Is acetazolamide a sulfa (sulfonamide) medication?

Is Acetazolamide a Sulfonamide Medication?

Yes, acetazolamide is definitively a sulfonamide derivative, but it is a non-antibiotic sulfonamide with minimal cross-reactivity risk to sulfonamide antibiotics. 1

Chemical Classification

• Acetazolamide is classified as a "non-bacteriostatic sulfonamide possessing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamides" 1
• The FDA drug label explicitly states that "acetazolamide is a sulfonamide derivative" and lists hypersensitivity to sulfonamides as a contraindication, noting that "cross sensitivity between acetazolamide, sulfonamides and other sulfonamide derivatives is possible" 1

Critical Structural Differences

The key distinction is that sulfonamide antibiotics contain an aromatic amine group at the N4 position, which is the structural component responsible for allergic reactions—this is absent in non-antimicrobial sulfonamides like acetazolamide. 2

• This structural difference results in minimal cross-reactivity risk between antibiotic and non-antibiotic sulfonamides 2
• The historical term "sulfa allergy" has been incorrectly applied to all sulfonamide-containing compounds, creating confusion about actual cross-reactivity risk 3

Clinical Evidence on Cross-Reactivity

Real-world clinical data demonstrates that acetazolamide can be safely used in patients with reported sulfonamide antibiotic allergies:

• In a retrospective review of 27 patients with self-reported "sulfa allergy" who received acetazolamide, only 2 patients (7%) developed urticaria, while 10 patients (37%) had no allergic reaction whatsoever 4
• No patient in this series experienced a severe life-threatening allergic cross-reaction 4
• Three patients with severe skin rash histories from antibiotic sulfonamides were successfully treated with acetazolamide without adverse reactions 5

Important Safety Considerations

While cross-reactivity is minimal, acetazolamide itself can cause severe allergic reactions independent of antibiotic sulfonamide allergy:

• Stevens-Johnson syndrome and toxic epidermal necrolysis are listed as potential adverse effects of acetazolamide itself 6, 7
• These severe reactions may be associated with specific HLA types (such as HLA-B59) in certain populations 7
• The FDA contraindication for hypersensitivity applies to acetazolamide-specific reactions, not necessarily cross-reactivity with antibiotic sulfonamides 1

Practical Clinical Approach

For patients with reported sulfonamide antibiotic allergy who require acetazolamide:

• Determine the nature and severity of the prior reaction—life-threatening reactions (anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis) warrant extreme caution regardless of the causative agent 4
• Simple cutaneous reactions or predictable side effects (paresthesias, metallic taste) from antibiotics do not preclude acetazolamide use 4
• The risk-to-benefit ratio should guide decision-making, particularly in conditions like glaucoma where acetazolamide provides significant therapeutic benefit 6, 4

Common Pitfall to Avoid

Do not automatically withhold acetazolamide based solely on a patient's report of "sulfa allergy" without clarifying what medication caused the reaction and what type of reaction occurred. Many patients labeled with "sulfa allergy" can safely receive acetazolamide, and denying treatment based on this label alone may deprive patients of effective therapy 5