Skip to main content
SpringerLink
Log in

Tolerability of Aminosalicylates in Inflammatory Bowel Disease

  • Review Article
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

Since its synthesis in the 1930s and subsequent introduction, sulfasalazine has been an effective treatment for inflammatory bowel disease. However, up to one-third of patients are unable to take the drug because of severe intolerance. The finding in 1977 that the anticolitic effect of sulfasalazine lay in its 5-aminosalicylic [(5-ASA); mesalazine] moiety led to the development of new generations of 5-ASA agents.

These new agents include a slow continuous release formulation, pH-dependent release formulations, formulations using alternative carrier molecules and rectally administered formulations. Newer 5-ASA formulations are more effective than placebo in maintaining remission of ulcerative colitis. They have also been used for the treatment of active Crohn’s disease as well as maintenance treatment of ileocolonic Crohn’s disease, although their role in isolated small bowel disease is controversial. In general terms, all of the newer 5-ASA preparations are much better tolerated than sulfasalazine. The use of standard dosages of mesalazine in pregnancy appears to be tolerated; however, continuing surveillance of pregnancy outcome is recommended. While there is evidence that mesalazine can cause nephrotoxic reactions, these reactions can occur with all 5-ASA-containing preparations, particularly in individuals with existing renal disease. Blood dyscrasias can also occur with all aminosalicylates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I

Similar content being viewed by others

Notes

  1. Use of tradenames is for identification purposes only and does not imply endorsement.

References

  1. Svartz N. Sulfasalazine: 11. Some notes on the discovery and development of Salazopyrin. Am J Gastroenterol 1998; 83: 497–503

    Google Scholar 

  2. Baron JH, Connell PM, Lennard-Jones JE, et al. Sulphasalazine and salicylazosulphadimidine in ulcerative colitis. Lancet 1962; 1: 1094

    Article  PubMed  CAS  Google Scholar 

  3. Misiewicz JJ, Lennard-Jones JE, Connell AM, et al. Controlled trial of sulphasalazine in maintenance therapy for UC, Lancet 1965; I: 185–8

    Article  Google Scholar 

  4. Green JRB, Swan CHJ, Rowlinson AE, et al. Sulphasalazine or high dose balsalazide to treat relapse in UC? Results of randomized trial [abstract]. Gastroenterology 1993 Apr; 104 (Suppl.): A709

    Google Scholar 

  5. Mansfield JC, Giaffer MH, Cann PA, et al. Is high dose balsalazide better than sulphasalazine in initial management of ulcerative colitis? [abstract]. Gut 1991 Oct; 32: 1217

    Google Scholar 

  6. Hanauer SB: Medical therapy in ulcerative colitis. In: Kirsner JB, Shorter RG, editors. Inflammatory bowel disease. 4th ed. Baltimore: Williams and Wilkins, 1995: 664–94

    Google Scholar 

  7. Rutgeerts P, Comparative efficacy of coated oral 5-ASA (Claversal) and sulphasalazine for maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 1989; 3: 183–91

    Article  PubMed  CAS  Google Scholar 

  8. Meyers S, Sachar BD, Present DH, et al. Olsalazine sodium in the treatment of active ulcerative colitis in patients intolerant to sulphasalazine. A prospective randomised, placebo-controlled doubl e blind, dose ranging clinical trial. Gastroenterology 1987; 93: 1255–62

    PubMed  CAS  Google Scholar 

  9. Riley SA, Mani V, Goodman MJ, et al. Comparison of delayed release 5-ASA (mesalazine) and sulphasalazine as maintenance treatment for patients with ulcerative colitis. Gastroenterology 1988; 94: 1383–9

    PubMed  CAS  Google Scholar 

  10. Summers RW, Switz DM, Sessions JR, et al. National Co-operative Crohn’s Disease Study: result of drug treatment. Gastroenterology 1979; 77: 847–69

    PubMed  CAS  Google Scholar 

  11. Rijk MC, van Hogezand RA, van Lier HJ, et al. Sulphasalazine and prednisolone compared with sulphasalazine for treating active Crohn’s disease. A double-blind, randomized, multicenter trial. Ann Intern Med 1991; 114: 445–50

    PubMed  CAS  Google Scholar 

  12. Azad Khan AK, Piris J, Truelove SC. An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet 1977; 2: 892–5

    Article  PubMed  CAS  Google Scholar 

  13. Gaginella TS, Walsh RE. Sulfasalazine: multiplicity of action. Dig Dis Sci 1992; 37: 801–12

    Article  PubMed  CAS  Google Scholar 

  14. Greenfield SM, Punchard NA, Teare JP, et al. Review article: the mode of action of the aminosalicylates in inflammatory bowel disease. Aliment Pharmacol Ther 1993; 7: 369–83

