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Ibuprofen: Pharmacology, Therapeutics and Side Effects pp 123–139Cite as

Gastro-Intestinal Toxicity

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Abstract

The gastro-intestinal toxicity of ibuprofen is considered in relation to dosage of the drug and clinical indications where the drug is applied, e.g. in prescription level dosage in rheumatic and musculo-skeletal pain and in OTC dosages in short-term usage for relief of acute pain and inflammation. Factors influencing the development of NSAID-associated upper gastro-intestinal (GI) ulceration and bleeding are considered. Evidence is considered for relative GI adverse reactions from ibuprofen in epidemiological studies and clinical trials in comparison with other NSAIDs, paracetamol and the newer coxibs. The GI adverse reactions from ibuprofen in children are compared with those from paracetamol.

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References

  • Aabakken L, Dybdahl JH, Larsen S, Mowinckel P, Osnes M, Quiding H (1989a) A double-blind comparison of gastrointestinal effects of ibuprofen standard and ibuprofen sustained release assessed by means of endoscopy and 51Cr-labelled erythrocytes. Scand J Gastroenterol 24:307–313

    Google Scholar 

  • Aabakken L, Dybdahl JH, Eidsaunet W, Haaland A, Larsen S, Osnes M (1989b) Optimal assessment of gastrointestinal side effects induced by non-steroidal anti-inflammatory drugs. Endoscopic lesions, faecal blood loss, and symptoms not necessarily correlated, as observed after naproxen and oxindanac in healthy volunteers. Scand J Gastroenterol 24:1007–1013

    Article  PubMed  CAS  Google Scholar 

  • Arroyo M, Lanas A (2006) NSAID-induced gastrointestinal damage. Minerva Gastroenterol Dietol 52:249–259

    PubMed  CAS  Google Scholar 

  • Ashraf E, Ford L, Geetha R, Cooper S (1999) Safety profile of ibuprofen suspension in young children. Inflammopharmacology 7:219–225

    Article  PubMed  CAS  Google Scholar 

  • Ashraf E, Cooper S, Kellstein D, Jayawardena S (2001) Safety profile of non-prescription ibuprofen in the elderly osteoarthritic patient: a meta-analysis. Inflammopharmacology 9:35–41

    Article  CAS  Google Scholar 

  • Bergmann JF, Chassany O, Geneve J, Abiteboul M, Caulin C, Segrestaa JM (1992) Endoscopic evaluation of the effect of ketoprofen, ibuprofen and aspirin on the gastroduodenal mucosa. Eur J Clin Pharmacol 42:685–688

    Article  PubMed  CAS  Google Scholar 

  • Beyth RJ, Shorr RI (1999) Epidemiology of adverse drug reactions in the elderly by drug class. Drugs Aging 14:231–239

    Article  PubMed  CAS  Google Scholar 

  • Biskupiak JE, Brixner DI, Howard K, Oderda GM (2006) Gastrointestinal complications of over-the-counter nonsteroidal anti-inflammatory drugs. J Pain Palliat Care Pharmacother 20:7–14

    Article  PubMed  Google Scholar 

  • Bjarnason I, Rainsford KD (2001) COX-2 inhibitors and the gastrointestinal tract. Gut 48:451

    Article  PubMed  CAS  Google Scholar 

  • Boureau F, Schneid H, Zeghari N, Wall R, Bourgeois P (2004) The IPSO study: ibuprofen, paracetamol study in osteoarthritis. A randomised comparative clinical study comparing the efficacy and safety of ibuprofen and paracetamol analgesic treatment of osteoarthritis of the knee or hip. Ann Rheum Dis 63:1028–1034

    Article  PubMed  CAS  Google Scholar 

  • Bowen B, Yuan Y, James C, Rashid F, Hunt RH (2005) Time course and pattern of blood loss with ibuprofen treatment in healthy subjects. Clin Gastroenterol Hepatol 3:1075–1082

    Article  PubMed  CAS  Google Scholar 

  • Buchanan WW (1990) Implications of NSAID therapy in elderly patients. J Rheumatol 17:29–32

    Google Scholar 

  • Buckler JW, Hall JE, Rees JA, Sheldrake FE, Miller AC (1975) The tolerance and acceptability of ibuprofen (‘Brufen’) in the elderly patient. Curr Med Res Opin 3:558

