LETTER TO THE EDITOR

Furosemide allergy in children: separating the factsfrom the myths

Tiffany J. Hwang & Kassa Darge

Received: 20 May 2013 /Revised: 1 June 2013 /Accepted: 3 July 2013# Springer-Verlag Berlin Heidelberg 2013

Sir,In radiology, furosemide (Lasix) is regularly used in diureticrenography and MR urography. Although we cannot recallencountering an allergic reaction during such a study, recent-ly we have been having increased discussion regarding thistopic because the sedation doctors are reluctant to administerfurosemide to patients with sulfa-antibiotic allergies. Wewould like the pediatric radiology community to be awareof the issue of furosemide allergy because it has not beenadequately addressed in the radiology literature. This willallow us to conduct informed discussions with our clinicalpartners and to make the right decisions.

Although allergy to furosemide is rare, the risk of cross-reactivity between sulfa-antibiotics (SA), which are thesecond most frequent causes of drug reactions, and sulfa-nonantibiotics (SNA), such as furosemide, has been longdebated. Allergy claims are based upon concerns regard-ing the common sulfonamide moiety [1]. The FDA-approved drug label for Lasix (furosemide) cautions thatin patients allergic to sulfonamides, Lasix may exacerbateor activate systemic lupus erythematosus. Adverse reac-tions to SAs include hypersensitivity syndrome reactions,severe skin reactions and type I reactions. However, theformer two are mediated by the oxidation of the N4arylamine, a structure not present in SNAs, and type Ireactions depend upon the N1 heterocyclic ring, also not

present in SNAs. Another study specifically demonstratedthat antibodies from SA-allergic patients’ serum did notbind to furosemide [2].

There have been two large clinical studies of sulfonamidecross-reactivity. A retrospective study of 20,226 patientsevaluated the risk of allergy with SNA or penicillin whentaken within 60 days after receiving an SA. The study founda higher risk for SNA allergy in patients with prior SAallergy than those without, with an adjusted odds ratio(AOR) of 2.8 (CI 2.1–3.7). However, the association waseven higher when evaluating for the risk of subsequentpenicillin allergy (AOR 3.9, CI 3.5–4.3). Comparing therisks of subsequent SNA allergy to the risks of subsequentpenicillin allergy in patients with prior SA allergy gave anAOR of 0.7 (CI 0.5–0.9), suggesting that SA allergy is aneven stronger risk factor for subsequent penicillin allergythan SNA allergy. Last, the study compared the risks ofSNA allergy between patients with prior SA allergy andthose with prior penicillin allergy, resulting in an AOR of0.6 (CI 0.5–0.8), indicating that the risk for subsequent SNAallergy increased more significantly with previous penicillinhypersensitivity than with previous SA allergy. The studyconcluded that sulfa-allergy associations are caused not bycross-reactivity, but by a general predisposition to allergicreactions [3]. In a separate prospective study of 94 adults in ahospital setting, the frequency of adverse reactions to SNAsin SA-allergic patients was characterized. Of the 52% ofpatients who received potentially cross-reactive drugs, noadverse effects were reported [4]. Together, these biochem-ical and clinical studies show no evidence for sulfonamidecross-reactivity.

We reviewed 33 available publications, which described49 cases of furosemide allergy in patients with a mean age of60.5 years, with males predominating. Congestive heart andrenal failure were the main indications, treated with dosesbetween 20 mg and 1,000 mg. Although none of the reported

Electronic supplementary material The online version of this article(doi:10.1007/s00247-013-2761-7) contains supplementary material,which is available to authorized users.

T. J. Hwang (*) :K. DargeDivision of Body Imaging, Department of Radiology,The Children’s Hospital of Philadelphia,Perelman School of Medicine, University of Pennsylvania,34th Street and Civic Center Boulevard,Philadelphia, PA 19104, USAe-mail: hwangt@email.chop.edu

Pediatr RadiolDOI 10.1007/s00247-013-2761-7

cases occurred during imaging studies, the administereddoses are comparable to those used in such studies (40 mgfor adults, 1 mg/kg for children).

It is of note that only one case was reported in 1969 in apediatric patient, age 7. This child was prescribed furose-mide every 12 h for persistent edema secondary to nephroticsyndrome and tolerated both oral and intravenous adminis-tration with no ill effect. With his last dose, the childcomplained of excruciating abdominal pain followed bycardiac and respiratory arrest within 1 min of intravenousfurosemide administration [5].

Two other loop diuretics, both containing sulfa-moieties,are available in the U.S. market: bumetanide and torsemide.Bumetanide has shown success in treating five furosemide-allergic patients and torsemide has been suggested as theloop diuretic of choice for heart failure [6]. These drugsmay be considered potential alternatives for furosemide-allergic patients.

We suggest that a physician consider the informationpresented in this short review when discussing for diagnosticimaging the question of cross-reactivity of furosemide withsulfa-antibiotics.

In addition to the references listed below, 47 additionalreferences, including all case reports and pertinent reviews,are provided online as supplementary material.

Conflicts of interest None

References

1. Johnson KK, Green DL, Rife JP et al (2005) Sulfonamide cross-reactivity: fact or fiction? Ann Pharmacother 39:290–301

2. Brackett C, Singh H, Block J (2004) Likelihood and mechanisms ofcross-allergenicity between sulfonamide antibiotics and other drugs con-taining a sulfonamide functional group. Pharmacotherapy 24:856–870

3. Strom BL, Schinnar R, Apter AJ et al (2003) Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonan-tibiotics. N Engl J Med 349:1628–1635

4. Hemstreet BA, Page RL 2nd (2006) Sulfonamide allergies and out-comes related to use of potentially cross-reactive drugs in hospital-ized patients. Pharmacotherapy 26:551–557

5. Rance CP (1969) Cardiac arrest after intravenous furosemide. Lancet1:1265–1266

6. Wargo KA, Banta WM (2009) A comprehensive review of the loopdiuretics: should furosemide be first line? Ann Pharmacother43:1836–1847

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