Sulfasalazine
Prescription ·Exploratory record · not publication-reviewed ·Updated July 13, 2026
A prodrug combining sulfapyridine and 5-aminosalicylic acid (5-ASA) linked by an azo bond, used for the treatment of mild-to-moderate ulcerative colitis and rheumatoid arthritis. Colonic bacteria cleave the azo bond, releasing the active 5-ASA moiety locally in the colon, while sulfapyridine is absorbed systemically.
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What the research says.
A quick, data-only summary. The full evidence, dosing, and sources are below.
A prodrug combining sulfapyridine and 5-aminosalicylic acid (5-ASA) linked by an azo bond, used for the treatment of mild-to-moderate ulcerative colitis and rheumatoid arthritis. NutriStack rates the supporting evidence as strong. Common adult dosing is UC: 3–4 g/day in divided doses (maintenance: 2 g/day); RA: 2–3 g/day in divided doses (as prescribed by your physician), though a prescriber sets the actual dose. With long-term use it can deplete folate. This profile indexes 10 sources.
The bottom line
Evidence rating strong. Most-documented uses: induction and maintenance of remission in ulcerative colitis, treatment of rheumatoid arthritis (dmard), anti-inflammatory effect on colonic mucosa. 10 sources indexed (1990–2025), with 0 interaction records on file.
How it works, mechanistically.
Core mechanism
Bacterial azoreductases in the colon cleave sulfasalazine into sulfapyridine and 5-ASA. The 5-ASA component acts locally as an anti-inflammatory agent by inhibiting cyclooxygenase and lipoxygenase pathways, reducing prostaglandin and leukotriene production, and scavenging free radicals. In rheumatoid arthritis, the intact molecule and sulfapyridine component contribute anti-inflammatory and immunomodulatory effects, although the exact mechanism in RA is not fully understood.1,2
Dosing & protocol.
Take with food or immediately after meals to reduce GI side effects; adequate fluid intake recommended; may discolor urine/skin orange-yellow
What it depletes.
Nutrients this medication can lower over time, and what to replace.
Folate
SignificantSulfasalazine impairs folate absorption in the small intestine and can lower folate status during chronic therapy.
Full safety detail.
Side effects
- Nausea and vomiting
- Headache
- Anorexia
- Skin rash
- Oligospermia (reversible)
- Hemolytic anemia (in G6PD deficiency)
- Hepatotoxicity (rare)
- Agranulocytosis (rare)
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Meta-analyses & systematic reviews
4- 1Meta-analysis and systematic review on Sulfasalazine/5-ASA use during pregnancy: Impact on neonatal and pregnancy outcomesPMIDAsthana R, Hamandi B, Brnabic A et al. · Reproductive toxicology (Elmsford, N.Y.) · 2025
Asthana R, Hamandi B, Brnabic A et al.. Meta-analysis and systematic review on Sulfasalazine/5-ASA use during pregnancy: Impact on neonatal and pregnancy outcomes. Reproductive toxicology (Elmsford, N.Y.). 2025
- 2Sulfasalazine and mesalazine for the maintenance therapy of Crohn's disease: a meta-analysisPMIDSteinhart AH, Hemphill D, Greenberg GR · The American journal of gastroenterology · 1994
Steinhart AH, Hemphill D, Greenberg GR. Sulfasalazine and mesalazine for the maintenance therapy of Crohn's disease: a meta-analysis. The American journal of gastroenterology. 1994
- 3Sulfasalazine revisited: a meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitisPMIDSutherland LR, May GR, Shaffer EA · Annals of internal medicine · 1993
Sutherland LR, May GR, Shaffer EA. Sulfasalazine revisited: a meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitis. Annals of internal medicine. 1993
- 4Meta-analysis of sulfasalazine in ankylosing spondylitisPMIDFerraz MB, Tugwell P, Goldsmith CH et al. · The Journal of rheumatology · 1990
Ferraz MB, Tugwell P, Goldsmith CH et al.. Meta-analysis of sulfasalazine in ankylosing spondylitis. The Journal of rheumatology. 1990
Reviews & position papers
2- 5A real-world pharmacovigilance study and pharmacological analysis of sulfasalazine based on the FDA adverse event reporting system (FAERS) databasePMIDGuo D, Tang B, Luo P et al. · Expert opinion on drug safety · 2025
Guo D, Tang B, Luo P et al.. A real-world pharmacovigilance study and pharmacological analysis of sulfasalazine based on the FDA adverse event reporting system (FAERS) database. Expert opinion on drug safety. 2025
- 6Safety assessment of sulfasalazine: a pharmacovigilance study based on FAERS databasePMIDYe W, Ding Y, Li M et al. · Frontiers in pharmacology · 2024
Ye W, Ding Y, Li M et al.. Safety assessment of sulfasalazine: a pharmacovigilance study based on FAERS database. Frontiers in pharmacology. 2024
Reference material
4- 7Smolen JS et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020.Source linkedPMID
- 8Ford AC et al. Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol. 2011.Source linkedPMID
- 9Plosker GL, Croom KF. Sulfasalazine: a review of its use in the management of rheumatoid arthritis. Drugs. 2005.Source linkedPMID
- 10Choi J, Patel P, Fenando A. Sulfasalazine. 2026Source linkedPMID
Common questions.
Quick answers about Sulfasalazine, drawn from the data on this page.
What is Sulfasalazine?
A prodrug combining sulfapyridine and 5-aminosalicylic acid (5-ASA) linked by an azo bond, used for the treatment of mild-to-moderate ulcerative colitis and rheumatoid arthritis. Colonic bacteria cleave the azo bond, releasing the active 5-ASA moiety locally in the colon, while sulfapyridine is absorbed systemically.
What is Sulfasalazine used for?
Commonly cited benefits of Sulfasalazine include: Induction and maintenance of remission in ulcerative colitis; Treatment of rheumatoid arthritis (DMARD); Anti-inflammatory effect on colonic mucosa; Disease modification in inflammatory arthritis. NutriStack rates the overall evidence as strong.
What is a typical dose of Sulfasalazine?
A typical adult dose of Sulfasalazine is UC: 3–4 g/day in divided doses (maintenance: 2 g/day); RA: 2–3 g/day in divided doses (as prescribed by your physician). The commonly recommended form is Tablet (immediate-release or enteric-coated). These are general ranges, not personalized advice; confirm the right dose with a clinician.
What are the side effects of Sulfasalazine?
Reported side effects include nausea and vomiting, headache, anorexia, skin rash, oligospermia (reversible), hemolytic anemia (in g6pd deficiency). This is educational information; check with a healthcare professional before use.
How strong is the evidence for Sulfasalazine?
NutriStack rates this as Strong, meaning multiple high-quality meta-analyses or systematic reviews converge on the same finding. Full tier criteria are at https://nutristackapp.com/methodology/evidence-tiers.
Use this with your stack
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