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Drug Allergies vs.
Pseudoallergies vs.
Expected Side Effects
Kaitlyn McDonald, PharmD
Pharmacy Practice Resident
Kootenai Health
March 6, 2016
Disclosures
• The author of this presentation has no conflicts of interest to
disclose.
Abbreviations
•
•
•
•
•
•
ACE – Angiotensin-converting enzyme inhibitor
ADR – Adverse drug reaction
COX – cyclooxygenase
IgE – immunoglobulin E
NSAID – non-steroidal anti-inflammatory
PCN – Penicillin
Learning Objectives
1. Recognize the difference between an allergy and an adverse
reaction
2. Demonstrate the ability to obtain an accurate patient allergy
history
3. Identify common adverse drug reactions to specific high
incidence medications
Drug Allergy
vs.
Pseudoallergy
Background
• ~250,000,000 people are treated in emergency departments
annually due to drug allergies
• Most common offenders:
• Aspirin
• Opioids
• Penicillins
• Sulfa drugs
Technician Tutorial: Drug Allergies. Pharmacist’s Letter 2009.
Ramifications
• Incorrect reporting of an “allergy” can mislead providers,
resulting in modification of treatment
• Alternatives will be given, which may not have the same
efficacy or therapeutic benefit, and may be more expensive
Signs & Symptoms of an Allergy
•
•
•
•
Swollen, red, itchy, rash
Hives (red, itchy patches)
Swelling of the face, tongue, lips and/or throat
Difficulty breathing or swallowing
What’s the difference?
Drug Allergy
• An over-reaction of the
immune system to a
foreign substance
Pseudoallergy
• Not caused by a direct
activation of the immune
system, instead
histamine is released
directly from
subcutaneous mast cells
• Mimics an allergic
reaction
What’s the difference?
Drug Allergy
• Anaphylaxis from
penicillin
• Stevens-Johnson’s
syndrome from
sulfonamides
•
•
•
•
Pseudoallergy
Red Man Syndrome from
vancomycin
Rash or hives after
radiocontrast media
Bronchospasm after aspirin
Angioedema and
anaphylaxis from ACE
inhibitors
Pathophysiology - Allergy
Medical Charting
• Record most pseudoallergies as an allergy
• Exception: reactions that occurred which can be
eliminated by a dose reduction or infusion rate change
• Red Man Syndrome
Drugs commonly
causing allergic
reactions
Penicillin
“My mom told me I’m allergic”
Penicillin
• ~10% of the population reports an allergy to PCN
• Skin Testing
• Skin-testing revealed that only ~10% of these patients had a
true PCN allergy
• Number of positive PCN test decreased by 10% each year
after allergic reaction
• After 10 years, 78% patients will have negative skin tests
Salkind AR, et al. JAMA 2001;285:2498-2505
Pullen H. Lancet 1967;1:1176-1178
Puchner TC, et al. Ann Allergy Asthma Immunol 2002;88:24-29
Solensky R. Ann Allergy Clin Immunol 2010;105:273
Penicillin
• Most common reactions:
• Uritcaria
• Pruritus
• Angioedema
• Incidence of a rash due to ampicillin is almost 100% if the
patient has a mononucleosis infection
• PCN are the drug of choice for certain infections, so avoiding
their use because of easy-to-treat adverse effects would be
inappropriate
Salkind AR, et al. JAMA 2001;285:2498-2505
Cross-Reactivity
• Beta-lactam family includes
•
•
•
•
PCN
Cephalosporins
Carbapenems
Azobactam*
*Azobactam has very weak
cross-reactivity with the other
beta-lactams.
http://textbookofbacteriology.net/antimicrobial_3.html
Frumin J, et al. Ann Pharmacother 2009;43:304-315
Cross reactivity
• Cephalosporins
• 1st & 2nd generation: ~5%
• 3rd & 4th generation: <1%
• Carbapenems
• ~1-10%
Frumin J, et al. Ann Pharmacother 2009;43:304-315
Solensky R, et al. Ann Allergy clin Immunol 2010;105:259-273
Pichichero ME. Pediatrics 2005;115:1048-1057
Desensitization
• Induces temporary tolerance to a drug
• Slow re-introduction of drug until induction of reaction (if any)
• Protocols for most antibiotics, aspirin, NSAIDS, chemotherapy,
sulfa, etc.
