Skip to main content
SpringerLink
Log in

Oral Delayed-Release Mesalazine

A Review of its Use in Ulcerative Colitis and Crohn’s Disease

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Abstract

Oral delayed-release mesalazine is an enteric-coated formulation which releases mesalazine in the terminal ileum and colon.

Up to 74% of patients with mild to moderately active ulcerative colitis experience endoscopic or symptomatic improvement (including remission) or both when treated with oral delayed-release mesalazine 2.4 to 4.8 g/day. There is a trend towards a better response in patients receiving higher daily dosages of oral delayed-release mesalazine, especially in patients with active distal disease. In patients with left-sided ulcerative colitis, oral balsalazide 6.75 g/day appears to be more effective than oral delayed-release mesalazine 2.4 g/day, but a higher dosage of oral delayed-release mesalazine 4.8 g/day may provide additional benefit in these patients.

Oral delayed-release mesalazine 0.8 to 4.4 g/day appears to be as effective as sulfasalazine 2 to 4 g/day, prolonged-release mesalazine 1.5 g/day or balsalazide 3 g/day in maintaining remission in patients with ulcerative colitis. The optimal dosage of oral delayed-release mesalazine for the maintenance of remission is unclear. However, oral delayed-release mesalazine 1.6 g/day with rectal mesalazine 4g, administered twice weekly, was more effective than oral drug alone in maintaining remission in patients at high risk of relapse. In patients with left-sided or distal disease oral olsalazine 1 g/day appeared to be superior to oral delayedrelease mesalazine 1.2 g/day for maintenance of symptomatic remission.

Limited data in patients with Crohn’s disease have shown oral delayed-release mesalazine 0.4 to 4.8 g/day to be an effective therapy for active disease (remission in up to 45% of patients) and for quiescent disease (relapse in 34% of recipients over a duration of up to 12 months). Preliminary data indicate that oral delayedrelease mesalazine 2.4 g/day is effective in preventing postoperative recurrence of Crohn’s disease. Oral delayed-release mesalazine is effective and well tolerated in sulfasalazine-intolerant patients with ulcerative colitis or Crohn’s disease.

Conclusions: Oral delayed-release mesalazine is effective in patients with mild to moderately active or quiescent ulcerative colitis. Available data suggest that patients with left-sided or distal ulcerative colitis are likely to require higher daily dosages of oral delayed-release mesalazine or supplementation with rectal mesalazine. Oral delayed-release mesalazine also appears to be effective in active and quiescent Crohn’s disease. The drug is well tolerated and it appears to be effective in sulfasalazine-intolerant patients.

Mechanism of Action

Delayed-release mesalazine is coated with an 80 to 130μm layer of Eudragit® S, which dissolves at pH ≥7 and releases the active drug in the terminal ileum and colon.

Although the exact mechanism of action of mesalazine in patients with ulcerative colitis and Crohn’s disease is not known, in vitro studies have indicated various possible ways in which the drug may provide benefit in these patients. These include inhibition of eicosanoids, inhibition of cytokines and modulation of their effects and protection against oxygen-derived free radicals.

Most studies have shown that mesalazine concentration-dependently inhibits in vitro leukotriene (LT)B4 production in colonic mucosal cells from biopsy specimens from patients with inflammatory bowel disease and from patients with healthy colons, and in peripheral mononuclear leucocytes from healthy volunteers. Mesalazine did not affect in vitro prostaglandin (PG)E2 production in biopsy specimens from healthy volunteers but tended to normalise the increased PGE2 levels in biopsy specimens from patients with active ulcerative colitis. Other in vitro studies indicate that mesalazine may also decrease levels of LTC4, PGD2, 5-hydroxyeicosatetraenoic acid (HETE) and 11-, 12- and 15-HETE.

Mesalazine showed concentration-dependent inhibition of oxygen-derived free radical generation and concentration-dependent protection against oxidant-induced injury in various in vitro models.

Interferon (IFN)-γ binding and IFNγ-induced effects, such as expression of major histocompatibility gene complex D-related (HLA-DR) and increased cellular permeability, are also inhibited by mesalazine in cultures of standard colonic epithelial cell lines. Mesalazine may also decrease interleukin (IL)-1/1β and IL-2 production and reduce IL-2 receptor expression.

