10/7/2011
Michelle Huber PharmD., CGP
Hospice of Siouxland
 Differentiate between true allergic response and drug side effects.
 Understand cross–sensitivity between opiates, sulfas, and penicillin drug classes.
 Describe alternative drug choices that can be made with patient allergies.
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 Obtain History
 Sensitivity reactions:  Example: Aspirin sensitivity
 Examples: vancomycin and morphine
 Associated with histamine release
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 Not allergic reaction
 Drug side effect
 Sulfonamide antibiotics
 Isotretinoin
 tetracyclines
 React to drugs with similar chemical structure.
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 T or F
 Compared to drugs taken orally, drugs that are either injected or applied to the skin are more likely to cause allergic reactions.
 Obtain history
 Allergic reactions: 4
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 Medications can cause many different types of skin reactions. This particular appearance is called a "fixed drug eruption". This type of reaction typically happens in the same location when the person uses the same medication again.
Updated by: Linda J. Vorvick, MD, Medical Director, MEDEX Northwest Division of Physician Assistant Studies, University of Washington, School of Medicine; Paula J. Busse, MD, Assistant Professor of Medicine, Division of Clinical Immunology, Mount Sinai School of Medicine, New York, NY. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medicalirector,A.D.A.M., Inc
Individual with a rash to ampicillin.

Updated by: Linda J. Vorvick, MD, Medical Director, MEDEX Northwest Division of Physician Assistant Studies, University of Washington, School of Medicine; Paula J. Busse, MD, Assistant Professor of Medicine, Division of Clinical Immunology, Mount Sinai School of Medicine, New York, NY. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc
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This drug rash was caused by Tegretol. Medications can cause many different skin reactions, with varying rashes.
Updated by: Linda J. Vorvick, MD, Medical Director, MEDEX Northwest Division of Physician Assistant Studies, University of Washington, School of Medicine; Paula J. Busse, MD, Assistant Professor of Medicine, Division of Clinical Immunology, Mount Sinai School of Medicine, New York, NY. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc
 T or F  A patient who has experienced an allergy to one drug, is more likely to experience allergic reactions to other drugs.
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 Is there any medicine you cannot take for any reason?
 Why was the medication prescribed?
 How long ago did the reaction occur?
 By what route did you receive the medication?
 What type of reaction occurred?
 When the drug was stopped, what happened?
 Did they treat the reaction with anything?
 Have you taken the medication/similar medication since then? What happened?
 Have you had the same reaction with a different drug?
 A patient with sulfa allergies may also react to:
 A. furosemide
 B. glyburide
 C. acetazolamide
 D. All of the above
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 Sulfonylarylamines
 Non‐sulfonylarylamines
 Sulfonamide‐moiety containing drugs
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 You should not use SSD cream in a patient who has an allergy to Bactrim DS?
 True or False
 Sulfonylarylamines
 Antibiotics
 Sulfadiazine
 Sulfamethoxazole
 Sulfapyridine
 Sulfisoxazole
 Contraindications include ophthalmic (sodium sulfacetamide), topical (silver sulfadiazine [SSD, Silvadene]), and vaginal products (triple sulfa, sulfanilamide)
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 Acetazolamide (Diamox)
 Brinzolamide (Azopt)
 Dorzolamide (Trusopt) Warning
 Methazolamide (Neptazane)
 Warning
 Labeling warns that due to severe reactions to sulfonamides, sensitizations may recur when a sulfonamide is readministered
regardless of route of administration.
 This warning includes the ophthalmic preparations (brinzolamide and dorzolamide) because they are absorbed systemically.
 Two case reports suggest a connection between an anaphylactic reaction with acetazolamide and sulfonamide allergy.
 Celecoxib (Celebrex)
 In case reports, celecoxib has been suggested to cross‐
react with other sulfonamides.
 Risk of cross reactivity between celocoxib and other sulfonamides is not greater than with placebo ‐ (Three meta‐analyses evaluations). 10
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 Which diuretic is safest to use in a patient with a 