Sulfonamides
• Incidence is ~3%
• Most common reaction: maculopaular rash
• Usually develops after 7-14 days
• Severe reactions: Stevens-Johnson syndrome, toxic epidermal
necrosis, anaphylaxis
Cross-Reactivity
• Drugs that contain a sulfa moiety
• Simeprevir
• Amprenavir
• Fosamprenavir
• Sulfates, sulfites, sulfur
•
•
•
•
Morphine sulfate
Spironolactone
Ranitidine
Omeprazole
• No cross-reactivity between sulfa and any of these agents, but cannot
completely rule out the possibility for drugs with a sulfa moiety
Aspirin
• Most common reactions:
•
•
•
•
Asthma
Rhinorrhea
Urticaria
Angioedema
• COX-1 inhibition from aspirin and NSAIDs
• Blocks the production of prostaglandins which degranulate mast
cells
• Increase production of leukotrienes which cause
bronchoconstriction and increased mucus production
Stevenson DD, et al. Immunol Allergy Clin North Am 2004;24:491-505
Opioids
• True allergy is rare
• Codeine, morphine, meperidine
• Most common reactions:
• Pruritis
• Hallucinations
Opioids
• Allergic reaction or adverse drug event with a combo product
• Clarify with patient if they have tolerated any of the single agents
in the past
Non-Drug Allergies
• Food
• Soy & peanut (same family) – propofol, clevidipine
• Gluten – some tablet and capsule formulations
• Egg – flu vaccine (except recombinant flu vac)
Non-Drug Allergies
• Latex
• Incidence is ~2%
• More likely if allergy to avocado, kiwi, or banana
• Injectable vial stoppers, IV tubing, gloves
Pollart SM, et al. Am Fam Physician 2009;80:1413-1418
Non-Drug Allergies
• Dyes
•
•
•
•
•
Yellow No. 5
Yellow No. 6
Yellow No. 10
Red No. 40
Blue No. 2
• Most common reactions: contact dermatitis, rhinitis, urticarial,
bronchospasm, anaphylaxis
• Check with manufacturer if your patient has an allergy or ADR
to a dye that is not as common. Only the major culprits are
reported in package inserts.
American Academy of Pediatrics Committee on Drugs. Pediatrics 1985;76:635-642
Adverse Drug Reaction
vs.
Side Effect
What’s the difference?
Adverse Drug Reaction
• harmful or unpleasant
reaction as a result of
the administration of a
medication
Side Effect
• unintended effects that
can be either intolerable
or beneficial
Common or serious ADRs
• General Medication Classes
•
•
•
•
•
•
•
•
•
•
Chemotherapy agents – nausea or vomiting
Antibiotics – diarrhea, nausea
Opioids – pruritis, constipation, hallucinations, sedation
NSAIDs – peptic ulcer
Antipsychotics – weight gain, extrapyramidal symptoms
Statins – myopathy, rhabdomyolysis
Anti-insomnia agents – daytime somnolence
Anticoagulants – GI bleed
ACE inhibitors – cough, angioedema
Antacids (PPIs>H2Bs) – bone fractures
Common or serious ADRs
• Specific Medications
•
•
•
•
•
•
Isosorbide – headache
Digoxin – yellow vision
Fluoroquinolones – QTc prolongation
Acetaminophen – liver damage
Dabigatran – GI upset
Varenicline – nightmares
Taking a Patient
History
Recording an Allergy
Detail
Reason
Drug name
Include all active ingredients
Dose, frequency, route, infusion
rate
May be dose- or rate-related
Onset and offset of reaction
Helps determine causality and type of reaction
that occurred
Description of reaction and how
it was managed
Helps classify reaction as allergy or ADR
Allows the provider to use their clinical
judgment for further treatment plans
Reaction severity
Determines level of contraindication to the
medication and related agents
Original indication of drug
Rule out whether or not the reaction was
caused by the disease
Date of original (and most
recent) reaction
Mostly applicable to products that used to
contain contaminants or were animal-based.
We have much cleaner (less immunogenic)
products now
Patient Interview
•
•
•
•
•
•
Please describe the reaction.
How long ago did the reaction occur?
Have you ever had the same reaction with a different drug?
Have you ever tolerated similar drugs? (provide examples)
How soon after the reaction did the reaction occur?
How was the reaction managed?
Assessment
Questions
Assessment Question #1
Which of the following symptoms is classified as a
hypersensitivity reaction (allergy)?
A.
B.
C.
D.
E.
Cough
Bronchospasm
Hiccups
Nausea
Sedation
Assessment Question #1
Which of the following symptoms is classified as a
hypersensitivity reaction (allergy)?
A.
B.
C.
D.
E.
Cough
Bronchospasm
Hiccups
Nausea
Sedation
Assessment Question #2
You are reviewing a new patient’s allergies. The patient reports
that they are allergic to Penicillin. Which of the following
questions will provide you with further relevant information?
A. What type of reaction did you experience?
B. How long ago did the reaction occur?
C. What is the name of the doctor who prescribed you the
medication you had a reaction to?
D. A & B only
E. All of the above
Assessment Question #2
You are reviewing a new patient’s allergies. The patient reports
that they are allergic to Penicillin. Which of the following
questions will provide you with further relevant information?
A. What type of reaction did you experience?
B. How long ago did the reaction occur?
C. What is the name of the doctor who prescribed you the
medication you had a reaction to?
D. A & B only
E. All of the above
Assessment Question #3
Which of the following common medication - adverse drug
reaction matches does not belong?
A.
B.
C.
D.
E.
Inhalers – peptic ulcer
Opioids – constipation
ACE inhibitors – cough
Antipsychotics – weight gain
Chemotherapy agents – nausea
Assessment Question #3
Which of the following common medication - adverse drug
reaction matches does not belong?
A.
B.
C.
D.
E.
Inhalers – peptic ulcer
Opioids – constipation
ACE inhibitors – cough
Antipsychotics – weight gain
Chemotherapy agents – nausea