mastocytosis/ clonal mast cell disorder

Signs and Symptoms of

Anaphylaxis

Symptoms generally seen within seconds to minutes after exposure

Skin

Occurs in up to 90% of presenting cases

Itching, hives (urticaria), swelling (angioedema), conjuctival swelling, periorbital edema

Respiratory

Occurs in up to 70%

Repeated coughing, chest tightness, wheezing, throat itching or throat swelling

Gastrointestinal

Occurs up to 45%

Nausea, vomiting, abdominal pain, diarrhea

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Signs and Symptoms of

Anaphylaxis (Cont.) Cardiovascular

Occurs in up to 45%

Dizziness, fainting, hypotension, tachycardia

Miscellaneous

Feeling of impending doom, confusion, anxiety

Metallic taste or swelling of tongue

At onset of episode, not possible to predict severity, rate

of progression, or whether biphasic or protracted

Biphasic and Protracted

Anaphylaxis

Biphasic

Symptoms reoccur after initial resolution of initial episode without additional exposure to trigger

Typically occurs 8 to 10 hours after resolution of initial symptoms

One third of secondary reactions more severe than initial response

Protracted

Reaction that lasts for hours, days, or even weeks in extreme cases

Requires prolonged observation

Observation

All patients should be observed for 12 hours prior to discharge after treatment of anaphylactic reaction due to risk of biphasic reaction

Patient Specific Risk Factors Co-morbidities or medications that interfere with

identification of triggers or symptoms

Vision or hearing impaired

Autistic spectrum disorder or other cognitive disorders

Psychiatric diseases

Sedatives or hypnotics

Recreational drugs or alcohol use

Patients at higher risk for fatal anaphylactic event

Underlying cardiovascular disease

Underlying pulmonary disease

Elderly patients with multiple disease states

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Patient Specific Risk Factors

Pregnancy

Associated with poor outcomes to fetus

Infants

Harder to recognize symptoms, mimic other benign

signs (eg, flushing, spitting up, loose stools)

Adolescents / Teenagers

Lack of concern about severity, not regularly carrying

epinephrine injector

At-Risk Environments Schools

1) Allergy awareness

2) Planning – creating individualized health plans

3) Allergen exposure avoidance measures

4) Treatment strategies

5) Training on what to do in the event of an anaphylactic event

Managing allergies in school is team effort encompassing health care provider, family, student, school

Cafeterias

Restaurants

Summer camps Busses

Social Outings

Prevention Primary method of prevention is identification and strict

avoidance of patient-specific triggers

Write it down

Information should be written and proved to each patient with known triggers as well as other probable cross-reactive triggers

Wear it

Carry ID (eg, medical alert, jewelry, wallet card) for identification so practitioners can quickly recognize and treat anaphylaxis

Be Prepared

Keep properly stocked emergency kit with prescribed medications available at all times

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Prevention (Cont.)

Use caution if allergic to stinging insects

Wear long-sleeved shirts, pants

Avoid bright colors, don't wear perfumes or colognes.

Stay calm if near stinging insect. Move away slowly,

avoid slapping at insect

Avoid wearing sandals or walking barefoot in grass

Anaphylaxis is Under

Recognized and Undertreated

Three diagnostic criteria now utilized

Developed in 2006

Each reflects different clinical presentation of

anaphylaxis

Anaphylaxis highly likely when any ONE of following

criteria fulfilled

Sampson HA et al. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium J Allergy Clin Immunol.

2006;117(2):391

Diagnostic Criteria Criterion 1

Acute onset of illness involving skin, mucosal tissue, or both (eg, generalized hives, pruritus, flushing, swollen lips-tongue-uvula) and at least one of the following:

Respiratory compromise

Reduced blood pressure (BP)

Criterion 2

Two or more of following that occur rapidly after exposure to likely allergen for that patient:

Involvement of skin-mucosal tissue (generalized hives, itch-flush, swollen lips-tongue-uvula)

Respiratory compromise

Reduced BP or associated symptoms and signs

Persistent gastrointestinal symptoms and signs

Criterion 3

Reduced BP after exposure to known allergen for that patient

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Treatment

Acute management of anaphylaxis is

same, regardless of trigger or mechanism

involved

Prompt epinephrine treatment is

recommended as first-line agent for

patients with anaphylaxis

Simmons KJ, Simmon ER. Epinephrine and its Use in Anaphylaxis: Current Issues. Curr Opin Allergy Clin Immunol. 2010;10(4):354 – 361

Mclean-Tooke AP, Bethune CA, Fay AC and Spickett, GP. Adrenaline in the treatment of anaphylaxis: what is the evidence? BMJ. 2003 December 6; 327(7427): 1332 - 1335

React Quickly…Staggering

Statistics Study that examined 164 patients with fatal

anaphylaxis found: 5 minutes was median time from initial symptom to

cardio-respiratory arrest

15 minutes in venom-triggered anaphylaxis

30 minutes in food triggered anaphylaxis

Delayed injection may contribute to biphasic anaphylaxis

Pumphrey RSH. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy. 2000; 30:1144-1150

Available Epinephrine Auto

Injectors in U.S.