sulfonamide/sulfa allergy?
A. Furosemide
B. Indapamide
C. Torsemide
D. Ethacrynic acid
 Bumetanide (Bumex)
 Furosemide (Lasix) Precaution
 Torsemide (Demadex) Contraindicated in patients allergic
to sulfonylureas
 Some sources recommend that if a diuretic is used in a patient with a history of
sulfonamide allergy, the first dose should be reduced and given under medical
supervision.
 Bumetanide and furosemide product labeling contain statements that patients may also be allergic to these drugs if they are allergic to sulfonamides.
 Torsemide is contraindicated in patients allergic to sulfonylureas because its chemical structure is a pyridine sulfonylurea.  Ethacrynic acid does not contain a sulfa group and is a possible alternative in sulfonamide‐allergic patients.
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 Sulfonylureas
 Chlorpropamide None
 Glimepiride (Amaryl) Warning
 Glipizide (Glucotrol) None
 Glyburide (DiaBeta, others) Warning
 Tolbutamide (Orinase) None  Tolazamide (Tolinase) None
 Chlorothiazide (Diuril) Contraindicated
 Chlorthalidone (Hygroton) Contraindicated
 Hydrochlorothiazide Contraindicated
 Indapamide (Lozol) Contraindicated
 Metolazone (Mykrox,Zaroxolyn)Warning
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 Sulfasalazine (Azulfidine) Contraindicated  Sulfasalazine is broken down in the gut into sulfapyridine and 5‐aminosalicylic acid (mesalamine)
 T or F  You can tell by the name of all drugs if they have a sulfa component.
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 Naratriptan (Amerge)  Sumatriptan (Imitrex)  T or F
 Drugs such as morphine sulfate and potassium bisulfite should not be taken by patients who had an allergic reaction to a sulfonadmide drug.
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 Medications containing Sulfur, sulfites, sulfates
 Example: morphine sulfate
 Sulfite reaction in patients with asthma
 Saccharin
 Part of tablet exipients
 Has a sulfonamide moiety
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 Which is the most commonly reported drug allergy?
 A. sulfa
 B. morphine
 C. penicillin
 D. A and C
 How old were you when the reaction occurred?
 Can you describe the reaction?
 When did the reaction occur? After the first dose?




After the tenth dose?
How was the penicillin administered? Orally? Intravenously?
Were you taking any other medications at the same time?
When the penicillin was stopped, what happened?
Have you since taken a penicillin, cephalosporin, carbapenem, or monobactam?
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 Immediate/accelerated or Type I reactions
 Within 1‐72 hrs
 anaphylactic
 Type II
 Increased RBC and PLT clearance by lymphoreticular
system, hemolysis
 Type III
 Serum sickness and tissue injury
 Type IV
 Contact dermatitis
 Idiopathic
 Maculopapular or morbilliform rash
 May progress to Stevens‐Johnson syndrome
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 The incidence of cross‐reactivity between penicillin 



and cephalosporins is
A. 10%
B. 50%
C. 25%
D. < 1 %
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 Incidence <1%  Penicillin G
 cefprozil (Cefzil)
 cefoxitin (Mefoxin)
 cefadroxil(Duricef)
 Amoxicillin  Cefotaxime (Claforan)
 ampicillin (Omnipen)
 ceftizoxime(Ceftizox)
 cefaclor (Ceclor)
 ceftriaxone (Rocephin)
 cephalexin(Keflex)
 cefpodoxime (Vantin)
 cephradine(Velosef)
 cefepime(Maxipime)
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 Incidence
 imipenem [Primaxin]
 meropenem [Merrem]
 ertapenem [Invanz]
 doripenem [Doribax])
 Aztreonam [Azactam]
 rare
 Type I reaction
 No penicillin
 No 1st generation cephalosporin
 May be able to use 2nd, 3rd, or 4th generation cephalosporin‐CAUTION
 No carbopenams or monobactams
 Skin testing and dose escalation is recommended
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 Patient allergic to morphine are more likely to 