Pharmacokinetic Properties

Orally administered delayed-release mesalazine acts locally from within the lumen of the inflamed bowel and is partly absorbed into the systemic circulation. Mean steady-state mesalazine concentrations of 298.5 ng/mg wet tissue weight were found in ileocolonic biopsy specimen homogenates from patients with irritable bowel syndrome after 7 days’ treatment with oral delayed-release mesalazine 1.2 g/day. After 7 days’ treatment with other mesalazine formulations or prodrugs, containing nearly equal amounts of mesalazine, the tissue concentrations were 3-to 1000-fold lower than with oral delayed-release mesalazine. Rectal mucosal mesalazine concentrations increased dose-dependently after oral delayed-release mesalazine.

Mesalazine is primarily acetylated, to its major metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA), in the gut wall and the liver. After oral administration of delayed-release mesalazine, up to 44% of the administered dose is excreted in the faeces as mesalazine or Ac-5-ASA. Renal excretion of mesalazine and Ac-5-ASA accounts for up to 35.6% of the administered dose. The release of mesalazine after administration of oral delayed-release mesalazine does not appear to be affected by diarrhoea or by concurrent administration of omeprazole, famotidine or a high fibre diet with ispaghula husk.

Therapeutic Efficacy

Oral delayed-release mesalazine ≥2.4 g/day is generally effective in patients with mild to moderately active ulcerative colitis. Preliminary data indicate that oral delayed-release mesalazine 0.4 to 4.8 g/day is also effective in patients with active Crohn’s disease. Dosages ≤2.4 g/day are commonly used to maintain remission in patients with ulcerative colitis or Crohn’s disease. Oral delayed-release mesalazine appears to be effective in patients with sulfasalazine intolerance.

Oral delayed-release mesalazine 2.4 to 4.8 g/day led to endoscopie and/or symptomatic improvement (including remission) in up to 74% of patients with mild to moderately active ulcerative colitis. In 3 trials, patients receiving higher daily dosages of oral delayed-release mesalazine tended to experience greater improvement than those receiving lower daily dosages, especially in patients with active distal disease. Oral balsalazide 6.75 g/day was more effective than oral delayed-release mesalazine 2.4 g/day in inducing remission in patients with active, moderate to severe left-sided ulcerative colitis in one trial. Patients with left-sided disease were reported to be more resistant to treatment than those with extensive disease. However, endoscopic and symptomatic improvement in patients with left-sided disease was greater with oral delayed-release mesalazine 4.8 g/day than with 1.6 g/day, suggesting that higher dosages may offer additional benefit in these patients. Significantly greater numbers of patients with active distal disease receiving oral delayed-release mesalazine 2.4 g/day with mesalazine 4g rectal suspension enema once nightly showed symptomatic improvement than those receiving oral drug alone. Endoscopic and symptomatic improvement in patients with active distal disease receiving oral delayed-release mesalazine 3.2 g/day was similar to that in patients receiving prednisolone metabenzoate enema 20mg twice daily.

Relapse rates in patients with ulcerative colitis receiving oral delayed-release mesalazine 0.8 to 4.4 g/day (22 to 38% of patients) were similar to those with oral sulfasalazine 2 to 4 g/day, oral prolonged-release mesalazine 1.5 g/day or oral balsalazide 3 g/day in randomised, single- or double-blind trials of up to 12 months’ duration. The optimum dosage of oral delayed-release mesalazine for maintaining remission in patients with quiescent extensive ulcerative colitis remains unclear. Patients with left-sided or distal disease and those with short duration of remission may benefit from higher dosages of mesalazine. Oral administration of olsalazine 1 g/day (n = 42) appeared to be more effective than oral delayedrelease mesalazine 1.2 g/day (n = 40) in maintaining symptomatic remission in patients with left-sided ulcerative colitis (relapse in 12 vs 33% of patients). Oral delayed-release mesalazine 1.6 g/day with rectal mesalazine enema, 4g administered twice weekly, was significantly more effective than oral drug alone in preventing relapse over a period of 12 months in patients with ulcerative colitis at high risk of relapse (history of ≥2 relapses in the last 12 months).

There are limited data on the use of oral delayed-release mesalazine in patients with active or quiescent Crohn’s disease. Oral delayed-release mesalazine 3.2 g/day led to remission in 45% of recipients (n = 20) compared with similar improvement in 22% of placebo recipients (n = 18) in a trial in patients with mild to moderately active Crohn’s disease. 34% of patients with quiescent Crohn’s disease receiving oral delayed-release mesalazine 2.4 g/day relapsed during a 12-month trial period (versus 55% receiving placebo). Oral delayed-release mesalazine may be particularly effective in preventing symptomatic relapse in patients with Crohn’s disease restricted to the ileum and in those with mild disease. Endoscopic recurrence rates after 24 months, in patients with Crohn’s disease who underwent a first radical resection of the inflamed bowel, were significantly lower in oral delayed-release mesalazine 2.4 g/day recipients than in those who received no treatment (52 vs 85% of patients).