    Article  Google Scholar 

  • De Medicinis R, LeBel E, Rioux A et al (1988) Biliary excretion of radiochromium. Am J Med 85:276

    Article  Google Scholar 

  • Doyle G, Furey S, Berlin R, Cooper S, Jayawardena S, Ashraf E, Baird L (1999) Gastrointestinal safety and tolerance of ibuprofen at maximum over-the-counter dose. Aliment Pharmacol Ther 13:897–906

    Article  PubMed  CAS  Google Scholar 

  • Friedman H, Seckman C, Stubbs C, Oster H, Royer G (1990a) Multiple-dose safety study of ibuprofen/codeine and aspirin/codeine combinations. J Clin Pharmacol 30:65–69

    PubMed  CAS  Google Scholar 

  • Friedman H, Seckman C, Lanza F, Royer G, Perry K, Francom S (1990b) Clinical pharmacology of predisintegrated ibuprofen 800mg tablets: an endoscopic and pharmacokinetic study. J Clin Pharmacol 30:57–63

    PubMed  CAS  Google Scholar 

  • Garcia-Rodriguez LA, Hernandez-Diaz S (2001) The risk of upper gastrointestinal complications associated with nonsteroidal anti-inflammatory drugs, glucocorticoids, acetaminophen, and combinations of these agents. Arthritis Res 3:98–101

    Google Scholar 

  • Griffin MR, Ray WA, Schaffner W (1988) Nonsteroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons. Ann Intern Med 109:359–363

    PubMed  CAS  Google Scholar 

  • Henry D, McGettigan P (2003) Epidemiology overview of gastrointestinal and renal toxicity of NSAIDs. Int J Clin Pract Suppl (135):43–49

    Google Scholar 

  • Henry DA, Dobson A, Turner C (1993) Variability in the risk of major gastrointestinal complications from non-aspirin nonsteroidal anti-inflammatory drugs. Gastroenterology 105:1078–1088

    PubMed  CAS  Google Scholar 

  • Henry D, Lim LL-Y, Garcia Rodriguez LA, Perez Gutthann S, Carson JL, Griffin M, Savage R, Logan R, Moride Y, Hawkey C et al (1996) Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. Br Med J 312:1563–1566

    Article  CAS  Google Scholar 

  • Henry DA, Drew A, Beuzeville S (1998) Adverse drug reactions in the gastrointestinal system attributed to ibuprofen. In: Rainsford KD, Powanda MC (eds) Safety and efficacy of non-prescription (OTC) analgesics and NSAIDs. Kluwer Academic, Dodrecht, pp 19–45

    Chapter  Google Scholar 

  • Hippisley-Cox J, Coupland C, Logan R (2005) Risk of adverse gastrointestinal outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. Br Med J 331:1310–1316

    Article  CAS  Google Scholar 

  • Hunt RH, Bowen B, Mortensen ER, Simon TJ, James C, Cagliola A, Quan H, Bolognese JA (2000) A randomized trial measuring faecal blood loss after treatment with rofecoxib, ibuprofen, or placebo in healthy subjects. Am J Med 109:201–206

    Article  PubMed  CAS  Google Scholar 

  • Jüni P, Rutjes AWS, Dieppe PA (2002) Are selective COX-2 inhibitors superior to traditional nonsteroidal anti-inflammatory drugs. Br Med J 324:1287–1288

    Article  Google Scholar 

  • Kaufman DW, Kelly JP, Sheehan JE, Laszlo A, Wiholm BE, Alfredsson L, Koft RS, Shapiro S (1993) Nonsteroidal anti-inflammatory drug use in relation to major gastrointestinal bleeding. Clin Pharmacol Ther 53:485–494

    Article  PubMed  CAS  Google Scholar 

  • Kean WF, Kean IRL, Rainsford KD (2008) Gastrointestinal complications of anti-rheumatic drugs. In: Font J, Ramos-Casals M, Rodes J (eds) Handbook of systemic autoimmune diseases, vol 8. Digestive involvement in systemic autoimmune diseases. Elsevier, Amsterdam, pp 243–275

    Google Scholar 

  • Kellstein DE, Waksman JA, Furey SA, Binstok G, Cooper SA (1999) The safety profile of nonprescription ibuprofen in multiple-dose use: a meta-analysis. J Clin Pharmacol 39:520–532

