Furosemide (Lasix) is a member of the general class of loop diuretics that inhibit the Na+/K+/2Cl-cotransport carrier within the ascending limb of the loop of Henle.
Lasix is known to cause Sulfa allergy. The decrease in sodium and chloride reabsorption seems to come from the fact that furosemide competes for the chloride position on the carrier.
Although all loop diuretics have the same primary mechanism of action, furosemide has been shown to additionally inhibit sodium and chloride reabsorption in the distal renal tubule.
It is important to note the additional decrease in calcium reabsorption because calcium transport in the loop of Henle is directly related to the gradient established by the movement of sodium and chloride. It has a wide range of clinical uses including treatment of hypertension, congestive heart failure, and hyperkalemia.
Signs and Symptoms of sulfa allergy
Clinically, a controversial issue in the administration of furosemide is the incidence of cross-reactivity with sulfonamide-containing antibiotics because of the sulfonamide moiety that furosemide contains. The clinical issue centers on the administration of furosemide to a patient with documented sulfa allergy.
Opinions differ on the believed hypersensitivity cross-reaction that may manifest itself as anaphylaxis, dermatitis, urticaria, eczema, Stevens-Johnson syndrome, rash, or fever within 30 days, but current literature states that the lack of published clinical evidence for the allergic reactions is noteworthy.
The authors of a recently published review of the literature on this topic state that much of the evidence used to provide support for the theory is in fact not conclusive and does not implicate appropriate causation.
Detractors of the belief of a legitimate cross-reactivity also cite that sulfonamide nonantibiotics lack the aromatic amine group at the N4 position of sulfonamide-containing antibiotics, believed to be the cause of sulfonamide antibiotic hypersensitivity.
A retrospective study was performed to determine if furosemide produced allergic cross-reactions in patients who reported sulfa allergies. The authors did not find sufficient evidence to implicate a reported sulfa allergy in producing severe reactions.
It is also the opinion of some authors that the risk of reactions is so low that if alternative nonsulfa treatments are unavailable, administration of a drug such as furosemide with monitoring is warranted. Physicians who wish to provide an alternate drug to patients about whom they may be concerned could consider ethacrynic acid, a loop diuretic that does not contain a sulfa moiety.
Lee A, Anderson R, Kardon R, et al. Presumed sulfa allergy in patients with intracranial hypertension treated with acetazolamide or furosemide: cross reactivity, myth or reality? Am J Ophthal 2004;138.
Johnson K, Green D, Rife J, et al. Sulfonamide cross-reactivity: fact or fiction? Ann Pharmacother 2005;39.
Sullivan TJ. Cross-reactions among furosemide, hydrochlorothiazide, and sulfonamides [Letter]. JAMA 1991