Tolerability

Oral delayed-release mesalazine appears to be well tolerated in patients who are intolerant to sulfasalazine. The incidence of gastrointestinal adverse events such as nausea, diarrhoea and dyspepsia, was greater with oral delayed-release mesalazine 1.6 or 2.4 g/day than with placebo in patients with mild to moderately active ulcerative colitis. The most common adverse events in patients treated with oral delayed-release mesalazine 2.4 g/day included headache, gas, nausea, diarrhoea and dyspepsia. Adverse events with oral delayed-release mesalazine 0.024 to 7.2 g/day necessitated drug withdrawal in up to 11% of patients in 3 large (n = 4717), prospective long term noncomparative trials. No serious adverse events were reported in these trials. The results of one retrospective trial indicate that oral delayed-release mesalazine 15 to 88 mg/kg is well tolerated in children, aged 4 to 19 years, with inflammatory bowel disease.

It has been estimated that serious renal impairment with oral delayed-release mesalazine will occur in fewer than 1 per 500 recipients. Early detection of renal impairment and prompt drug withdrawal (after ≤10 months of mesalazine administration) has been reported to lead to complete recovery of renal function in 5 of 6 patients. Available data suggest that all mesalazine-delivering drugs share the potential to cause nephrotoxicity, and monitoring of renal function of patients receiving these agents is recommended.

Ddosage and Administration

Oral delayed-release mesalazine 2.4 g/day, with concomitant corticosteroids where necessary, is recommended for the treatment of mild to moderately active ulcerative colitis in adults. However, oral delayed-release mesalazine has been used in daily doses of up to 4.8g in trials in patients with active, mild to moderate ulcerative colitis. For adult patients with quiescent ulcerative colitis, oral delayed-release mesalazine 1.2 to 2.4 g/day is recommended for maintenance of remission. However, depending on the duration of remission and the site of disease mesalazine may be used in dosages of up to 4 g/day in patients with quiescent ulcerative colitis.

No recommendations are available regarding the dosage of oral delayed-release mesalazine in patients with active Crohn’s disease. In patients with active Crohn’s disease, oral delayed-release mesalazine 3.2 g/day was more effective than placebo in inducing remission in one trial, but oral dosages ranging from 0.4 to 4.8 g/day have been used in other trials. Oral delayed-release mesalazine 1.2 to 2.4 g/day is recommended for the maintenance of remission in patients with Crohn’s ileo-colitis. The drug may be particularly effective in prolonging remission in patients with quiescent Crohn’s disease in whom the disease is restricted to the ileum or in those with mild disease.

Oral delayed-release mesalazine should not be used in patients with renal sensitivity to sulfasalazine or a history of hypersensitivity to salicylates, in patients with severe renal impairment or in children less than 2 years of age.

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

Similar content being viewed by others

References

  1. Riley SA. What dose of 5-aminosalicylic acid (mesalazine) in ulcerative colitis? Gut 1998; 42: 761–3

    Article  PubMed  CAS  Google Scholar 

  2. Geier DL, Miner Jr PB.New therapeutic agents in the treatment of inflammatory bowel disease. Am J Med 1992 Aug; 93: 199–208

    Article  PubMed  CAS  Google Scholar 

  3. Järnerot G. New salicylates as maintenance treatment in ulcerative colitis. Gut 1994 Sep; 35: 1155–8

    Article  PubMed  Google Scholar 

  4. Lauritsen K, Laursen LS, Rask-Madsen J. Clinical pharmacokinetics of drugs used in the treatment of gastrointestinal diseases (Part II). Clin Pharmacokinet 1990 Aug; 19: 94–125

    Article  PubMed  CAS  Google Scholar 

  5. Osterwald HP. Pharmaceutic development: mesalazine. Scand J Gastroenterol 1990; 25 Suppl. 172: 43–6

    Article  Google Scholar 

  6. Gionchetti P, Campieri M, Venturi A, et al. Systemic availability of 5-aminosalicylic acid: comparison of delayed release and an azo-bond preparation. Aliment Pharmacol Ther 1996; 10: 601–5

    Article  PubMed  CAS  Google Scholar 

  7. Rijk MCM, Van Schaik A, Van Tongeren JHM. Disposition of mesalazine from mesalazine-delivering drugs in patients with inflammatory bowel disease, with and without diarrhoea. Scand J Gastroenterol 1992 Oct; 27: 863–8

