From the Guidelines
Sulfur allergies are often misunderstood, and true sulfur allergies are extremely rare, with most reactions being to sulfonamide antibiotics or sulfites, which are distinct chemical compounds containing sulfur atoms. When considering drug interactions, particularly with medications containing sulfur (sulfonamides), it is essential to understand that sulfonamide antimicrobials are structurally different from nonantimicrobial sulfonamides due to the presence of an aromatic amine group at the N4 position 1.
Key Points to Consider
- Sulfonamide non-antimicrobials, such as furosemide, certain diabetes medications, and some pain relievers, are generally safe to use in patients with a history of reactions to sulfonamide antibiotics 1.
- There is minimal concern for cross-reactivity between sulfonamide–nonantimicrobials in patients with histories of reactions to sulfonamide antibiotics, including the sulfone dapsone 1.
- For patients with a history of benign cutaneous reactions to sulfonamide antibiotics that occurred >5 years ago, a 1-step drug challenge with TMP-SMX can be performed when there is a need to delabel a sulfonamide antibiotic allergy 1.
- Sulfites in medications might trigger asthma attacks in sensitive individuals, and sulfonamide antibiotics may increase the risk of bleeding with warfarin, enhance hypoglycemic effects of diabetes medications, and cause hyperkalemia when combined with ACE inhibitors or potassium-sparing diuretics.
Recommendations
- Avoid stating a general "sulfur allergy" when informing healthcare providers about previous adverse reactions to medications, and instead, be specific about which drugs caused problems.
- If a reaction to sulfonamide antibiotics has occurred, avoid that specific class of medications, but consider the use of other sulfur-containing drugs under medical supervision.
- Always consult with a healthcare provider before taking any medication, especially if there is a history of adverse reactions to sulfonamide antibiotics or sulfites.
From the Research
Implications of Sulfur Allergy on Drug Interactions
- Sulfonamide allergies can result in various physical manifestations, with rash being the most frequently observed 2
- The potential for cross-reactivity of allergies to sulfonamide antimicrobials with nonantimicrobial sulfonamide medications is low, with data suggesting that substitutions at the N1 and N4 positions are the primary determinants of drug allergy instead of the common sulfonamide moiety 2, 3
- Cross-reactivity between sulfa antibiotics and nonantibiotics is rare, but can affect the pharmacologic and clinical management of patients with sulfa allergy 4, 5
Management of Sulfonamide Allergy
- For patients with an indication for a sulfonamide antimicrobial with a listed allergy, healthcare practitioners should adequately assess the allergic reaction to determine appropriate management 2
- Rechallenge and desensitization strategies may be appropriate for patients with delayed maculopapular eruptions, while alternative treatment options may be prudent for more severe reactions 2, 3
- Available evidence supports the cautious reintroduction of sulfonamide antibiotics via desensitization, which is usually well tolerated and should be considered in those with strong indications for trimethoprim-sulfamethoxazole and a reported sulfonamide allergy 3
Clinical Considerations
- Sulfonamide drug allergy is frequently encountered by the practicing clinician, with delayed rash being the most common clinical manifestation for sulfonamide antibiotics 3
- There is no current evidence to support avoidance of all non-antibiotic sulfonamides in those with a reported allergy to sulfonamide antibiotics, although certain scenarios require caution 3, 6
- Unfounded concerns of cross-reactivity between sulfonamide antibiotics and a variety of non-antibiotic-containing sulfonamide drugs can render pharmacotherapy unnecessarily difficult 6