Many patients are labeled as having a “sulfa allergy”. This is typically going to be from a reaction to sulfa antibiotics (i.e. sulfamethoxazole). Sulfonylureas are one of the drug classes that have sulfonamides as part of their chemical structure so therefore a theoretical cross-reactivity is possible. An estimated 3 – 6% of the population are allergic to sulfonamide antibiotics. Therefore, concerns about cross-reactivity between the sulfonamide antibiotics and sulfonylureas have been raised. What’s the evidence say about taking sulfonylureas with a sulfa allergy?

The study called “Absence of Cross-Reactivity of Sulfonamides Antibiotics and Sulfonamides Nonantibiotics” reports an increased risk of allergy with sulfonamides, nonantibacterial agents, in a group with a history of sulfonamide antibiotic allergy. The study reports that 9.9% experienced an allergic reaction of 969 patients with sulfonamide antibody-mediated allergic reaction. The study reports that 1.6% experienced an allergic reaction of 19,275 patients without a sulfonamide antibody allergic reaction. The study reports an adjusted OR ratio of 3.9 for patients who have an allergic reaction to penicillin after a reaction for a sulfonamide antibiotic compared to those with no reaction. The study concluded that the association between hypersensitivity of sulfonamide antibiotics and subsequent allergic reactions to sulfonamide nonantibiotics is based on a predisposition to allergic reactions. Therefore, it is unclear that a sulfonamide antibiotic allergy places a patient at risk for sulfonamide nonantibiotics due to cross-reactivity or predisposition to allergic reactions.

The prospective observational study called “Sulfonamide Allergies and Outcomes Related to the Use of Potentially Cross-reactive Drugs in Hospitalized Patients” reports that patients who have allergic reactions to a sulfonamide have a low risk of cross-reactive allergic reaction and are able to receive sulfonamide nonantimicrobial agents.

Available data shows that there is a low risk of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. However, it is still unclear about the specific percent or the number of cross-reactivity rate. Health care professionals should aware of the cross-reactivity risk and monitor closely when prescribing and dispensing the sulfonamide products to a patient who has a history of sulfonamide allergic reaction. 

With the best evidence we have, I am typically comfortable with the use of sulfonylureas with a sulfa allergy. However, I would educate the patient that there may be a very small risk and this should be monitored closely, particularly in patients who have had a very severe reaction in the past. 

In addition, I would have a heightened awareness of patients who have had numerous, significant allergic reactions to many different medications as they may be more at higher risk of future allergic reactions in general. 

Article written by Su Myat, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP

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Wulf NR, Matuszewski KA. Sulfonamide cross-reactivity: is there evidence to support broad cross-allergenicity?. Am J Health Syst Pharm. 2013;70(17):1483‐1494. doi:10.2146/ajhp120291

Strom BL, Schinnar R, Apter AJ, Margolis DJ, Lautenbach E, Hennessy S, Bilker WB, Pettitt D.  Absence of Cross-Reactivity between Sulfonamide Antibiotics and Sulfonamide Nonantibiotics.  New England Journal of Medicine. 2003; 349(17):1628-1635.

 Hemstreet B.A., Page R.L. Sulfonamide allergies and outcomes related to use of potentially cross-reactive drugs in hospitalized patients. Pharmacotherapy. 2006;26:551–557. doi: 10.1592/phco.26.4.551. 

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