NSAID Gastrointestinal Adverse Effects

1. See Also
   1. NSAID
   2. NSAID Alternatives
2. Risk Factors: NSAID related GI adverse effects
   1. Age over 60 years (decreased GI protection)
   2. Peptic Ulcer Disease history
   3. Concurrent Corticosteroid use
   4. Concurrent oral Anticoagulation (Coumadin, Aspirin)
   5. High dose NSAID
3. Risk Factors: Relative Risks of GI adverse effects
   1. Lowest Risk: COX2 Inhibitors (Selective)
      1. Celecoxib (Celebrex)
      2. Rofecoxib (Vioxx)
   2. Low Risk (Non-Selective NSAIDs)
      1. Ibuprofen (Relative Risk 1.0 to 2.7)
      2. Fenoprofen or Nalfon (Relative Risk 1.6)
      3. Aspirin (Relative Risk 1.6)
      4. Diclofenac or Voltaren (Relative Risk 1.8 to 4.0)
      5. Sulindac or Clinoril (Relative Risk 2.1)
      6. Nabumetone or Relafen
      7. Etodolac or Lodine
      8. Salsalate
   3. Medium Risk
      1. Diflunisal or Dolobid (Relative Risk 2.2)
      2. Naproxen or Naprosyn (Relative Risk 2.2 to 5.2)
      3. Indomethacin or Indocin (Relative Risk 2.4 to 5.3)
      4. Tolmetin or Tolectin (Relative Risk 3.0)
      5. Meloxicam or Mobic (Relative Risk 4.0)
   4. High Risk
      1. Piroxicam or Feldene (Relative Risk 3.8 to 9.3)
      2. Ketoprofen or Orudis (Relative Risk 4.2 to 5.7)
      3. Azapropazone (Relative Risk 9.2)
      4. Flurbiprofen or Ansaid
      5. Ketorolac or Toradol (Relative Risk 14.0)
4. Adverse Effects: Gastroduodenal Ulcer Incidence by endoscopy (12 weeks)
   1. Naprosyn: 35%
   2. Ibuprofen: 23-29% (2 different trials)
   3. Diclofenac: 10%
   4. Rofecoxib: 5-8% (25-50 mg)
   5. Celecoxib: 7%
   6. Placebo: 4-7% (2 different trials)
   7. References
      1. (1999) Med Lett Drugs Ther 41(1045): 11-14
      2. Laine (1999) Gastroenterology 116:A229
5. Management: Prophylaxis
   1. General
      1. Always use NSAID with food or milk
      2. COX2 Inhibitors have no advantage over standard NSAID
      3. Consider screening for Helicobacter Pylori before use
   2. Indications for prophylaxis (avoid NSAIDs if possible)
      1. Age over 75 years
      2. Concurrent Warfarin therapy
      3. History of Peptic Ulcer Disease
      4. History of Gastrointestinal Bleeding
      5. History of Coronary Artery Disease
   3. Misoprostol (Cytotec)
      1. Dose: 100-200 ug tid to qid
      2. Replaces prostaglandins at Stomach lining
      3. Allows use of NSAIDS in Peptic Ulcer Disease
      4. Causes significant dose limiting Diarrhea
   4. Sucralfate
      1. Ineffective at preventing NSAID related Peptic Ulcers
   5. H2 Receptor Antagonists (e.g. Zantac, Tagamet)
      1. Not recommended (may mask GI symptoms)
      2. Prevents Duodenal Ulcer, not Gastric Ulcer
      3. Consider high dose H2 Antagonist
   6. Omeprazole
      1. Heals, but may not protect from formation
6. References
   1. Henry (1996) BMJ 312:1563-6
   2. (1999) Med Lett Drugs Ther 41(1045): 11-14
   3. Masso (2010) Arthritis Rheum 62(6): 1592-1601