    Article  PubMed  CAS  Google Scholar 

  8. Christensen LA, Fallingborg J, Abildgaard K, et al. Topical and systemic availability of 5-amino-salicylate: comparisons of three controlled release preparations in man. Aliment Pharmacol Ther 1990 Oct; 4: 523–33

    Article  PubMed  CAS  Google Scholar 

  9. Forbes A, Chadwick C. Mesalazine preparations [letter]. Lancet 1997 Nov 1; 350: 1329

    Article  PubMed  CAS  Google Scholar 

  10. Botoman VA, Bonner GF, Botoman DA. Management of inflammatory bowel disease. Am Fam Physician 1998; 57: 57–68

    PubMed  CAS  Google Scholar 

  11. Rhodes J, Thomas G, Evans BK. Inflammatory bowel disease management: some thoughts on future drug developments. Drugs 1997 Feb; 53: 189–94

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  13. 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 Aug; 7: 369–83

    Article  PubMed  CAS  Google Scholar 

  14. Harting JW. New developments in the pharmacotherapy of inflammatory bowel disease. Pharm Weekbl Sci 1992 Aug; 14: 275–86

    Article  PubMed  CAS  Google Scholar 

  15. Schmidt C, Fels T, Baumeister B, et al. The effect of 5-aminosalicylate and para-aminosalicylate on the synthesis of prostaglandin E2 and leukotriene B4 in isolated colonic mucosal cells. Curr Med Res Opin 1996; 13: 417–25

    Article  PubMed  CAS  Google Scholar 

  16. Eliakim R, Karmeli F, Chorev M, et al. Effect of drugs on colonic eicosanoid accumulation in active ulcerative colitis. Scand J Gastroenterol 1992 Nov; 27: 968–72

    Article  PubMed  CAS  Google Scholar 

  17. Fox C, Moore WC, Lichtenstein LM. Modulation of mediator release from human intestinal mast cells by sulfasalazine and 5-aminosalicyclic acid. Dig Dis Sci 1991 Feb; 36: 179–84

    Article  PubMed  CAS  Google Scholar 

  18. Horn H, Preclik G, Stange EF, et al. Modulation of arachidonic acid metabolism by olsalazine and other aminosalicylates in leukocytes. Scand J Gastroenterol 1991 Aug; 26: 867–79

    Article  PubMed  CAS  Google Scholar 

  19. Crotty B, Hoang P, Dalton HR, et al. Salicylates used in inflammatory bowel disease and colchicine impair interferon-γ induced HLA-DR expression. Gut 1992 Jan; 33: 59–64

    Article  PubMed  CAS  Google Scholar 

  20. Di Paolo MC, Merrett MN, Crotty B, et al. 5-Aminosalicylic acid inhibits the impaired epithelial barrier function induced by gamma interferon. Gut 1996 Jan; 38: 115–9

    Article  PubMed  CAS  Google Scholar 

  21. Crotty B, Rosenberg WMC, Aronson JK, et al. Inhibition of binding of interferon-γ to its receptor by salicylates used in inflammatory bowel disease. Gut 1992 Oct; 33: 1353–7

    Article  PubMed  CAS  Google Scholar 

  22. Mahida YR, Lamming CED, Gallagher A, et al. 5-Aminosalicylic acid is a potent inhibitor of interleukin 1 β production in organ culture of colonie biopsy specimens from patients with inflammatory bowel disease. Gut 1991 Jan; 32: 50–4

    Article  PubMed  CAS  Google Scholar 

  23. Gertner DJ, Rampton DS, de Nucci G, et al. Eicosanoid release by rectal mucosa in vitro in ulcerative colitis: effects of conventional and potential new therapies. Eur J Gastroenterol Hepatol 1992 Oct; 4: 837–41

    Google Scholar 

  24. Rachmilewitz D, Karmeli F, Schwartz LW, et al. Effect of aminophenols (5-ASA and 4-ASA) on colonic interleukin-1 generation. Gut 1992 Jul; 33: 929–32

    Article  PubMed  CAS  Google Scholar 

  25. Bruin KF, Hommes DW, Jansen J, et al. Modulation of cytokine release from human monocytes by drugs used in the therapy of inflammatory bowel diseases. Eur J Gastroenterol Hepatol 1995 Aug; 7: 791–5

    PubMed  CAS  Google Scholar 

  26. Stevens C, Lipman M, Fabry S, et al. 5-Aminosalicylic acid abrogates T-cell proliferation by blocking interleukin-2 production in peripheral blood mononuclear cells. J Pharmacol Exp Ther 1995 Jan; 272: 399–406

