Generic Name

Azulfidine

Mechanism

• Prodrug hydrolysis – In the colon, gut flora enzymatically cleave Azulfidine to release sulfapyridine (antimicrobial) and 5‑aminosalicylic acid (5‑ASA) (anti‑inflammatory).
• Immunomodulation – 5‑ASA inhibits prostaglandin and leukotriene synthesis, scavenges reactive oxygen species, and down‑regulates NF‑κB activation, thereby attenuating cytokine release from activated macrophages and T lymphocytes.
• Microbial effects – Sulfapyridine suppresses bacterial proliferation, reducing luminal antigenic load.

Pharmacokinetics

• Absorption – Variable; ~50 % absorbed in the small intestine, 55–90 % of the dose remains unmetabolized to the colon.
• Distribution – Extensive protein binding (~90 % in plasma).
• Metabolism – Hepatic esterases and conjugation; minimal CYP involvement.
• Elimination – Renal excretion of sulfapyridine (renal clearance ~1.5 L/h) and 5‑ASA; half‑life of the drug: 6–11 h (sulfapyridine), 11–18 h (5‑ASA).
• Special populations – Dose reduction or avoidance in severe renal or hepatic impairment; observe in pregnancy (Category C).

Indications

• Rheumatoid arthritis – as monotherapy or combination with NSAIDs, steroids, or DMARDs.
• Inflammatory bowel disease – ulcerative colitis (ulcerative colitis) and Crohn’s disease (short courses).
• Other – Behçet’s disease (off‑label) and ankylosing spondylitis (off‑label).

Contraindications

• Hypersensitivity to sulfonamides, sulfapyridine, or 5‑ASA.
• Pregnancy – Avoid because of fetal sulfa exposure.
• Severe renal/hepatic impairment – Not recommended.
• S. penicillin–associated immune disorders – careful cross‑reactivity assessment.
• Drug–drug interactions – Avoid concomitant use with azathioprine or cyclosporine (overlap in hematologic toxicity).
• Lupus erythematosus, especially drug‑induced lupus, warrants caution.

Dosing

• Start low, titrate up over 2–4 weeks to avoid GI upset and hemolysis.
• Take with meals or milk to reduce gastritis.
• Avoid alcohol consumption.

Adverse Effects

Common (≥1 %):
• Nausea, vomiting, diarrhea, abdominal discomfort.
• Headache, dizziness.
• Rash, mild pruritus.

Serious (≤1 %):
• Hematologic: agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia.
• Hepatotoxicity: elevated transaminases, hepatitis.
• Hypersensitivity: rash, eosinophilia, serum sickness, hemolytic anemia.
• Renal: interstitial nephritis, impaired creatinine clearance.
• CNS: seizures (rare).

> Note: Hematologic and hepatic toxicity appear most often within the first 12 weeks.

Monitoring

• Baseline & periodic CBC (before day 14, then monthly for 6 months).
• LFTs (baseline, week 4, then every 3–6 months).
• Renal function (serum creatinine, BUN).
• Pregnancy test in women of childbearing age.
• Fasting lipids and weight monitoring given potential weight gain.
• Adherence check (due to titration schedule).

Clinical Pearls

• “Sulfa‑sensitivity first.” Screen patients for sulfonamide allergy before initiating Azulfidine; a positive test warrants alternative DMARDs.
• “Slow titration equals fewer crashes.” Rapid dose escalation magnifies GI and hematologic toxicity; gradual increase improves tolerability.
• “Keep eyes on the CBC.” Agranulocytosis can develop insidiously; a drop in neutrophils below 1 × 10⁹/L often predicts impending severe infection.
• “Pregnancy‑friendly? No.” Women planning conception should discontinue Azulfidine at least 24 h before conception; a washout period of 3 days is generally sufficient due to short half‑life.
• “Drug‑interaction watchful.” Co‑administration with azathioprine or cyclosporine can potentiate bone marrow suppression; consider dose adjustments and closer hematologic surveillance.
• “Use the 1‑g formulation wisely.” The 1‑g tablet can reduce pill burdens; but patients with dysphagia may require splitting 500‑mg tablets.

> Bottom line: Azulfidine serves as a versatile, albeit time‑consuming, anti‑inflammatory agent for RA and IBD. Mastery of its pharmacokinetics, monitoring, and early recognition of toxicity maximizes patient benefit while minimizing harm.