Bedside Clinical Question:
Can you consider a loop diuretic in a patient with a sulfa allergy due to the antibiotic trimethoprim-sulfamethoxazole (sulfa-containing antibiotic)?
Background:
Adverse drug reactions to sulfonamide antibiotics are common, with a reported incidence of up to 3 -6% of antibiotic prescription courses, but < 3% of those are true hypersensitivity reactions.
Unfortunately, hypersensitivity reactions to sulfonamide antibiotics can be severe, including Stevens-Johnson syndrome, and life-threatening. This is why so many of us stop when we see a “sulfa” allergy in our patients when trying to order other "sulfa" containing medications.
There are chemical differences between sulfonamide antibiotics and sulfonamide non-antibiotics. While both groups do have a sulfonamide component in common, there are crucial differences between the groups.
Answer:
Sulfonamide non-antibiotics do not contain 2 other structures thought to cause the hypersensitivity common to sulfonamide antibiotics.
Sulfonamide non-antibiotics are much less likely to cause severe reactions, and cross-reactivity between sulfonamide antibiotics and non-antibiotics is extremely rare.
Literature shows that these drugs can be safely used, especially in emergencies. These include carbonic anhydrase inhibitors (acetazolamide), loop diuretics (furosemide), thiazide diuretics, sulfonylureas, COX-2 inhibitors, and triptans.
However, some drugs that may cause cross-reactivity include sulfadiazine, sulfasalazine, dapsone, silver sulfadiazine cream, and possibly sulfonamide antiretrovirals such as amprenavir and fosamprenavir.
Conclusion:
“Sulfa” allergies can be misleading at times.
An allergy to a sulfonamide antibiotic may cause cross-reactivity with other sulfonamide antibiotics but rarely to sulfonamide non-antibiotics.
The evidence shows that sulfonamide non-antibiotics do not need to be considered contraindicated in those with a history of hypersensitivity to antibiotic sulfonamides.
When you consider giving the loop diuretic in this case, look at the patient's medication profile and see if they have tolerated other sulfonamide non-antibiotics, which most have (think hydrochlorothiazide and glipizide). This would help support tolerability. Also, monitor your patient closely for any signs of hypersensitivity if the decision is made to administer it.
As always, consider the severity of the reaction. If it is severe (true anaphylactic reaction), consider giving ethacrynic acid IV or PO in place of a sulfa loop diuretic.
Written by: Joanne C Routsolias, PharmD, RN, BCPS
Clinical PharmD Specialist - Emergency Medicine/Toxicology
References:
Wulf NR, Matuszewski KA. Sulfonamide cross-reactivity: is there evidence to support broad cross-allergenicity? Am J Health Syst Pharm. 2013 Sep 1;70(17):1483-94.
Johnson KK, Green DL, Rife JP, Limon L. Sulfonamide cross-reactivity: fact or fiction? Ann Pharmacother. 2005 Feb;39(2):290-301.
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. N Engl J Med. 2003 Oct 23;349(17):1628-35.