    Article  PubMed  CAS  Google Scholar 

  15. Das KM, Eastwood MA, McManus JP, et al. The metabolism of salicylazosulphapyridine in ulcerative colitis. 1. The relationship between metabolites and response to treatment in inpatients. Gut 1973; 14(8): 631–41

    Article  PubMed  CAS  Google Scholar 

  16. Das KM, Eastwood MA, McManus JP, et al. The role of the colon in the metabolism of salicylazosulphapyridine. Scand J Gastroenterol 1974; 9(2): 137–41

    PubMed  CAS  Google Scholar 

  17. Ligumski M, Karmeli F, Sharon P, et al. Enhanced thromboxane A2 and prostacyclin production by cultured rectal mucosa in ulcerative colitis and its inhibition by steroid and sulphasalazine: Gastroenterology 1981; 81(3): 444–9

    Google Scholar 

  18. Sharon P, Stenson WF. Enhanced synthesis of leukotriene B4 by colonic mucosa in IBD. Gastroenterology 1984; 86: 453–60

    PubMed  CAS  Google Scholar 

  19. Peskar BM, Dreyling KW, Peskar BA, et al. Enhanced formation of sulphopeptide-leukotriene in UC and Crohn’s disease: inhibition by sulphasalazine and 5-ASA. Agents Actions 1986; 18: 381–3

    Article  PubMed  CAS  Google Scholar 

  20. Wengrower D, Eliakim R, Karmeli F. Pathogenesis of UC [abstract]. Gastroenterology 1987; 92: [69]

    Google Scholar 

  21. Travis SPL, Jewell DP. Salicylates for ulcerative colitis; their mode of action. Pharmacol Ther 1994; 63: 135–61

    Article  PubMed  CAS  Google Scholar 

  22. Wahl C, Liptay S, Adler G, et al. Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. J Clin Invest 1998; 101: 1163–74

    Article  PubMed  CAS  Google Scholar 

  23. Taffet SL, Das KM. Sulphasalazine — adverse effects and desensitization. Dig Dis Sci 1983; 28(9): 833–42

    Article  PubMed  CAS  Google Scholar 

  24. O’Moran C, Smethurst P, Dore CJ, et al. Reversible male infertility due to sulphasalazine, studies in man and rat. Gut 1984; 25: 1078–84

    Article  Google Scholar 

  25. Das KM, Eastwood MA, McManus JP, et al. Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype. N Engl J Med 1973; 289: 491–5

    Article  PubMed  CAS  Google Scholar 

  26. Das KM, Eastwood MA. Acetylation polymorphism of sulfapyridine in patients with ulcerative colitis and Crohn’s disease. Clin Pharmacol Ther 1972; 18: 514–20

    Google Scholar 

  27. Ireland A, Priddle JD, Jewell DP. Acetylation of 5-ASA by isolated human colonie epithelial cell. Clin Sei 1990; 78: 105

    CAS  Google Scholar 

  28. Jamshidi K, Arlander T, Garcia MC, et al: Azulfidine agranulo-cytosis with bone marrow megakaryocytosis, histiocytosis, plasmacytosis. Minn Med 1972; 55: 545–8

    PubMed  CAS  Google Scholar 

  29. Springs AL, Smith RS, Griffith H, et al. Heinz body anaemia due to salisalazosulfapyridine. Lancet 1958: 1039–42

  30. Barbour VM, Williams PF. Nephrotic syndrome associated with sulphasalazine [letter]. BMJ 1990; 301: 818

    Article  PubMed  CAS  Google Scholar 

  31. Hanauer SB. Inflammatory bowel disease. N Engl J Med 1996; 334: 841–8

    Article  PubMed  CAS  Google Scholar 

  32. Lee FI, Jewell DP, Mani V, et al. A randomised trial comparing mesalazine and prednisolone foam enemas in patients with acute distal ulcerative colitis. Gut 1996; 38: 229–33

    Article  PubMed  CAS  Google Scholar 

  33. Sutherland L, Roth D, Beck P. Alternatives to sulfasalazine: a meta-analysis of 5-AS A in the treatment of ulcerative colitis. Inflamm Bowel Dis 1997; 3: 665–78

    Google Scholar 

  34. Green JBR, Lobo AJ, Holdsworth CD, et al. Balsalazide is more effective and better tolerated than mesalamine in acute ulcerative colitis. Gastroenterology 1998; 114: 15–22

    Article  PubMed  CAS  Google Scholar 

  35. Levine DS, Pruitt R, Riff D, et al. A multicentre double-blind dose-response trial of colazide and Asacol® for mild-moder-ately active ulcerative colitis [abstract]. Gastroenterology 1997; 112: A1026

    Google Scholar 

  36. Hanauer SB, Krawitt EL, Robinson M, et al. Longterm management of Crohn’s disease with mesalamine capsule (Pentasa®). Am J Gastroenterol 1993; 104: 1343–51