    PubMed  CAS  Google Scholar 

  • Laine L (2001) Approaches to nonsteroidal anti-inflammatory drug use in the high-risk patient. Gastroenterology 120:594–606

    Article  PubMed  CAS  Google Scholar 

  • Laine L, Smith R, Min K, Chen C, Dubois RW (2006) Systematic review: the lower gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 24:751–767

    Article  PubMed  CAS  Google Scholar 

  • Lanas A (2010) A review of the gastrointestinal safety data–a gastroenterologist’s perspective. Rheumatology 49(Suppl 2):ii3–ii10

    Article  PubMed  CAS  Google Scholar 

  • Lanas A, Garcia-Rodriguez LA, Arroyo MT, Gomollon F, Feu F, Gonzalez-Perez A, Zapata E, Bastida G, Rodrigo L, Santolaria S, Güell M, de Argila CM, Quintero E, Borda F, Pique JM (2006) Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations. Gut 55:1731–1738

    Article  PubMed  CAS  Google Scholar 

  • Langman MJS, Weil J, Wainwright P, Lawson DH, Rawlins MD, Logan RFA, Murphy M, Vessey MP, Colin-Jones DG (1994) Risk of bleeding peptic ulcers associated with individual non-steroidal anti-inflammatory drugs. Lancet 343:1075–1078

    Article  PubMed  CAS  Google Scholar 

  • Lanza FL, Royer GL, Nelson RS, Chen TT, Seckman CE, Rack MF (1979) The effects of ibuprofen, indomethacin, aspirin, naproxen, and placebo on the gastric mucosa of normal volunteers. A gastroscopic and photographic study. Dig Dis Sci 24:823–828

    Article  PubMed  CAS  Google Scholar 

  • Lanza FL, Royer GL, Nelson RS, Chen TT, Seckman CE, Rack MF (1981) A comparative endoscopic evaluation of the damaging effects of nonsteroidal anti-inflammatory agents on the gastric and duodenal mucosa. Am J Gastroenterol 75:17–21

    PubMed  CAS  Google Scholar 

  • Lanza F, Rack MF, Lynn M, Wolf J, Sanda M (1987) An endoscopic comparison of the effects of etodolac, indomethacin, ibuprofen, naproxen, and placebo on the gastrointestinal mucosa. J Rheumatol 14:338–341

    PubMed  CAS  Google Scholar 

  • Lanza FL, Marathi UK, Anand BS, Lichtenberger LM (2008) Clinical trial: comparison of ibuprofen-phosphatidylcholine and ibuprofen on the gastrointestinal safety and analgesic efficacy in osteoarthritic patients. Aliment Pharmacol Ther 28:431–442

    Article  PubMed  CAS  Google Scholar 

  • Laporte J-R, Ibanez L, Vidal X, Vendrell L, Leone R (2004) Upper gastrointestinal bleeding associated with the use of NSAIDs. Newer versus older agents. Drug Saf 27:411–420

    Article  PubMed  CAS  Google Scholar 

  • Le Parc JM, Van Ganse E, Moore N, Wall R, Schneid H, Verrière F (2002) Comparative tolerability of paracetamol, aspirin and ibuprofen for short-term analgesia in patients with musculoskeletal conditions: results in 4291 patients. Clin Rheumatol 21:28–31

    Article  PubMed  Google Scholar 

  • Lesko SM, Mitchell AA (1995) An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial. JAMA 273:929–933

    Article  PubMed  CAS  Google Scholar 

  • Lewis JD, Kimmel SE, Localio AR, Metz DC, Farrar JT, Nessel L, Brensinger C, McGibney K, Strom BL (2005) Risk of serious upper gastrointestinal toxicity with over-the-counter nonaspirin nonsteroidal anti-inflammatory drugs. Gastroenterol 129:1865–1874

    Article  CAS  Google Scholar 

  • Lugardon S, Lapeyre-Mestre M, Montastruc JL (2004) Upper gastrointestinal adverse drug reactions and cyclo-oxygenase-2 inhibitors (celecoxib and rofecoxib): a case/non-case study from the French Pharmacovigilance Database. Eur J Clin Pharmacol 60:673–677

    Article  PubMed  CAS  Google Scholar 

  • MacDonald TM, Morant SV, Robinson GC, Shield MJ, McGilchrist MM, Murray FE, McDevitt DG (1997) Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: Cohort study. Br Med J 315:1333–1337

