Dr William Smith, one of the authors of the article, comments:
The essential question is whether a patient who has a history of an allergic reaction to a sulfonamide antibiotic (sometimes inappropriately referred to as 'sulfur allergy') is at increased risk of an allergic reaction to acetazolamide compared to a patient with a history of allergy to an unrelated drug, or with no drug allergy history.
It is known that being allergic to one drug increases the risk of allergy to other drugs, regardless of the structural difference or similarity of the second drug. In fact the more drugs one is allergic to, the greater the risk that one will have a reaction to any other drug. This is a separate issue to cross-reactive allergy, which depends on the structural relatedness of the drug, such that the immune system, primed to respond to one drug, will react with a second structurally similar drug.
Firstly, acetazolamide, although a sulfonamide, is not a sulfonylarylamine sulfonamide and is therefore thought to be not sufficiently structurally similar to sulfonamide antibiotics to be cross-reactive to the immune system. Secondly, a survey of patients with a history of sulfonamide antibiotic allergy did not show an increased incidence of allergic reactions to non-antibiotic sulfonamides (including acetazolamide) above that conferred by a history of allergy to unrelated drugs.1
The patient who had anaphylaxis to acetazolamide constitutes anecdotal evidence. It is most likely that this allergic reaction was coincidental and not specifically related to a previous history of allergy to sulfonamide antibiotics.
Current expert opinion, based on the evidence, would be that a history of sulfonamide antibiotic allergy should not be considered an absolute contraindication to the use of acetazolamide. (I acknowledge that this is contrary to the current product information; it would be wise for medicolegal reasons to employ caution in such patients.) Doctors should always be prepared to deal with allergic reactions to the medications they prescribe, although these reactions are rare. Intravenous drugs carry a risk of causing more severe anaphylaxis although not at any greater incidence compared with oral administration. The risk of such reactions will be increased above background levels in patients with a history of allergy to other drugs, particularly multiple other drugs, whether sulfonamide or not.