SULFASALAZINE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Sulfasalazine is a prodrug that is cleaved by bacterial azoreductases in the colon to release 5-aminosalicylic acid (5-ASA) and sulfapyridine. 5-ASA reduces inflammation by inhibiting cyclooxygenase and lipoxygenase pathways, decreasing prostaglandin and leukotriene synthesis; it also scavenges reactive oxygen species and inhibits NF-κB activation. Sulfapyridine exerts antibacterial effects.

What the body does with it

Metabolism	Sulfasalazine is azo-reduced by gut bacterial enzymes to 5-ASA and sulfapyridine. Sulfapyridine undergoes acetylation (NAT2) and glucuronidation; 5-ASA is N-acetylated (NAT1) and excreted renally.
Excretion	Renal: 30% sulfapyridine and metabolites, 5-10% unchanged sulfasalazine; Biliary/fecal: remainder via bile into feces, with 5-10% eliminated in feces as parent drug.
Half-life	Sulfasalazine: 5–10 h (metabolized to sulfapyridine, which has a half-life of 10–15 h; sulfapyridine elimination is genetically determined [slow acetylators: 14.8 h; fast acetylators: 10.4 h]).
Protein binding	Sulfasalazine: >99% bound to albumin; Sulfapyridine: ~70% bound to albumin.
Volume of Distribution	Sulfasalazine: 0.1–0.2 L/kg (limited to plasma and extracellular fluid); Sulfapyridine: 0.3 L/kg.
Bioavailability	Oral: 10–20% for parent sulfasalazine (due to bacterial cleavage in colon); sulfapyridine is 100% absorbed after cleavage.
Onset of Action	Oral: 3–5 days for initial response in ulcerative colitis; 6–12 weeks for full therapeutic effect in rheumatoid arthritis.
Duration of Action	Dosing interval 6–12 h; steady state achieved in ~2–3 days for sulfasalazine and 3–5 days for sulfapyridine.

Classification & Brands

Dosing & administration

Initial: 500 mg orally twice daily; maintenance: 1 g orally twice daily. Maximum daily dose: 3 g.

Dosage form	TABLET
Renal impairment	GFR 30-60 mL/min: use 50% of standard dose. GFR <30 mL/min: contraindicated due to accumulation of sulfapyridine.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: use 50% of standard dose. Child-Pugh C: contraindicated.
Pediatric use	Children ≥6 years: 30-50 mg/kg/day orally divided into 2 doses; maximum 2 g/day.
Geriatric use	Initiate at low doses (500 mg once daily) with gradual titration; monitor renal function and blood counts due to increased risk of adverse effects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

May reduce absorption of digoxin and folic acid Can cause oligospermia and orange-yellow discoloration of urine and skin.

Breastfeeding	M/P ratio approximately 0.5-0.6. Sulfasalazine and its metabolite sulfapyridine are excreted into breast milk in low concentrations. Risk of hemolytic anemia in G6PD-deficient infants. Avoid in premature or ill infants; otherwise, considered compatible with monitoring.
Teratogenic Risk	FDA Pregnancy Category B. First trimester: No increased risk of major congenital malformations based on large cohort studies. Second and third trimesters: Risk of neonatal hemolytic anemia, particularly in G6PD-deficient infants; kernicterus reported. Risk of folate deficiency; supplementation recommended.

Warnings & precautions

■ FDA Black Box Warning

Not applicable.

Side Effect Profile

Common Effects	rheumatoid arthritis
Serious Effects

Absolute Contraindications

["Hypersensitivity to sulfasalazine, its metabolites, or any component","Hypersensitivity to sulfonamides or salicylates","Porphyria","Urinary tract obstruction","Intestinal obstruction","Severe liver disease","Severe renal impairment"]

Clinical Precautions

Precautions

["Blood dyscrasias: agranulocytosis, aplastic anemia; monitor CBC regularly.","Hepatotoxicity: monitor liver function tests.","Renal toxicity: maintain adequate hydration.","Hypersensitivity reactions: rash, Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS).","Oligospermia and infertility: reversible upon discontinuation.","Photosensitivity: avoid excessive sun exposure.","Folate deficiency: may cause folate malabsorption; consider folic acid supplementation."]

Clinical Tips & Counseling

Drug interactions

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