Are Cox-2 (cyclooxygenase-2) inhibitors, nitrofurantoin, diuretics, glyburide (Glibenclamide), glipizide, dapsone, and sulfasalazine classified as sulfa drugs?

From the Guidelines

Several of the medications mentioned, including Cox-2 inhibitors, certain diuretics, glyburide, glipizide, dapsone, and sulfasalazine, are indeed sulfa drugs, while nitrofurantoin is not. These medications can be classified as sulfa drugs due to the presence of a sulfonamide group in their chemical structure. According to the most recent evidence from 1, Cox-2 inhibitors like celecoxib, certain diuretics such as thiazide and loop diuretics (e.g., hydrochlorothiazide and furosemide), and sulfonylureas (e.g., glyburide and glipizide) are listed as sulfonamide non-antimicrobials with no or weak evidence of cross-reactivity in patients with a history of sulfonamide antimicrobial adverse reactions. Some key points to consider include:

• Cox-2 inhibitors, such as celecoxib, contain a sulfonamide group, as noted in 1.
• Nitrofurantoin is not a sulfa drug, despite being an antibiotic.
• Diuretics, including thiazide and loop diuretics (e.g., hydrochlorothiazide and furosemide), are sulfonamide derivatives.
• Glyburide and glipizide, which are sulfonylureas used for diabetes treatment, contain sulfonamide structures.
• Dapsone and sulfasalazine are definitely sulfa drugs, with sulfasalazine containing a sulfonamide component called 5-aminosalicylic acid linked to sulfapyridine, as mentioned in 1. It is essential to consider the potential for allergic reactions in patients with sulfa allergies when prescribing these medications, although the risk varies between different classes of sulfonamide-containing drugs. The chemical structure of these medications, including the SO2NH2 (sulfonamide) group, is responsible for their classification as sulfa drugs and is the molecular basis for potential cross-reactivity in patients with sulfa allergies. In clinical practice, it is crucial to weigh the benefits and risks of using these medications in patients with a history of sulfa allergies, taking into account the severity of the allergy and the potential consequences of an adverse reaction. As noted in 1, there is minimal concern for cross-reactivity between sulfonamide non-antimicrobials in patients with histories of reactions to sulfonamide antibiotics, including the sulfone dapsone. However, it is always best to exercise caution and consider alternative treatment options when possible.

From the FDA Drug Label

The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides), and oral hypoglycemic agents Cross-sensitivity may exist with these agents.

• Sulfasalazine is a sulfa drug.
• The other medications listed (Cox-2 inhibitors, nitrofurantoin, diuretics, glyburide, glipizide, dapsone) may have cross-sensitivity with sulfonamides, but the label does not explicitly state they are sulfa drugs.
• Diuretics (acetazolamide and the thiazides) are mentioned as having chemical similarities to sulfonamides, but it is not clear if all diuretics are sulfa drugs.
• Oral hypoglycemic agents are also mentioned as having chemical similarities to sulfonamides, but it is not clear if all oral hypoglycemic agents (such as glyburide and glipizide) are sulfa drugs 2.

From the Research

Sulfonamide Cross-Reactivity

The question of whether certain drugs, including Cox-2 inhibitors, nitrofurantoin, diuretics, glyburide, glipizide, dapsone, and sulfasalazine, are sulfa drugs and the potential for cross-reactivity with sulfonamide antibiotics is complex.

• Cox-2 inhibitors are considered sulfonamides due to their chemical structure, as are diuretics and certain anti-diabetic drugs 3.
• The risk of cross-reactivity between different sulfonamides is not clearly established, with some studies suggesting that the sulfonamide group itself may not be the primary cause of hypersensitivity reactions 4, 5, 6.
• Data suggests that substitutions at the N1 and N4 positions of the sulfonamide molecule are more important determinants of drug allergy than the presence of the sulfonamide group alone 5, 7.
• There is limited evidence to support broad cross-allergenicity between antibacterial and nonantibacterial sulfonamide agents, with most case reports of possible cross-reactivity lacking adequate patient testing to confirm sulfa allergy or sulfonamide cross-sensitivity 7.

Specific Drugs

• Diuretics, such as loop and thiazide diuretics, are structurally related to sulfonamides but do not exhibit the same features associated with sulfonamide reactions 7.
• Glyburide and glipizide are sulfonylureas, which are nonantibacterial sulfonamides, but the risk of cross-reactivity with sulfonamide antibiotics is considered low 5, 7.
• Dapsone and sulfasalazine are sulfonamide-type drugs, but the potential for cross-reactivity with other sulfonamides is not well established 4, 6.
• Nitrofurantoin is not typically considered a sulfonamide, but its chemical structure is distinct from that of sulfonamide antibiotics 4.

Clinical Implications

• The decision to use or avoid certain drugs in patients with a history of sulfonamide allergy should be individualized, taking into account the specific drug and the patient's medical history 4, 3, 6.
• Desensitization protocols may be a viable option for patients who require treatment with a sulfonamide antibiotic but have a history of allergy 4, 6.