Drug reference

Sulfasalazine

Aminosalicylate · Anti-inflammatory, Immunomodulator, Antirheumatic

Also known as Azulfidine, Salazopyrin, Sulfasalazine EC

AminosalicylateAnti-inflammatory, Immunomodulator, Antirheumatic

CDSCO approvedSchedule H

EXCRETION

—

not curated

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

Category B; use with caution. Adequate folic acid supplementation (at least 2 mg/day) is essential due to potential for folate antagonism. Weigh benefits vs. risks.

FDA category + note

Top interactionssee all 12 →

Aceclofenac + ParacetamolContraindicatedTextbookG&G 14e · p1112
AceclofenacContraindicatedTextbookG&G 14e · p1112
AspirinContraindicatedTextbookG&G 14e · p1112
CapsaicinContraindicatedTextbookG&G 14e · p1112

Mechanism

Sulfasalazine is a prodrug cleaved by colonic bacteria into sulfapyridine and 5-aminosalicylic acid (5-ASA). 5-ASA acts locally in the inflamed colon as an anti-inflammatory by inhibiting prostaglandin and leukotriene synthesis, modulating immune cell function, and scavenging free radicals. Sulfapyridine contributes to systemic anti-inflammatory effects and is responsible for many adverse effects.

Indications

Ulcerative colitis (induction and maintenance)Rheumatoid arthritis (adult and polyarticular juvenile)Crohn's disease (mild-to-moderate, off-label)Psoriatic arthritis (off-label)Rheumatoid arthritisInflammatory bowel diseasemild or moderately active ulcerative colitispreventing relapses in ulcerative colitissevere ulcerative colitis (as an adjunct to systemic glucocorticoids)ulcerative colitis

Dosing

Adult: Ulcerative Colitis: Initial 500 mg - 1 g orally 3-4 times daily, increasing gradually to 2-4 g/day in divided doses. Maintenance 2 g/day in divided doses. Rheumatoid Arthritis: Initial 500 mg orally once daily for 1 week, then 500 mg twice daily for 1 week, increasing gradually to 1 g twice daily.
Pediatric: Ulcerative Colitis (>2 years): Initial 40-60 mg/kg/day orally in 3-6 divided doses. Maintenance 30 mg/kg/day in 4 divided doses. Max 2 g/day. Juvenile Rheumatoid Arthritis (>6 years, >25 kg): Initial 10 mg/kg/day orally, increasing weekly by 10 mg/kg/day. Maintenance 30-50 mg/kg/day in 2 divided doses.
Renal adjustment: Use with caution. If eGFR <30 mL/min/1.73m2, reduce dose or extend interval. Contraindicated in severe renal impairment. Ensure hydration and monitor renal function. Avoid if CrCl <10 mL/min.

Pharmacokinetics

Onset

8-12 hours for anti-inflammatory effects in gut (longer for rheumatic diseases: weeks to months)

Peak effect

Sulfasalazine: 1.5-6 hours; Sulfapyridine: 6-24 hours; 5-ASA: 10-30 hours (with enteric coating)

Protein binding

Sulfasalazine: >99%; Sulfapyridine: ~50%; 5-ASA: ~43%

Metabolism

Sulfapyridine undergoes extensive hepatic metabolism, including acetylation, hydroxylation, and conjugation with glucuronic acid. Mesalamine is acetylated in the intestinal mucosal wall and liver.

Excretion

Absorbed sulfasalazine is excreted unmetabolized in the bile; ~10% is excreted unchanged in the urine. Sulfapyridine is absorbed rapidly from the colon and undergoes extensive hepatic metabolism, then excreted in the urine. Mesalamine is acetylated in the intestinal mucosal wall and liver, then excreted in the urine, with most of the unabsorbed drug excreted in the stool.

Contraindications

Hypersensitivity to sulfasalazine, sulfonamides, or salicylates
Porphyria
Intestinal or urinary obstruction
Children under 2 years of age
Severe renal or hepatic impairment
G6PD deficiency

Side effects

Common

Nauseavomitingdiarrheaabdominal discomfortanorexiaheadacherashfeverreversible oligospermiayellow-orange discoloration of urine/skin/contact lensesUrine and skin discolorationsIncidence of side effects increased in slow acetylatorsfatigue (dose-related, minimized by taking with meals or decreasing dose)

Serious

Blood dyscrasias (agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, thrombocytopenia)
Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS syndrome)
Hepatotoxicity (including fulminant hepatic failure)
Interstitial nephritis
Crystalluria
Hypersensitivity reactions (e.g., serum sickness-like reactions)
Pulmonary fibrosis
Peripheral neuropathy
Lupus-like syndrome
Pancreatitis
Neurotoxicity
Hemolytic anemia (increased risk and severity in G-6PD deficient individuals)
Susceptibility to hemolytic anemia (with G6PD deficiency)
rash (allergic reaction)
fever (allergic reaction)
Stevens-Johnson syndrome (allergic reaction)
hepatitis (allergic reaction)
pneumonitis (allergic reaction)
hemolytic anemia (allergic reaction)
bone marrow suppression (allergic reaction)
reversibly decreased number and motility of sperm
inhibited intestinal folate absorption

Pregnancy & lactation

Pregnancy

Category B; use with caution. Adequate folic acid supplementation (at least 2 mg/day) is essential due to potential for folate antagonism. Weigh benefits vs. risks.

Drug interactions

Aceclofenac + Paracetamol

Contraindicated

Textbook

Exacerbation of inflammatory bowel disease (IBD).