3/11/2011

Drug Allergies and

Cross Reactivities
Steven Blanner, PharmD, BCPS Disclosure

No conflicts of interest to report

• Explain the differences between a drug • ADR: any noxious, unintended, and undesired
allergy and an adverse drug reaction effect of a drug that occurs at doses used in
humans for prevention, diagnosis, or treatment
• Explain the most likely classes of – Predictable
medications
di ti involved
i l d in
i cross reactivity
ti it • Dose dependent
• Related to known pharmacologic actions of the drug
• Discuss ways to prevent possible drug
• Occur in otherwise normal patients
allergies – Unpredictable
• Dose independent
• Unrelated to the pharmacologic action
• Occur only in susceptible patients

Allergic Reaction • Pseudoallergic reaction: adverse drug effects

1. Immunologically mediated
2. Exhibits specificity
3. Recurrence on re-exposure
not proven to be immune mediated but resemble
allergic reactions in clinical presentation
• Drug Intolerance: a low threshold to the normal
pharmacologic action of a drug
• Anaphylaxis: an acute, life threatening allergic
reaction involving multiple organ systems
• Anaphylactoid reaction: synonym for pseudo
allergy; resembles anaphylaxis but does not
involve the immune system

1

• Penicillin antibiotics
– The most prevalent medication allergy
– 10% of all patients claim to be penicillin
allergic
– Of the 10% with reported penicillin allergy,
90% were found NOT to be allergic and were
able to tolerate penicillin
– Most common true reactions are urticaria,
pruritis, and angioedema
• Exact incidence of cross reactivity between
penicillins and cephalosporins is controversial
– 1960’s: High incidence, mainly due to lack of proven true
allergy and contaminated preparations
– 1970’s:
1970’ A Approximately
i t l 8% off patients
ti t with
ith penicillin
i illi allergy
ll
showed cross reactivity with cephalosporins
– Today: Reports range from less than 1% to 3%
• Cross reactivity between penicillins, cephalosporins,
and carbapenems is reported to be between 6-47%
• Cross reactivity between penicillins and
monobactams is virtually non-existent
• Sulfonamide antibiotics/non-antibiotics
– Approximately 3-5% of patients report being allergic to
sulfonamide antibiotics, mainly Bactrim
– 2% of patients receiving a non-antibiotic sulfonamide
have reported an allergy
– Non-antibiotic sulfonamides include bumetanide,
furosemide, glimepiride, glipizide, glyburide, HCTZ,
probenecid, and torsemide
3/11/2011
• Possible cross reaction may occur with
other  lactam antibiotics
– Cephalosporins
– Carbapenems
C b
– Monobactams (aztreonam)
• Likelihood dependent on R side chains
• Choosing an appropriate antibiotic
– Patients who experience an ADR (nausea,
vomiting, malaise, dizziness, etc) with
penicillins can be treated with another
penicillin or use an alternative antibiotic
– Patients with a true penicillin allergy should
NOT receive penicillins.
– Using a cephalosporin with a dissimilar side
chain than penicillin is possible.
• Cross reactivity between sulfonamide antibiotics and
non-sulfonamide antibiotics is relatively uncommon
• Data suggest risk of cross reactivity reflects a general
heightened risk of allergic reactions rather than a specific
cross reactivity
• In general, patients with a history of sulfonamide
antibiotic allergy don’t need to avoid all sulfonamide
compounds
2

• Opioids
– True opioid allergy is rare
– The most common type of reaction is pseudoallergy
• Symptoms can resemble a true allergy, but are caused by histamine
release from mast cells
• Most common symptoms are itching, flushing, & sweating
• Prior exposure to opioid is not required
• Guilty parties: codeine, morphine, meperidine
– True opioid allergies usually involves hives, maculopapular rash,
erythema multiforme, pustular rash, bronchospasm, and
angioedema
• Patients that have a true allergy are
thought to be less likely to react to an
opioid in a different structural class
• Patients
P ti t can experience
i a true
t allergy
ll tto
multiple opioid classes
• Local Anesthetics “-caines”
– True allergies to local anesthetics is uncommon
– Anaphylaxis is extremely rare
– Most reactions are vasovagal, psychogenic, toxic, or a
predictable side effect of the epinephrine that
commonly is included in the preparation
– Other possible causes include the preservatives in
multidose vials
– Patients can be labeled allergic and told to avoid all “-
caines”, which is not necessarily true
3/11/2011
• Three main opioid structural classes
– Morphine group: morphine, codeine,
hydrocodone, oxycodone, hydromorphone,
nalbuphine, butorphanol, pentazocine
nalbuphine butorphanol
– Diphenylheptanes: methadone, propoxyphene
– Phenylpiperidines: meperidine, fentanyl,
sufentanil, remifentanil
• Choosing an appropriate opioid
– If reaction only resembles symptoms associated with
pseudoallergy, the opioid can usually be continued
• Dose reduction or antihistamine may be warranted
• Start with a low dose or use a more potent opioid
• Slow administration rate if parenteral
– If reaction resembles a true allergic reaction (rash,
hypotension, bronchospasm, angioedema), choose another
opioid in a different structural class and monitor patient
• Two major classes of local anesthetics
– Benzoate esters: benzocaine, chloroprocaine, cocaine, procaine,
proparacaine, tetracaine
– Amides: bupivicaine, dibucaine, lidocaine, prilocaine, ropivacaine
• Cross reactivity only exists among the benzoate esters,
not the amides
• If the patient has experienced a true allergy to a
benzoate ester local anesthetic, an amide may be
considered
• If the patient experienced a true allergy to an amide,
another amide or a benzoate ester may be considered
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• Radiocontrast agents • Seafood and Shellfish

– Incidence of reaction to radiocontrast is
between 5% to 8.5% of procedures
– Allergic reactions occur in 1% of patients who
receive contrast media
– Older, high-osmolar agents have a greater
frequency of reactions compared to the new,
lower-osmolar agents
– Risk of reaction is greater in women and
patients with a history of atopy or asthma
• Cross-reactivity between seafood or shellfish and
radiocontrast agents is a common misconception
– The thought was that both seafood/shellfish and some
radiocontrast agents contained iodine, which was responsible for
causing
i theh allergic
ll i reaction
i
– Shellfish or seafood allergy is related to the proteins found in the
meat of the fish – iodine plays no etiologic role
• A seafood or shellfish allergy does not predispose to
radiocontrast reactions
• Patients with a seafood/shellfish allergy are not at an
increased risk of reaction to radiocontrast agents

• Basic principles • Avoid offending agents

– Discontinue the medication when possible • A thorough history is essential in evaluating
– Treat adverse clinical signs and symptoms patients
• Antihistamines – What
a is
s the
e name
a eo of the
eddrug?
ug
• Corticosteroids
– How long ago did this occur?
• Anaphylaxis requires urgent care
– What were the characteristics/systems involved?
– Epinephrine
– At what point during treatment did the reaction occur?
– Oxygen
– Fluids – How was the reaction managed?
– BP support – Had the patient taken the same or cross reacting
– Antihistamines, corticosteroids medication prior to the reaction?
– Has the patient been re-exposed?
– Substitute another agent if necessary

• Adverse reactions are common

• True allergic reactions must be immune sblanner@srhc.com
mediated
• Be aware of cross reactions between
– Penicillins, Cephalosporins, Carbapenems
– Sulfonamides
– Opioids
– Local anesthetics
• Seafood/shellfish allergy ≠ Radiocontrast allergy

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 3/11/2011

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