Post on 22-May-2020
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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