EpiPen®

Adrenaclick®

Twinject®

Generic Epinephrine Auto Injector

Generic version of Adrenaclick.

EpiPen does not currently have generic available

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All Epinephrine Auto Injectors

are DIFFERENT

Epinephrine auto injectors are different and NOT

substitutable

To be trained on one, does not translate to

patient knowing how to use others

Epinephrine Auto Injectors

are BX Rated

FDA has BX rating for all epinephrine auto

injectors

Pharmacist must dispense named product and not

substitute one of the other injectors

Only “A”-rated (eg, AB rated) products considered

bioequivalent, and thus, substitutable

To date, there no “AB” rated epinephrine auto-injector

devices

Substitution laws regulated by state boards of pharmacy

Electronic Orange Book. Approved products with therapeutic equivalence evaluation. Current through March 2012. http://www.fda.gov/cder/ob/. (Accessed May 7, 2012). [For March 2012 full update].

Standard Doses for Epinephrine

Auto Injectors Doses

All devices use 1:1000 (1mg/ml) concentration of epinephrine

0.3 mg IM

For patients weighing 30kg or greater

If anaphylactic symptoms persist, dose may be repeated in 5-15 minutes

0.15 mg IM

For patients weighing 10 – 29 kg

if anaphylactic symptoms persist, dose may be repeated in 5-15 minutes

***Twinject is only available device that has option of giving second dose by manual injection

Dose should be repeated in 5 – 10 minutes if patient has a poor response to initial dose.

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How to use epinephrine auto

injectors

EpiPen Steps for use

Step 1: Remove safety cap

Step 2: Hold pen in fist. Do not put fingers at top or bottom of pen

Step 3: In one motion, Gently but FIRMLY put rounded tip hard into middle of the thigh and count for 10 seconds

Once pen is used call 911

Tip will extend upon use but Epipen has needle protected

AdrenaClick

Steps for use:

Step 1: Remove

GRAY cap

labeled “1”

Step 2: Remove

GRAY cap

labeled "2"

Step 3: Place RED tip on

middle of outer side of

thigh. Press down hard

until needle penetrates

skin and slowly count to

10

Step 4: Check

RED tip. If needle

exposed dose

received.

Dispose properly

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Twinject Twinject only available auto-injector that

provides 2 doses of epinephrine in 1 device May view video on use http://www.twinject.com

Twinject (Cont.) Second dose is manual injection

Positioning The Patient

Patients with anaphylaxis should not suddenly sit, stand,

or be placed in upright position

They should be placed on back with lower extremities

elevated

If they are experiencing respiratory distress or vomiting,

they should be placed in position of comfort with lower

extremities elevated

This accomplishes 2 goals:

Preservation of fluid in circulation

Prevention of empty vena cava/empty ventricle syndrome

May suddenly occur when patients with anaphylaxis

suddenly assume or placed in upright position

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Other treatment options…..

Antihistamines: H1 Class NOT A SUBSTITUTE for epinephrine

Slow in onset

DO NOT relieve air obstruction, hypotension or shock

CAN be used as adjunctive therapy to reduce severity of the following: Itching

Redness

Angioedema

Nasal and eye symptoms

Sheikh A, Ten Broek V, Brown SG, Simons FE.H1-antihistamines for the treatment of anaphylaxis: Cochrane systematic review Allergy. 2007;62(8):830

Antihistamines: H1 Class (Cont.)

For oral therapy, second-generation preferred in adults Fexofenadine at 180 mg/day

Children 2-11 years: 30 mg twice daily Loratadine at 10 mg/day

Children 2-5 years: 5 mg once daily

Cetirizine at 10 mg/day Children 6-23 months: 2.5 mg once daily

Children 2-5 years: 2.5 mg/day; may be increased to a maximum of 5 mg/day

Desloratadine at 5 mg/day

Levocetirizine at 5 mg/day

Diphenydramine may be used if IV therapy needed 25 – 50 mg IV per dose for adult

1mg/kg/dose up to 50mg (max per dose) in children (max 5mg/kg/day)

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H2-Antihistamines

Given concurrently with H1-antihistamine, may potentially help decrease flushing and headache Shown with ranitidine

Minimal evidence to support use in conjunction with H1-antihistamines in emergency treatment

Most guidelines do not include this class of agents

Simons FER. Advances in H1-antihistamines. N Engl J Med. 2004;351:2203–2217.