    Google Scholar 

  37. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-ASA therapy for mild to moderate active ulcerative colitis. A randomized study. N Engl J Med 1987; 317: 1625–9

    Article  PubMed  CAS  Google Scholar 

  38. Sutherland LR, Robinson M, Onstad G, et al. A double-blind, placebo-controlled multicentre study of the efficacy and safety of 5-ASA tablets in the treatment of ulcerative colitis. In: Falk Symposium 1990, no. 56: trends in inflammatory bowel disease therapy. Freiburg: Falk Foundation, 1990: 45

  39. Azad Khan AK, Howes DT, Piris J, et al. Optimum dose of SASP for the maintenance treatment in UC. Gut 1980; 21: 232–40

    Article  Google Scholar 

  40. Travis SP, Tysk C, De Silva HJ, et al. Optimum dose of olsalazine for maintaining remission in ulcerative colitis. Gut 1994; 35(9): 1282–6

    Article  PubMed  CAS  Google Scholar 

  41. Singleton JW, Hanauer SB, Gintick GL, et al. Mesalamine capsules for the treatment of active Crohn’s disease: result of a 16 weeks trial. Pentasa Crohn’s disease study. Gastroenterology 1993; 104: 1293–301

    PubMed  CAS  Google Scholar 

  42. Prantera C, Pallone F, Brunetti G, et al. Oral 5-aminosalicylic acid (Asacol) in the maintenance treatment of Crohn’s disease. Gastroenterology 1992; 103: 363–8

    PubMed  CAS  Google Scholar 

  43. Prantera C, Cottone M, Pallone F, et al. Mesalamine in the treatment of mild to moderate active Crohn’s ileitis: result of a randomized, multicentre trial. Gastroenterology 1999; 116: 521–6

    Article  PubMed  CAS  Google Scholar 

  44. Singleton J. Second trial of mesalazine therapy in the treatment of active Crohn’s disease. Gastroenterology 1994; 107(2): 632–3

    PubMed  CAS  Google Scholar 

  45. Thomsen OO, Cortot A, Jewell D, et al. A comparison of budesonide and mesalamine for active Crohn’s disease. N Engl J Med 1998; 339: 370–4

    Article  PubMed  CAS  Google Scholar 

  46. Messori A, Brignola C, Trallori G, et al. Effectiveness of 5-ASA for maintenance remission of inpatients with Crohn’s disease: a meta-analysis. Am J Gastroenterol 1994; 89: 692–8

    PubMed  CAS  Google Scholar 

  47. Camma C, Giunta M, Roselli M, et al. Mesalamine in the maintenance treatment of Crohn’s disease: a meta-analysis adjusted for confounding variables. Gastroenterology 1997; 113: 1465–73

    Article  PubMed  CAS  Google Scholar 

  48. Lochs H, Mayer M, Wolfgang E, et al. Prophylaxis of postoperative relapse in Crohn’s disease with mesalamine: European cooperative Crohn’s disease study VI. Gastroenterology 2000; 118: 264–73

    Article  PubMed  CAS  Google Scholar 

  49. Rao SS, Cann PA, Holdsworth CD. Clinical experience of the tolerance of of mesalazine and olsalazine in patients intolerant of sulphasalazine. Scand J Gastroenterol 1987; 22: 332–6

    Article  PubMed  CAS  Google Scholar 

  50. Riley SA, Mani V, Gooman MJ, et al. Comparison of delayed-release 5-aminosalicylic acid (mesalazine) and sulphasalazine as maintenance treatment for patients with ulcerative colitis. Gastroenterology 1998; 94: 1449–53

    Google Scholar 

  51. Hanauer SB, Schwartz J, Robinson M, et al. Mesalamine capsules for the treatment of active ulcerative colitis: result of a controlled trial. Am J Gastroenterol 1993; 88: 1188–97

    PubMed  CAS  Google Scholar 

  52. Jick H, Myers MW, Dean AD. The risk of sulphasalazine and mesalazine associated blood disorder. Pharmacotherapy 1995; 15(2): 176–81

    PubMed  CAS  Google Scholar 

  53. Giaffer MH, O’Brien CJ, Holdsworth CD. Clinical tolerance to three 5-ASA releasing preparations in patients with inflammatory bowel disease intolerant or allergic to sulphasalazine. Aliment Pharmacol Ther 1992; 6: 51–9

    Article  PubMed  CAS  Google Scholar 

  54. Ireland A, Priddle JD, Jewell DP. A controlled trial comparing olsalazine and SASP for the maintenance treatment of ulcerative colitis. Gut 1988; 29: 835–7

    Article  PubMed  CAS  Google Scholar 

  55. Laursen LS, Naesdal J, Bukhave K, et al. Disposition of 5-ASA by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentration, serum values and urinary excretion. Gut 1990; 31: 1271–6

