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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