    PubMed  CAS  Google Scholar 

  27. Mazlam MZ, Montazeri G, Hodgson HJF. The effects of some anti-inflammatory agents on cytokine release from human monocytes in vitro. Eur J Gastroenterol Hepatol 1993 Jul; 5: 515–20

    Google Scholar 

  28. Gionchetti P, Guarnieri C, Campieri M, et al. Scavenger effect of sulfasalazine, 5-aminosalicylic acid, and olsalazine on superoxide radical generation. Dig Dis Sci 1991 Feb; 36: 174–8

    Article  PubMed  CAS  Google Scholar 

  29. Greenfield SM, Punchard NA, Thompson RPH. Inhibition of red cell membrane lipid peroxidation by sulphasalazine and 5-aminosalicyclic acid. Gut 1991 Oct; 32: 1156–9

    Article  PubMed  CAS  Google Scholar 

  30. Dallegri F, Ottonello L, Ballestero A, et al. Cytoprotection against neutrophil derived hypochlorous acid: a potential mechanism for the therapeutic action of 5-aminosalicylic acid in ulcerative colitis. Gut 1990 Feb; 31: 184–6

    Article  PubMed  CAS  Google Scholar 

  31. Sandoval M, Liu X, Mannick EE, et al. Peroxynitrite-induced apoptosis in human intestinal epithelial cells is attenuated by mesalamine. Gastroenterology 1997 Nov; 113: 1480–8

    Article  PubMed  CAS  Google Scholar 

  32. Laursen LS, Stokholm M, Bukhave K, et al. Disposition of 5-aminosalicylic acid by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentrations, serum values, and urinary excretion. Gut 1990 Nov; 31: 1271–6

    Article  Google Scholar 

  33. Raimundo AH, Evans DF, Rogers J, et al. Colonic pH in ulcerative colitis: relevance to mezalazine therapy [abstract no. 400]. Am J Gastroenterol 1993 Sep; 88: 1581

    Google Scholar 

  34. De Vos M, Verdievel H, Schoonjans R, et al. Concentrations of 5-ASA and Ac-5-ASA in human ileocolonic biopsy homogenates after oral 5-ASA preparations. Gut 1992 Oct; 33: 1338–42

    Article  PubMed  Google Scholar 

  35. Hussain F, Ajjan R, Trudgill N, et al. Dose loading with oral mesalazine-optimising drug concentrations in the mucosa [abstract]. Gastroenterology 1996 Apr; 110 Suppl.: A928

    Google Scholar 

  36. Hussain F, Ajjan R, Trudgill N, et al. Single and divided dose delayed-release mesalazine: are traditional dosing regime in IBD outmoded? [abstract]. Gastroenterology 1996 Apr; 110 Suppl.: A928

    Google Scholar 

  37. Bossi A, Gionchetti P, Campieri M, et al. Comparative pharmacokinetic study of two multiple and single unit controlled release oral dosage forms of 5-ASA [abstract]. Ital J Gastroenterol 1991 Dec; 23: 641

    Google Scholar 

  38. Corey AE, Rose GM, Conklin JD. Bioavailability of single and multiple doses of enteric-coated mesalamine and sulphasalazine. J Int Med Res 1990 Nov–Dec; 18: 441–53

    PubMed  CAS  Google Scholar 

  39. Hussain F, Ajjan R, Weir N, et al. Mesalazine release from coated tablets: effect of drugs which alter gastrointestinal PH [abstract]. Gastroenterology 1996 Apr; 110 Suppl.: A928

    Google Scholar 

  40. Wiltink EHH, Mulder CJJ, Stolk LML, et al. Absorption of oral mesalazine-containing preparations and the influence of famotidine on the absorption. Scand J Gastroenterol 1990; 25: 579–84

    Article  PubMed  CAS  Google Scholar 

  41. Riley SA, Tavares IA, Bishai PM, et al. Mesalazine release from coated tablets: effect of dietary fibre. Br J Clin Pharmacol 1991 Aug; 32: 248–50

    Article  PubMed  CAS  Google Scholar 

  42. Tzivras M, Konstandinidis A, Hatzis G, et al. Systemic absorption of 5-aminosalicylic acid in patients with inactive ulcerative colitis treated with olsalazine and mesalazine. Eur J Gastroenterol Hepatol 1997 Jul; 9: 729–30

    Article  PubMed  CAS  Google Scholar 

  43. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults. Am J Gastroenterol 1997 Feb; 92: 204–11