    Article  CAS  Google Scholar 

  • Mamdani M, Rochon PA, Juurlink DN, Kopp A, Anderson GM, Naglie G, Austin PC, Laupacis A (2002) Observational study of upper gastrointestinal haemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs. Br Med J 325:624–629

    Article  CAS  Google Scholar 

  • Moore N, Van Ganse E, Le Parc J-M et al (1999) The PAIN study (Paracetamol, Aspirin and Ibuprofen New Tolerability study): a large-scale randomised clinical trial comparing the tolerability of aspirin, ibuprofen, and paracetamol for short-term analgesia. Clin Drug Invest 28:89–98

    Article  Google Scholar 

  • Moore A, Derry S, Makinson GT, McQuay HJ (2005) Tolerability and adverse events in clinical trials of celecoxib in osteoarthritis and rheumatoid arthritis: systematic review and meta-analysis of information from company clinical trials reports. Arthritis Res Ther 7:R644–R665

    Article  PubMed  CAS  Google Scholar 

  • Müller P, Koch EMW, Simon B (1995) Schutzwirkung von Ranitidin bei Ibuprofen-Gastroduodenopathie. Arzneim Forsch/Drug Res 45:601–603

    Google Scholar 

  • Perez-Gutthann S, Garcia-Rodriguez LA, Duque-Oliart A, Varas-Lorenzo C (1999) Low-dose diclofenac, naproxen and ibuprofen cohort study. Pharmacotherapy 19:854–859

    Article  PubMed  CAS  Google Scholar 

  • Rainsford KD (1999c) Safety and efficacy of non-prescription (OTC) ibuprofen. In: Rainsford KD (ed) Ibuprofen: a critical bibliographic review. Taylor & Francis, London, pp 357–405

    Chapter  Google Scholar 

  • Rainsford KD (2004a) Side effects and toxicology of the salicylates. In: Rainsford KD (ed) Aspirin and related drugs. Taylor & Francis, London, pp 367–554

    Google Scholar 

  • Rainsford KD (ed) (2005b) Nimesulide. Actions and uses. Birkhäuser, Basel

    Google Scholar 

  • Rainsford KD (2009) Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacology 17:275–342

    Article  PubMed  CAS  Google Scholar 

  • Rainsford KD, Roberts SC, Brown S (1997) Ibuprofen and paracetamol: relative safety in non-prescription dosages. J Pharm Pharmacol 49:345–376

    Article  PubMed  CAS  Google Scholar 

  • Rainsford KD, Adesioye J, Dawson S (2001) Relative safety of NSAIDs and analgesics for non-prescription use or in equivalent doses. Inflammopharmacology 8:351–359

    Article  Google Scholar 

  • Rodriguez F, Llinas MT, Moreno C, Salazar FJ (2001) Role of cyclooxygenase-2-derived metabolites and NO in renal response to bradykinin. Hypertension 37:129–134

    Article  PubMed  CAS  Google Scholar 

  • Roth SH, Tindall EA, Jain AK, McMahon FG, April PA, Bockow BI, Cohen SB, Fleischmann RM (1993) A controlled study comparing the effects of nabumetone, ibuprofen, and ibuprofen plus misoprostol on the upper gastrointestinal tract mucosa. Arch Intern Med 153(22):2565–2571

    Google Scholar 

  • Schaffer D, Florin T, Eagle C, Marschner I, Singh G, Grobler M, Fenn C, Schou M, Curnow KM (2006) Risk of serious NSAID-related gastrointestinal events during long-term exposure: a systematic review. Med J Aust 185:501–506

    PubMed  Google Scholar 

  • Scheiman JM, Cryer B, Kimmey MB, Rothstein RI, Riff DS, Wolfe MM (2004) A randomized, controlled comparison of ibuprofen at the maximal over-the-counter dose compared with prescription-dose celecoxib on upper gastrointestinal mucosal injury. Clin Gastroenterol Hepatol 2:290–295

    Article  PubMed  CAS  Google Scholar 

  • Schneider HT, Nernberg B, Dietzel K, Brune K (1990) Biliary elimination on non-steroidal anti-inflammatory drugs in patients. Br J Clin Pharmacol 29:127–131