    Article  Google Scholar 

  56. Sninsky CA, Cort DH, Shanahan F, et al. Oral mesalamine (Asacol®) for mild to moderate ulcerative colitis. A multicentre study. Ann Intern Med 1991; 115: 350–5

    PubMed  CAS  Google Scholar 

  57. Farup PG, Hovde O, Halvorsen FA, et al. Mesalazine suppositories versus hydrocortisone foam in patients with distal ulcerative colitis. A comparison of the efficacy and practicality of two topical treatment regimens. Scand J Gastroenterol 1995; 30(2): 164–70

    Article  PubMed  CAS  Google Scholar 

  58. Fedorkow DM, Persaud D, Nimord CA, et al. Inflammatory bowel disease: a controlled study of late pregnancy outcome. Am J Obstet Gynecol 1989; 160(4): 998–1001

    PubMed  CAS  Google Scholar 

  59. Baired DD, Narendranathan M, Sandier RS, et al. Increased risk of preterm birth for women with inflammatory bowel disease. Gastroenterology 1990; 99: 987–94

    Google Scholar 

  60. Mogadam M, Dobbins WO, Korelitz BL, et al. Pregnancy in inflammatory bowel disease: effect of sulphasalazine and corticosteroid on fetal outcome. Gastroenterology 1981; 80: 72–6

    PubMed  CAS  Google Scholar 

  61. Diav-citrin O, Park YH, Veerasuntharam G, et al. The safety of mesalamine in human pregnancy: a prospective controlled cohort study. Gastroenterology 1998; 114: 23–8

    Article  PubMed  CAS  Google Scholar 

  62. Colombel JF, Brabant G, Gubler MC, et al. Renal insufficiency in infants: side effect of prenatal exposure to mesalazine. Lancet 1994; 344: 620–1

    Article  PubMed  CAS  Google Scholar 

  63. Mehta RP. Acute interstitial nephritis. Can Med Assoc J 1990; 143: 1031–2

    CAS  Google Scholar 

  64. Novis BH, Korzets Z, Chen P, et al. Nephrotic syndrome after treatment with 5-ASA. BMJ 1988; 296: 1442

    Article  PubMed  CAS  Google Scholar 

  65. Ruf-Ballauf W, Hofstandter F, Krentz K, et al. Akute interstitielle Nephritis durch 5ASA. Internist (Berl) 1984; 30: 262–4

    Google Scholar 

  66. Henning HV, Meinhold J, Eisenhauer T, et al. Chronische instertitielle Nephritis nach Behandlung mit 5ASA. Dtsch Med Wochenschr 1989; 114: 1091

    PubMed  CAS  Google Scholar 

  67. Von Muhlendahl KE. Nephritis durch 5-Aminosalicylsaure. Dtsch Med Wochenschr 1989; 114: 236

    Article  Google Scholar 

  68. De Broe ME, Stolear JC, Nouwen EJ, et al. Aminosalicylic acid (5-ASA) and chronic tubulointerstitial nephritis in patients with chronic inflammatory bowel disease: is there a link? Nephrol Dial Transplant 1997; 12: 1839–41

    Article  Google Scholar 

  69. CSM/MCA. Current problems in pharmacovigilance. UK, 1993; 19: 6

    Google Scholar 

  70. Amos RS, Pullar T, Bax D, et al. Sulfasalazine for rheumatoid arthritis: toxicity in 774 patients monitored for one to 11 years. BMJ 1986; 93: 420–3

    Article  Google Scholar 

  71. Keisu M, Ekman E. Sulphasalazine associated agranulocytosis in Sweden 1972-1989.Eur J Clin Pharmacol 1992; 43: 215–8

    Article  PubMed  CAS  Google Scholar 

  72. Dew MJ, Ebden P, Kidwai NS, et al. Comparison of the absorption and metabolism of sulphasalazine and acrylic-coated 5-ASA in normal subjects and patients with colitis. Br J Pharmacol 1984; 17: 474–6

    Article  CAS  Google Scholar 

  73. Pieniaszek HJ, Bates TR. Capacity limited gut wall metabolism of 5-aminosalicylic acid, a therapeutic active metabolite of sulphasalazine, in rats. J Pharmacol Sci 1979; 68: 1323–5

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Queen Elizabeth Hospital, Room 27A, Edgbaston, Birmingham, B15 2TH, England

    Sauid Ishaq

  2. North Staffordshire Hospitals, Stoke on Trent, England

    Jonathan R.B. Green

Authors
  1. Sauid Ishaq
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan R.B. Green
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sauid Ishaq.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ishaq, S., Green, J.R. Tolerability of Aminosalicylates in Inflammatory Bowel Disease. BioDrugs 15, 339–349 (2001). https://doi.org/10.2165/00063030-200115050-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00063030-200115050-00005

Keywords

Search

Navigation