    PubMed  CAS  Google Scholar 

  44. Levine DS, Pruitt R, Riff D, et al. A multi-center, double-blind dose-response trial of Colazide® (balsalazide disodium) and Asacol® (mesalamine) for mild-moderately active ulcerative colitis. Gastroenterology 1997 Apr; 112 Suppl.: A1026

    Google Scholar 

  45. Green JRB, Lobo AJ, Holdsworth CD, et al. Balsalazide is more effective and better tolerated than mesalamine in the treatment of acute ulcerative colitits. Gastroenterology 1998 Jan; 114: 15–22

    Article  PubMed  CAS  Google Scholar 

  46. Miglioli M, Bianchi Porro G, Brunetti G, et al. Oral delayed-release mesalazine in the treatment of mild ulcerative colitis: a dose ranging study. Eur J Gastroenterol Hepatol 1990 Jun; 2: 229–34

    Google Scholar 

  47. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mild to moderately active ulcerative colitis: a randomized study. N Engl J Med 1987; 317: 1625–9

    Article  PubMed  CAS  Google Scholar 

  48. Sninsky CA, Cort DH, Shanahan F, et al. Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis: a multicenter study. Ann Intern Med 1991 Sep; 115: 350–5

    PubMed  CAS  Google Scholar 

  49. Safdi M, DeMicco M, Sninsky C, et al. A double-blind comparison of oral versus rectal mesalamine versus combination therapy in the treatment of distal ulcerative colitis. Am J Gastroenterol 1997 Oct; 92: 1867–71

    PubMed  CAS  Google Scholar 

  50. Cobden I, Al-Mardini H, Zaitoun A, et al. Is topical therapy necessary in acute distal colitis? Double-blind comparison of high-dose oral mesalazine versus steroid enemas in the treatment of active distal ulcerative colitis. Aliment Pharmacol Ther 1991 Oct; 5: 513–22

    Article  PubMed  CAS  Google Scholar 

  51. Green JRB, Gibson JA, Kerr GD, et al. Maintenance treatment with balsalazide provides more effective control of nocturnal symptoms of ulcerative colitis (UC) than delayed-release mesalazine [abstract no. TW167]. Gut 1998 Mar; 42 Suppl. 1:A42

    Article  Google Scholar 

  52. d’Albasio G, Pacini F, Camarri E, et al. Combined therapy with 5-aminosalicylic acid tablets and enemas for maintaining remission in ulcerative colitis: a randomized double-blind study. Am J Gastroenterol 1997 Jul; 92: 1143–7

    PubMed  Google Scholar 

  53. Courtney MG, Nunes DP, Bergin CF, et al. Randomised comparison of olsalazine and mesalazine in prevention of relapses in ulcerative colitis. Lancet 1992 May; 339: 1279–81

    Article  PubMed  CAS  Google Scholar 

  54. Mesalamine Study Group. An oral preparation of mesalamine as long-term maintenance therapy for ulcerative colitis: a randomised, placebo-controlled trial. Ann Intern Med 1996 Jan; 124: 204–11

    Google Scholar 

  55. Desideri S, Ardizzone S, Petrillo M, et al. Two different oral formulations of 5-amino-salicylic acid (5-ASA) in maintenance treatment of ulcerative colitis [abstract]. Ital J Gastroenterol 1991 Dec; 23: 643

    Google Scholar 

  56. Dew MJ, Hughes P, Harries AD, et al. Maintenance of remission in ulcerative colitis with oral preparation of 5-aminosalicylic acid. BMJ 1982; 285: 1012

    Article  PubMed  CAS  Google Scholar 

  57. Dew MJ, Harries AD, Evans N, et al. Maintenance of remission in ulcerative colitis with 5-amino salicylic acid in high doses by mouth. BMJ 1983; 287: 23–4

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  59. Nakshabendi IM, Duncan A, Russell RI. Is Asacol as effective as sulphasalazine in maintaining remission of Crohn’s disease and ulcerative colitis? Postgrad Med J 1992 Mar; 68: 189–91

    Article  PubMed  CAS  Google Scholar 

  60. Abenhaim L, Sutherland LR, Field LG, et al. Has the introduction of a new mesalamine containing compound altered the clinical course of ulcerative colitis patients? [abstract]. Gastroenterology 1996 Apr; 110 Suppl.: A850

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  62. Tremaine WJ, Schroeder KW, Harrison JM, et al. A randomized, double-blind, placebo-controlled trial of the oral mesalamine (5-ASA) preparation, Asacol, in the treatment of symptomatic Crohn’s colitis and ileocolitis. J Clin Gastroenterol 1994 Dec; 19: 278–82

