What is sulfasalazine?

Sulfasalazine: A Comprehensive Overview

Sulfasalazine is an anti-inflammatory medication primarily used to treat inflammatory bowel disease (particularly ulcerative colitis) and rheumatoid arthritis, consisting of 5-aminosalicylic acid (5-ASA) linked to sulfapyridine by an azo bond. 1

Mechanism of Action

• Sulfasalazine functions as a prodrug that is cleaved by colonic bacteria at the azo bond, releasing its two active components: 5-aminosalicylic acid (5-ASA) and sulfapyridine 1, 2
• The 5-ASA component is believed to be the primary active moiety for treating ulcerative colitis, acting locally in the colon with minimal systemic absorption 1, 2
• Sulfapyridine is well absorbed from the colon (approximately 60% bioavailability) and may contribute to both local and systemic effects 1
• The exact mechanism of action remains under investigation but is thought to involve anti-inflammatory and immunomodulatory properties 1, 3

FDA-Approved Indications

• Treatment of mild to moderate ulcerative colitis 1
• Adjunctive therapy in severe ulcerative colitis 1
• Prolongation of remission periods between acute attacks of ulcerative colitis 1
• While not FDA-approved for rheumatoid arthritis, it is widely used as a disease-modifying antirheumatic drug (DMARD) 3, 4

Pharmacokinetics

• Following oral administration, less than 15% of sulfasalazine is absorbed as the parent drug 1
• Detectable serum concentrations appear within 90 minutes of ingestion 1
• Maximum concentrations occur between 3-12 hours post-ingestion (mean peak at 6 hours) 1
• The drug is highly bound to albumin (>99.3%) 1
• The observed plasma half-life for intravenous sulfasalazine is 7.6 ± 3.4 hours 1
• Metabolism of sulfapyridine is dependent on acetylator phenotype (fast vs. slow acetylators) 1, 2

Dosing

• For ulcerative colitis, typical dosing ranges from 1.5 to 4.0 g daily 5, 2
• Maintenance doses of 2-3 g/day are most likely to sustain remissions while avoiding toxicity 2
• Patients often need to start at lower doses with gradual escalation as tolerated due to side effects 5

Efficacy

• Effective for inducing and maintaining remission in ulcerative colitis 5
• Comparable efficacy to other 5-ASA preparations for ulcerative colitis, though with more side effects 5
• Limited efficacy in peripheral arthritis associated with inflammatory bowel disease 5
• Can be effective in large-joint arthropathy 5
• Not effective for axial spondyloarthritis 5
• Effective as a DMARD in rheumatoid arthritis with efficacy similar to hydroxychloroquine or gold 3, 4

Adverse Effects

• Gastrointestinal effects: nausea, vomiting, diarrhea, abdominal pain, dyspepsia (occurring in up to 35% of patients) 5, 6
• Headache and dizziness 3, 6
• Skin reactions: rash, urticaria 3, 6
• Hematologic toxicity: leukopenia, thrombocytopenia, anemia 5
• Hepatotoxicity: elevated liver enzymes, rare cases of hepatitis 5
• Allergic reactions 7, 6
• Side effects are more common in slow acetylators due to higher levels of free sulfapyridine 2
• Dyspeptic symptoms typically occur within days of starting treatment, while extraintestinal manifestations (like rash) appear after 1-3 weeks 6

Monitoring Requirements

• Complete blood count monitoring is recommended due to potential hematologic toxicity 5
• Liver function tests should be monitored 5
• Determination of acetylator phenotype and total sulfapyridine concentration can guide effective dosage and help avoid side effects 2

Special Considerations

• Sulfasalazine interferes with folic acid metabolism, requiring folate supplementation 5
• May be more difficult to incorporate into clinical practice due to adverse effects and need for laboratory monitoring 5
• Enteric-coated formulations (EN Sulfasalazine) may reduce dyspeptic side effects 6
• Unlike some other DMARDs, sulfasalazine may be suitable for women who are or may become pregnant 4
• Patients with concomitant arthritic symptoms may benefit from its use in ulcerative colitis 5
• In patients with inflammatory bowel disease-associated peripheral spondyloarthritis, sulfasalazine can be considered for mild disease 5

Comparison to Other 5-ASA Medications

• Mesalamine and diazo-bonded 5-ASA medications (balsalazide, olsalazine) are generally better tolerated than sulfasalazine 5
• Mesalamine and balsalazide have similar efficacy to sulfasalazine but with fewer side effects 5
• Systemic exposure to 5-ASA is similar across all oral mesalamine preparations and diazo-bonded 5-ASAs 5