experience an allergic reaction to: 1. hydromorphone
2. meperidine
3. methadone
4. oxycodone
A. 1 and 2 C. 3 and 4
B. 1 and 4 D. 1, 2, and 4
 Phenylpiperidines: meperidine (Demerol), fentanyl
(Duragesic, Actiq, Sublimaze), sufentanil (Sufenta), remifentanil (Ultiva)
 Diphenylheptanes: methadone (Dolophine), propoxyphene (Darvon)
 Morphine group: morphine, codeine, hydrocodone
(Vicodin, Lorcet), oxycodone (Percocet, OxyContin), oxymorphone (Numorphan), hydromorphone (Dilaudid), nalbuphine (Nubain),
butorphanol (Stadol), levorphanol (Levo‐Dromoran), pentazocine (Talwin)
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 Tramadol (Ultram)
 contraindicated in patients with opioid allergy per U.S.and Canadian product labeling .23,26 There is not good evidence for cross‐sensitivity of tramadol with opioids.
 However, experts recommend using tramadol only for patients who have mild reactions to opioids.  Tapentadol (Nucynta [U.S.])
 does not contain this same contraindication, but the FDA considers tapentadol structurally related to tramadol.27 Experts also suggest cautious use of tapentadol in patients with opioid allergy.
 Pseudoallergy




Itching
Flushing
Sweating
angioedema
 True allergy
 Hives, maculopapular rash, erythema multiforme, pustular




rash
Increased heart rate
Low blood pressure
Bronchospasm
angioedema
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 Which opiates are most commonly associated with 





pseudoallergy?
1. morphine
2. codeine
3. meperidine
4. oxycodone
A. 1 and 2 B. 1, 2 and 3
C. 1,2, and 4
D. 3 and 4
 Use of a higher potency opioid [Evidence level C; expert opinion].
 Start with a low dose [Evidence level C; expert opinion].18  Avoid parenteral administration, or slow the
administration rate [Evidence level C; expert opinion].2
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 Reaction: flushing, itching, sweating, hives, and/or mild hypotension
 Continue opioid
 Add antihistamine  Dose reduction 
[Evidence level C;expert opinion].
 rash, severe hypotension, bronchospasm,
angioedema
 Choose opiate in a different structural class
 Monitor patient closely
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 Skin reaction directly under patch
 These food allergies can be a concern with 




medications.
A. peanuts
B. eggs
C. soy
D. all of the above
E. A and B
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 Egg allergies
 FluMist
 Cleviprex
 Peanut allergies
 Combivent Inh
 Atrovent Inh
 Both contain soy lecithin

PHARMACIST’S LETTER / PRESCRIBER’S LETTER June 2010 ~ Volume 26 ~ Number 260601

PHARMACIST’S LETTER / PRESCRIBER’S LETTER April 2009 ~ Volume 25 ~ Number 250415

PHARMACIST’S LETTER / PRESCRIBER’S LETTER February 2006 ~ Volume 22 ~ Number 220201
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301. 
Strom BL, Schinnar R, Apter AJ, et al. Absence of cross‐reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med 2003;349:1628‐35. 
Brackett CC, Singh H, Block JH. Likelihood and mechanisms of cross‐allergenicity between sulfonamide antibiotics and other drugs containing a sulfonamide functional group. Pharmacotherapy 2004;24:856‐70. 
Slatore CG, Tilles SA. Sulfonamide hypersensitivity. Immunol Allergy Clin North Am 2004;24:477‐90. 
American Academy of Pediatrics. "Inactive" ingredients in pharmaceutical products: Update (subject review). 1997 (information current as of May 12, 2010). Available at: http://www.pediatrics.org/cgi/content/full/99/2/268. (Accessed May 12, 2010). 
Kelkar PS, Li JT. Cephalosporin allergy. N Engl J Med 2001;345:804‐9. 
Romano A, Gueant‐Rodriguez RM, Viola M, et al. Cross‐reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins. Ann Intern Med 2004;141:16‐22. 
Pichichero ME. A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin‐allergic patients. Pediatrics 2005;115:1048‐57. 26
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1991;11:635‐44. Middleton RK, Beringer PM. Anaphylaxis and drug allergies. In: Koda‐Kimble MA, Young LY, Kradjan WA, et al., eds. Applied Therapeutics: the clinical use of drugs. 8th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. Crabe Erush S. Narcotic allergy. P&T 1996;21:250‐2, 292
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