    Article  PubMed  CAS  Google Scholar 

  63. 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 

  64. Caprilli R, Andreoli A, Capurso L, et al. Oral mesalazine (5-aminosalicylic acid; Asacol) for the prevention of post-operative recurrence of Crohn’s disease. Aliment Pharmacol Ther 1994 Feb; 8: 35–43

    Article  PubMed  CAS  Google Scholar 

  65. Faber SM, Korelitz BI. Experience with eudragit-S-coated mesalamine (Asacol) in inflammatory bowel disease: an open study. J Clin Gastroenterol 1993 Oct; 17: 213–8

    Article  PubMed  CAS  Google Scholar 

  66. Donald IP, Wilkinson SP The value of 5-aminosalicylic acid in inflammatory bowel disease for patients intolerant or allergic to sulphasalazine. Postgrad Med J 1985; 61: 1047–8

    Article  PubMed  CAS  Google Scholar 

  67. Barletti C, Sambataro A, Barbaro S, et al. Outcomes from a large clinical survey in 302 patients suffering from Crohn’s disease, treated with oral mesalazine (Asacol Rm) [abstract]. Ital J Gastroenterol 1991; 23: 647–8

    Google Scholar 

  68. Pruitt RE, Gremillion D, Herring R, et al. Safety and tolerance of oral 5-AS A (Asacol®) in the treatment of ulcerative colitis and Crohn’s disease: results of the US multicenter open-label study [abstract]. Gastroenterology 1991; 100(5) Suppl. Pt 2: A241

    Google Scholar 

  69. Hanauer S, Regalli G, Verst-Brasch C. Safety of long-term mesalamine in patients with inflammatory bowel disease [abstract no. 343]. Am J Gastroenterol 1996 Sep; 91: 1971

    Google Scholar 

  70. Schroeder KW, Tremaine WJ, Albrecht HH, et al. Safety of long-term mesalamine therapy in patients with inflammatory bowel disease [abstract]. Gastroenterology 1996 Apr; 110 Suppl.: A1011

    Google Scholar 

  71. Smith Kline & French Laboratories. Asacol® Data Sheet. Welwyn Garden City, Hertfordshire, England, 1997

  72. D’Agata ID, Vanounou T, Scidman EG. Mesalamine in pédiatrie inflammatory bowel disease: a 10 year experience [abstract]. Gastroenterology 1995 Apr; 108 Suppl.: A805

    Google Scholar 

  73. Pardi DS, Tremaine WJ, Sandborn WJ, et al. Renal and urologic complications of inflammatory bowel disease. Am J Gastroenterol 1998; 93: 504–14

    Article  PubMed  CAS  Google Scholar 

  74. Schreiber S, Hämling J, Zehnter E, et al. Renal tubular dysfunction in patients with inflammatory bowel disease treated with aminosalicylate. Gut 1997; 40: 761–6

    Article  PubMed  CAS  Google Scholar 

  75. Stretch GL, Campbell BJ, Dwarakanath AD, et al. 5-Amino salicylic acid absorption and metabolism in ulcerative colitis patients receiving maintenance sulphasalazine, olsalazine or mesalazine. Aliment Pharmacol Ther 1996 Dec; 10: 941–7

    Article  PubMed  CAS  Google Scholar 

  76. Hanauer SB, Verst-Brasch C, Regalli G. Renal safety of long-term mesalamine therapy in inflammatory bowel disease (IBD) [abstract]. Gastroenterology 1997 Apr; 112 Suppl.: A991

    Article  Google Scholar 

  77. Mani V. Mesalazine-associated interstitial nephritis [letter]. Nephrol Dial Transplant 1997 Mar; 12: 622

    Article  PubMed  CAS  Google Scholar 

  78. World MJ, Stevens PE, Ashton MA, et al. Mesalazine-associated interstitial nephritis. Nephrol Dial Transplant 1996 Apr; 11: 614–21

    Article  PubMed  CAS  Google Scholar 

  79. Popoola J, Muller AF, Pollock L, et al. Late onset interstitial nephritis associated with mesalazine treatment. BMJ 1998 Sep; 317: 795–7

    Article  PubMed  CAS  Google Scholar 

  80. Brouillard M, Gheerbrant JD, Gheysens Y, et al. Interstitial nephritis and mesalazine: three new cases [in French]. Gastroenterol Clin Biol 1998 Aug–Sep; 22: 724–6

    PubMed  CAS  Google Scholar 

  81. World MJ. Mesalazine-associated interstitial nephritis: reply [letter]. Nephrol Dial Transplant 1997 Mar; 12: 623

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  83. Dew MJ, Harries AD, Evans BK, et al. Treatment of ulcerative colitis with oral 5-aminosalicylic acid in patients unable to take sulphasalazine. Lancet 1983; II: 801

