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Sulfasalazine

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Sulfasalazine, Azulfidine

  • See Also
  1. 5-Aminosalicylic Acid Derivative
  2. Mesalamine
  3. Balsalazide
  4. Olsalazine
  • Indications
  1. Inflammatory Bowel Disease (e.g. Ulcerative Colitis)
  2. Rheumatoid Arthritis (especially seronegative)
    1. Second-line agent in combination with Methotrexate and Hydroxychloroquine
  3. Psoriatic Arthritis
  4. Arthritis in Reiter's Syndrome
  • Contraindications
  1. Significant renal dysfunction
  2. Significant hepatic dysfunction
  3. Bowel Obstruction
  4. Porphyria
  5. G6PD Deficiency
    1. Risk of Hemolysis
    2. Screen for G6PD Deficiency before dosing
  6. Sulfa Allergy
    1. Consider Mesalamine (Asacol, Pentasa) as alternative
    2. Consider slowly tapering to dose if unclear allergy
      1. Start: 250 grams per day
      2. Increase: 250 grams per week
  • Mechanism
  1. Derivative of 5-Aminosalicylic Acid (synthetic salicylic acid)
  2. Prodrug, metabolized into sulfapyridine and Mesalamine by colonic Bacteria
    1. Ideal location for activation in Inflammatory Bowel Disease (esp. Ulcerative Colitis)
  3. Active at connective tissues containing elastin (including those affected by Rheumatoid Arthritis)
    1. Metabolites have antiinflammatory activity via inhibition of cyclooxygenase and Prostaglandin production
  • Medications
  1. Sulfasalazine (Azulfidine)
    1. Available as 500 mg oral tablets
    2. Total 4 grams is equivalent to 1.6 grams 5-ASA
  2. Enteric-coated Sulfasalazine (Azulfidine EN Tabs)
    1. Available as 500 mg delayed release tablets
    2. Total 4 grams is equivalent to 1.6 grams 5-ASA
    3. Better tolerated than standard Sulfasalazine
  1. Start 500 mg orally once to twice daily
  2. May titrate to 500 mg three times daily OR 1000 mg twice daily
  1. General
    1. Increase slowly to lowest effective dose
    2. Co-administer Folic Acid 1 mg/day
    3. Starting Protocol (example in adults)
      1. Start: 500 mg per day
      2. Increase: 500 mg per week up to 2 grams per day
      3. Increase: 3 grams per day after 3 months
      4. Maximum: 4 grams per day (2 grams twice daily) after 6 months
  2. Active Disease (Induction)
    1. Take 500 to 1000 mg orally four times daily (max: 4 to 6 g/day)
  3. Maintenance
    1. Take 500 orally four times daily (max: 2 to 4 g/day)
  1. Avoid in age <2 years
  2. Supplement Folic Acid
  3. Active Disease (Induction) for age 6 years and older
    1. Give 40 to 60 mg/kg/day orally divided 3 to 6 times daily (max: 75 mg/kg/day)
  4. Maintenance for age 6 years and older
    1. Give 30 mg/kg/day orally divided 4 times daily with food
  • Adverse Effects
  1. General
    1. Take Folic Acid 1-2 mg/day
  2. Nausea and other Gastrointestinal Intolerance (30%)
    1. Decreased appetite
    2. Dyspepsia
    3. Nausea or Vomiting
    4. Consider enteric coated Azulfidine EN-tablets (better tolerated)
  3. Neurologic adverse effects
    1. Headache (20%)
    2. Dizziness or Lightheaded (<20%)
  4. Hematologic adverse effects (marrow suppression)
    1. Folate-inhibition Anemia
    2. Hemolytic Anemia
    3. Granulocytopenia and Leukopenia
    4. Thrombocytopenia
  5. Pulmonary
    1. Fibrosing Alveolitis
  6. Skin rash associated with Sulfa Allergy
    1. Requires discontinuing medication immediately
  7. Sexual Function
    1. Oligospermia (Infertility risk)
  8. Renal adverse effects
    1. Urine Discoloration (orange)
      1. May also discolor other body fluids (e.g. tears and Contact Lenses)
    2. Micro-Crystalluria
      1. Risk of Interstitial Nephritis
      2. Avoid Dehydration
      3. Avoid high doses
  • Drug Interactions
  1. Decreases other drug levels
    1. Folic Acid
    2. Digoxin
    3. Cyclosporine
    4. Serum Iron
  • Safety
  1. Pregnancy Category B
    1. However, Folate supplementation is critical
  2. Unknown safety in Lactation
    1. Case reports of nursing infants with Diarrhea and bloody stools
  3. Monitoring
    1. Complete Blood Count (CBC) every 2 to 4 weeks for 3 months, then every 3 to 6 months
    2. Aspartate Aminotransferase (AST, SGOT) at 2 months
    3. Serum Creatinine
  • Resources
  1. Sulfasalazine Tablets (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ddbe69f3-bd55-45f3-a64f-f60226c744c4
  • References
  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  2. (2022) Treatment of Mild to Moderate Ulcerative Colitis, Presc Lett, #350406
  3. (2023) Drugs for Inflammatory Bowel Disease, Med Lett Drug Ther 65: 105-12
  4. Adams (2013) Am Fam Physician 87(10): 699-705 [PubMed]
  5. Adams (2022) Am Fam Physician 105(4): 406-11 [PubMed]
  6. Kornbluth (2010) Am J Gastroenterol 105(3): 501-23 [PubMed]
  7. Matteson (2000) Mayo Clin Proc 75:669-74 [PubMed]
  8. Pincus (1999) Clin Rheumatol 17(6 Suppl 18):S2-S124 [PubMed]