Generic Name

Sulfasalazine

Mechanism

• Dual‑action drug:
• 5‑ASA: acts locally in the colon to inhibit cyclooxygenase (COX) and lipoxygenase (LOX), scavenges free radicals, and modulates prostaglandin & leukotriene synthesis.
• Sulfapyridine: exhibits systemic immunomodulatory effects, including inhibition of folate metabolism, suppression of T‑cell proliferation, and antiproliferative activity on intestinal epithelial cells.
• Metabolic activation: colonic bacteria cleave the amide bond, liberating 5‑ASA where it exerts its therapeutic effect while the sulfapyridine is absorbed systemically.
• Anti‑oxidant and anti‑inflammatory properties reduce mucosal edema and ulceration in ulcerative colitis and colonic Crohn's disease.

Pharmacokinetics

• Route: oral; bioavailability ~10 % of the dose absorbed in the small intestine.
• Absorption: primarily in the upper GI tract; hepatic metabolism minimal; the remainder reaches the colon intact.
• Metabolism: split at intestinal dihydropyridase → 5‑ASA (inactive in the small bowel) and sulfapyridine.
• Sulfapyridine → N‑acetylsulfapyridine (main metabolite) and N‑hydroxysulfapyridine.
• Distribution: protein‑binding ~97 %; large volume of distribution.
• Elimination:
• Sulfapyridine: renal excretion (70 %) after hepatic N‑acetylation; half‑life 12–20 h.
• 5‑ASA: fecal excretion; half‑life 2–3 h.
• Special considerations: renally impaired patients may need dose adjustment; hepatic dysfunction may prolong sulfapyridine exposure.

Indications

Contraindications

• Contraindicated
• Known hypersensitivity to sulfonamides, sulfapyridine, or 5‑ASA.
• Severe hepatic impairment (AST/ALT >3× ULN).
• Severe renal impairment (CrCl 3× ULN warrants discontinuation.
• Serum sickness–like reactions and Stevens‑Johnson syndrome: rare but severe.
• Pregnancy: Category C; avoid if possible; use contraception if non‑critical.
• Galactorrhea and hyperprolactinemia: risk of paradoxical breast stimulation.
• Gastro‑intestinal upset: nausea, constipation, loss of appetite.

Dosing

• Initial titration: 500 mg orally every 12 h (1 g/day) for 2 weeks, then increase 1 g/day every 1–2 weeks until the maximum dose.
• Maintenance:
• IBD: 1.5–2.5 g/day (split into 2–4 doses).
• RA: 1.5–3 g/day (split).
• Administration advice
• Take with meals to reduce GI upset.
• Use a splitting device to divide tablets; avoid crushing full tablets.
• Do not combine with rifampin or classic carbamazepine (enzyme induction) without dose adjustment.
• Special populations
• *Pregnancy*: use only if clearly needed; consult obstetrician.
• *Elderly*: monitor renal/hepatic function; start low and titrate.
• *Hepatic impairment*: reduce or discontinue if LFTs rise >3× ULN.

Adverse Effects

Common (≥10 % incidence)
• Nausea, vomiting
• Abdominal pain, cramping
• Rash (maculopapular, urticaria)
• Headache
• Dysuria, hematuria
• Arthralgia, myalgia
• Diarrhea/constipation

Serious (≤1 % incidence)
• Leukopenia, neutropenia, agranulocytosis
• Severe hepatotoxicity (ALT/AST >5× ULN)
• Serum sickness–like reaction (fever, rash, swelling)
• Stevens‑Johnson syndrome / Toxic epidermal necrolysis
• Pulmonary infiltrates / interstitial lung disease
• Hemolytic anemia (in G‑6‑PD deficiency)
• Drug‑induced lupus erythematosus (rare)

Monitoring

Clinical Pearls

• Bioavailability is low; give with food to improve tolerance but avoid high‑fat meals that delay absorption.
• Splitting tablets is essential—whole tablets have poor colonic release, leading to systemic sulfa toxicity.
• Colonic bacteria are required for activation; patients on broad‑spectrum antibiotics may experience reduced efficacy temporarily.
• Sulfa allergy presents more commonly with rash, fever, or eosinophilia; a skin patch test may rule out mild sensitivity if treatment is essential.
• Test for G‑6‑PD deficiency before initiating therapy in patients of African, Mediterranean, or Asian descent to prevent hemolytic anemia.
• Thickened sputum or cough in patients on the drug may signal rare interstitial lung disease—immediate discontinuation is advised.
• Pregnancy category C: if essential for colitis control, cross‑reference to low‑dose 5‑ASA preparations (mesalamine) which may be safer.
• Drug interactions: avoid concomitant use of classic carbamazepine or rifampin; they increase sulfapyridine clearance, necessitating dose adjustment.
• Monitoring for intolerance: if chronic rash or GI upset occurs, consider switching to mesalamine or bismuth‑based preparations with lesser sulfa burden.
• Short‑term therapy: For Crohn’s disease flare, a high‑dose short course (1–1.5 g/day for 2–4 weeks) may suffice, followed by weaning.

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• *This drug card consolidates key pharmacology, dosing, and safety information for Sulfasalazine to aid rapid reference for clinicians and learners.*