    Article  Google Scholar 

  84. Mulder CJJ, van den Hazel SJ. Drug therapy: dose-response relationship of oral mesalazine in inflammatory bowel disease. Mediat Inflamm 1998; 7: 135–6

    Article  CAS  Google Scholar 

  85. Ardizzone S, Molteni P, Bollani S, et al. Guidelines for the treatment of ulcerative colitis in remission. Eur J Gastroenterol Hepatol 1997 Sep; 9: 836–41

    Article  PubMed  CAS  Google Scholar 

  86. Sutherland LR, May GR, Shaffer EA. Sulfasalazine revisited: a meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitis. Ann Intern Med 1993 Apr; 118: 540–9

    PubMed  CAS  Google Scholar 

  87. British National Formulary. Mesalazine. Vol. 36. London: The Pharmaceutical Press. 1998 Sep

    Google Scholar 

  88. Murthy S, Flanigan A. Recent developments in inflammatory bowel disease therapy. Expert Opin Ther Pat 1997 Jul; 7: 695–715

    Article  CAS  Google Scholar 

  89. Gibson PR. Inflammatory bowel disease: current concepts in pathogenesis and therapy. Clin Immunother 1994 Aug; 2: 134–60

    Google Scholar 

  90. Ardizzone S, Bianchi Porro G. A practical guide to the management of distal ulcerative colitis. Drugs 1998 Apr; 55: 519–42

    Article  PubMed  CAS  Google Scholar 

  91. de Franchis R, Vecchi M, Carpinelli L, et al. Comparison of the efficacy and safety of sulphasalazine and mesalazines in the maintenance treatment of ulcerative colitis: a meta-analysis. Eur J Gastroenterol Hepatol 1993 Jul; 5: 505–10

    Google Scholar 

  92. Travis SPL, Tysk C, de Silva HJ, et al. Optimum dosage of olsalazine for maintaining remission in ulcerative colitis. Gut 1994; 35: 1282–6

    Article  PubMed  CAS  Google Scholar 

  93. Fockens P, Mulder CJJ, Tytgat GNJ, et al. Comparison of the efficacy and safety of 1.5 compared with 3.0g oral slow-release mesalazine (Pentasa) in the maintenance treatment of ulcerative colitis. Eur J Gastroenterol Hepatol 1995 Nov; 7: 1025–30

    Article  PubMed  CAS  Google Scholar 

  94. Camilla C, Giunta M, Rosselli 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  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Amitabh Prakash & Anthony Markham

Authors
  1. Amitabh Prakash
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anthony Markham
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amitabh Prakash.

Additional information

Various sections of the manuscript reviewed by: G. d’Albasio, Divisione di Gastroenterologia, Azienda Ospedaliera Careggi, Careggi, Florence, Italy; A. Forbes, St. Mark’s Academic Institute, St. Mark’s Hospital, Harrow, Middlesex, England; P. Gionchetti, Dipartimento di Medicina Interna e Gastroenterologia, Università di Bologna, Bologna, Italy; D.P. Jewell, Gastroenterology Unit, Department of Medicine, Radcliffe Infirmary, Oxford, England; J.M. Rhodes, Gastroenterology Research Group, University Clinical Department of Medicine, The University of Liverpool, Liverpool, England; G.N.J. Tytgat, Department of Gastroenterology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; M.J. World, Department of Military Medicine, Royal Defence Medical College, Gosport, England.

Data Selection

Sources: Medical literature published in any language since 1966 on delayed-release mesalazine, identified using AdisBase (a proprietary database of Adis International, Auckland, New Zealand), Medline and EMBASE. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: AdisBase search terms were ‘mesalazine’ and ‘inflammatory bowel disorders’. Medline and EMBASE search terms were ‘mesalazine’, ‘mesalamine’, ‘inflammatory bowel diseases’ and ‘inflammatory bowel disorders’. Searches were last updated 12 Jan 1999.

Selection: Studies in patients with ulcerative colitis or Crohn’s disease who received oral delayed-release mesalazine. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Oral delayed-release mesalazine, ulcerative colitis, Crohn’s disease, pharmacokinetics, pharmacodynamics, therapeutic use, tolerability, dosage and administration.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Prakash, A., Markham, A. Oral Delayed-Release Mesalazine. Drugs 57, 383–408 (1999). https://doi.org/10.2165/00003495-199957030-00013

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199957030-00013

Keywords

Search

Navigation