Is sulfasalazine a sulfonamide (sulfa) drug?

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From the Guidelines

Yes, sulfasalazine is a sulfa drug, as it contains a sulfa component (sulfapyridine) linked to 5-aminosalicylic acid (5-ASA or mesalamine), making it a member of the sulfonamide class of medications. This classification is crucial for clinical practice, especially when considering patients with known sulfa allergies, as they may be at risk of allergic reactions ranging from mild skin rashes to severe reactions like Stevens-Johnson syndrome 1. Sulfasalazine is commonly used to treat inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, as well as rheumatoid arthritis. The medication's efficacy in reducing inflammation is attributed to both its 5-ASA component, which acts locally in the intestines, and the sulfapyridine component, which is absorbed systemically and provides additional anti-inflammatory effects 1.

When prescribing sulfasalazine, healthcare providers typically initiate treatment with a low dose (500 mg daily) and gradually increase to the therapeutic dose (usually 2-4 grams daily divided into multiple doses) to minimize side effects like nausea and headache. It's also important to note that sulfasalazine can interfere with folic acid metabolism, and patients are often recommended to take folate supplementation. Given its potential for side effects, including rare but serious cutaneous and hematologic reactions, laboratory monitoring of complete blood counts and liver function tests is necessary for patients on sulfasalazine 1.

Key points to consider in the management of patients with sulfasalazine include:

  • Starting with a low dose and gradually increasing as tolerated to minimize side effects.
  • Monitoring for signs of allergic reactions, especially in patients with known sulfa allergies.
  • Providing folate supplementation due to the drug's effect on folic acid metabolism.
  • Regular laboratory monitoring for potential hematologic and hepatic adverse effects.
  • Considering alternative treatments, such as mesalamine or balsalazide, which may have better tolerability profiles for some patients 1.

Overall, while sulfasalazine is an effective treatment option for certain conditions, its use must be carefully considered and monitored due to its potential for adverse effects and its classification as a sulfa drug.

From the FDA Drug Label

A study of 1,455 pregnancies associated with exposure to sulfonamides indicated that this group of drugs, including sulfasalazine, did not appear to be associated with fetal malformation. Sulfonamides, including sulfasalazine, are present in human milk

Sulfasalazine is a sulfonamide (sulfa) drug. This is directly stated in the drug label as it mentions sulfasalazine in the context of sulfonamides 2.

From the Research

Sulfasalazine Classification

  • Sulfasalazine is classified as a non-antibiotic sulfonamide 3
  • It is structurally related to antibiotic sulfonamides, which may lead to cross-reactivity in patients with hypersensitivity to these drugs 3
  • Sulfasalazine is composed of mesalazine and sulfapyridine linked by an azo bond, with the clinical activity derived from the mesalazine moiety 4

Chemical Structure and Metabolism

  • Sulfasalazine is metabolized by intestinal bacteria, resulting in the release of sulfapyridine and 5-aminosalicylate 5
  • The drug's mechanism of action may relate to its effects on prostaglandin synthesis or interference with arachidonic acid metabolism by the lipoxygenase pathway 5

Cross-Reactivity with Other Sulfonamides

  • Patients with hypersensitivity to sulfasalazine may also react to other sulfonamides, such as sulfamethoxazole, due to cross-reactivity 3
  • This cross-reactivity is dependent on chemical features rather than the indication of the drugs 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cross-reactivity in drug hypersensitivity reactions to sulfasalazine and sulfamethoxazole.

International archives of allergy and immunology, 2010

Research

Pharmaceutic development: mesalazine.

Scandinavian journal of gastroenterology. Supplement, 1990

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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