On the other side, small studies reveal little risk of cross-reaction
Researchers involved in a retrospective study of 363 hospital charts examined 34 patients with a self-reported history of sulfa allergy who were subsequently given acetazolamide (a carbonic anhydrase inhibitor), furosemide (a loop diuretic), or both.2 The nature of the self-reported sulfa allergic reaction was documented in 79% of the 34 patients. These reported reactions included urticarial rash, nonspecified rash, dyspnea, swelling, nausea or vomiting, throat swelling, red eyes, and bullae. Two patients who were given acetazolamide developed urticaria. No allergic reactions occurred for those patients given furosemide.
The researchers concluded that there was little clinical or pharmacological evidence to suggest that a self-reported sulfa allergy was likely to produce a life-threatening cross-reaction with acetazolamide or furosemide. Small numbers and the lack of a standard definition for an allergic reaction limited the strength of their conclusion.
A small single-blind study of 28 patients with a history of fixed drug eruption to sulfonamide antibiotics examined the usefulness of patch testing as an alternative to controlled oral challenge testing.3 Before patch testing, a sulfonamide antibiotic allergy was confirmed by each patient with an oral challenge of sulfamethoxazole, sulfadiazine, or sulfamethazole. Potential cross-reactivity to several nonantibiotic sulfonamides (including furosemide) was also investigated using controlled oral challenge testing of these agents. Every patient tolerated a subsequent oral challenge with furosemide.
Literature reviews limited by small numbers
Two literature reviews examined the small number of case series, case reports, and “other articles” and concluded little evidence supports the presence of cross-reactivity between sulfonamide antibiotics and non-sulfonamide antibiotics.3,4 These reviews were limited by their search criteria and lack of explicit critical appraisal.
A literature review of Medline from 1966 to early 2004 revealed 21 case series, case reports, and “other articles” that evaluated the presence of cross-reactivity.3 When the authors of this literature reviewed drilled down to diuretics, they found 5 case reports for cross-reactivity to acetazolamide, 2 case reports for furosemide, 1 case series, and 2 case reports for indapamide (a thiazide diuretic). After reviewing the studies, the authors concluded that little evidence suggested a problem with cross-reactivity either with acetazolamide or furosemide and that there may be an association of cross-reactivity between sulfonamide antibiotics and indapamide. This study was limited by its small numbers and lack of explicit critical appraisal.
In another literature review—in which the main focus was cross-reactivity between sulfonamide antibiotics and celecoxib—the authors concluded that little evidence supported definitive cross-reactivity between sulfonamide antibiotics and diuretics.4 The limitations of this study were similar to those of the previous study.
Recommendations from others
The manufacturer insert for furosemide states, under the heading “General Precautions,” that “patients allergic to sulfonamides may also be allergic to furosemide.”5 A similar warning occurs for hydrochlorothiazide under the heading “Contraindications.”6