    Article  PubMed  CAS  Google Scholar 

  • Schoenfeld P (2001) An evidence-based approach to the gastrointestinal safety profile of COX-2 selective anti-inflammatories. Gastroenterol Clin North Am 30:1027–1044

    Article  PubMed  CAS  Google Scholar 

  • Seinelä L, Ahvenainen J (2000) Peptic ulcer in the very old patients. Gerontology 46:271–275

    Article  PubMed  Google Scholar 

  • Sikes DH, Agrawal NM, Zhao WW, Kent JD, Recker DP, Verburg KM (2002) Incidence of gastroduodenal ulcers associated with valdecoxib compared with that of ibuprofen and diclofenac in patients with osteoarthritis. Eur J Gastroenterol Hepatol 14:1101–1111

    Article  PubMed  CAS  Google Scholar 

  • Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM, Zhao WW, Kent JD, Lefkowith JB, Verburg KM, Geis GS (2000) Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis. JAMA 284:1247–1255

    Article  PubMed  CAS  Google Scholar 

  • Singh G (2000) Gastrointesstinal complications of prescription and over-the-counter nonsteroidal anti-inflammatory drugs: a view from the ARAMIS database. Arthritis, Rheumatism, and Aging Medical Information System. Am J Ther 7:115–121

    Article  PubMed  CAS  Google Scholar 

  • Singh G, Rosen Ramey D (1998) NSAID induced gastrointestinal complications: the ARAMIS perspective–1997. Arthritis, Rheumatism, and Aging Medical Information System. J Rheumatol Suppl 51:8–16

    PubMed  CAS  Google Scholar 

  • Singh G, Ramey DR, Morfeld D, Shi H, Hatoum HT, Fries JF (1996) Gastrointestinal tract complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis. A prospective observational cohort study. Arch Intern Med 156(14):1530–1536

    Article  PubMed  CAS  Google Scholar 

  • Teixeira AV, Abrunhosa R, Poças L (1977) Observations on the gastric mucosa of rheumatic patients before and after ibuprofen administration as studied by the pentagastrin test, endoscopy, and light and electron microscopy. Int J Med Res 5:243–252

    CAS  Google Scholar 

  • Thomsen RW, Riis A, Munk EM, Nørgaard M, Christensen S, Sørensen HT (2006) 30-day mortality after peptic ulcer perforation among users of newer selective COX-2 inhibitors and traditional NSAIDs: a population-based study. Am J Gastroenterol 101:2704–2710

    Article  PubMed  CAS  Google Scholar 

  • Voutilainen M, Sokka T, Juhola M, Färkkilä M, Hannonen P (1998) Nonsteroidal anti-inflammatory drug-associated upper gastrointestinal lesions in rheumatoid arthritis patients. Relationships to gastric histology, Helicobacter pylori infection, and other risk factors for peptic ulcer. Scand J Gastroenterol 33:811–816

    PubMed  CAS  Google Scholar 

  • Walson PD, Galletta G, Braden NJ, Alexander L (1989) Ibuprofen, acetaminophen, and placebo treatment of febrile children. Clin Pharmacol Ther 46:9–17

    Article  PubMed  CAS  Google Scholar 

  • Warrington SJ, Halsey A, O’Donnell L (1982) A comparison of gastrointestinal bleeding in healthy volunteers treated with tiaprofenic acid, aspirin or ibuprofen. Rheumatology 7:107–110

    CAS  Google Scholar 

  • Wolfe MM (2003) Risk factors associated with the development of gastroduodenal ulcers due to the use of NSAIDs. Int J Clin Pract Suppl 135:32–37

    PubMed  Google Scholar 

  • Wolfe MM, Lichtenstein DR, Singh G (1999) Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. N Engl J Med 340:1888–1899

    Article  PubMed  CAS  Google Scholar 

  • Kean WF, Buchanan WW (1987) Antirheumatic drug therapy in the elderly: a case of failure to identify the correct issues? J Am Geriatr Soc 35:363–364

    PubMed  CAS  Google Scholar 

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  1. Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK

    K. D. Rainsford

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Rainsford, K.D. (2012). Gastro-Intestinal Toxicity. In: Ibuprofen: Pharmacology, Therapeutics and Side Effects. Springer, Basel. https://doi.org/10.1007/978-3-0348-0496-7_7

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