Bronchodilators

Albuterol (inhaled beta-2 adrenergic agonist)

Adjunctive treatment only

Minimal alpha-1 adrenergic agonist vasoconstrictor

effects

Does not prevent or relieve laryngeal edema, upper

airway obstruction, hypotension or shock

Inhaled beta-2 adrenergic agonists useful in

patients with bronchospasm

Lieberman P, Nicklas RA, Oppenheimer J, Kemp SF, Lang DM, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 Update. J Allergy Clin Immunol. 2010;126:477–480.

Corticosteroids

Have no immediate effect on anaphylaxis

May help to prevent potential biphasic

anaphylaxis if given early

May give additional benefit to those with

underlying asthma

Cochrane systematic review article concluded:

“No evidence for use of steroids in emergency

management of anaphylaxis”

Can neither support nor refute use of these drugs for this

purpose

Choo KJ, Simons E, Sheikh A. Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review. Allergy.

Oct 2010;65(10):1205-11

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Corticosteroids (Cont.) Prednisone commonly used

No proven best dose exists

Adult dosing: 20 - 60 mg po daily for 2 – 5 days

Pediatric Dosing: 0.5 - 1 mg/kg/day in divided doses for 2 – 5 days

Tapering not necessary unless patient taking steroids chronically

Methylprednisolone Adults dosing- 125 mg/day IV daily

Pediatric dosing- 1 mg/kg IV daily or divided into 2 doses

Lieberman P, Nicklas RA, Oppenheimer J, Kemp SF, Lang DM, Bernstein DI, Bernstein JA, Burks AW, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin

Immunol. 2010;126(3):477.

Pharmacist Counseling

Pharmacist Counseling

Extremely important

Less than 44% of patients able to demonstrate correct epinephrine self-administration technique

75% of health care professionals who teach use of these devices unable to demonstrate correct use

Goldberg A, Confino-Cohen R. Insect sting-inflicted systemic reactions: attitudes of patients with insect venom allergy regarding after-sting behavior and proper administration of epinephrine. J Allergy Clin Immunol 2000 Dec;106(6): 1184-9

Grouhi M, et al. Anaphylaxis and epinephrine auto-injector training: Who will teach the teachers? J Allergy Clin Immunol 1999 Jul;104 (1): 190-3

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ISMP Safety Alert 2011

What happened? Nurse injected thumb because he/she confused

epinephrine injector as being similar to Novolog Flex pen

Recommended All health care providers and patients should be

educated on proper use

Health care providers and patients look to pharmacists for guidance

Counseling Points for All

Patients

Teach patients how to use device

Pharmacists to keep trainers in pharmacy/hospital

Call or go online to each manufacture to request free demo

trainers

DVD’s for patient use also available

Educate patients when to use device

GIVE AS SOON AS POSSIBLE – DON’T DELAY

Give if known expose to allergen that caused reaction even if no

symptoms developed yet

Give if symptoms appear even if not for known exposure

Patients should not wait and instead give when symptoms are mild

Counseling Points Cont.…

Teach them to get new refills the same time every year.

Pick holidays (eg, New Years Day).

Teach patients to replace devices before expiring

Advise patients to always keep devices accessible

Review with patients if second dose should be given

Up to 20% of patients may require second dose of epinephrine

either due to persistent symptoms or biphasic reaction. Second

dose should be given in 5 – 10 minutes if patient has persistent

symptoms

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Counseling Points Cont.…

Advise Patients to Wear a Medical Alert Bracelet

Family members should also be trained

Pharmacists to train parents and children of appropriate age

Other caregivers (eg, grandparents, older siblings, day care providers)

should be trained as well

Many options (eg, bracelets, necklaces) designed for both young and

old, trendy or traditional. Search web for many varieties

Have brochures of potential items in pharmacy/hospital to hand out to

patients

Have wallet cards at pharmacy/hospital to distribute to patients

Personalized Plans

Patients should work with all healthcare

providers to develop comprehensive

personalized plan:

Include known triggers

Concomitant disease states

Current medications

Note that patients able to demonstrate use of

prescribed epinephrine auto injector

Update yearly, when replacing pens

Thank You