Prolonged-release mesalazine: a review of its therapeutic potential in ulcerative colitis and Crohn's disease.
Prolonged-release mesalazine (Pentasa) consists of ethylcellulose-coated microgranules from which mesalazine (known in the US as mesalamine) is released in the small and large intestine in a diffusion-dependent manner. Dose-dependent improvements in clinical and endoscopic parameters have been reported with prolonged-release mesalazine 2 and 4 g/day in clinical trials in patients with mild to moderately active ulcerative colitis. Induction of clinical and endoscopic remission was achieved in more patients receiving a daily dosage of 4 g/day than in those receiving placebo. In patients with ulcerative colitis in remission, prolonged-release mesalazine is effective in reducing the rate of relapse. Higher dosages tend to be more effective, and a 12-month remission rate of 64% has been reported for patients treated with a 4 g daily dosage of this formulation. Comparative data indicate that prolonged-release mesalazine has similar efficacy in maintaining remission to molar equivalent doses of sulfasalazine. Data from a study in patients with mild to moderately active Crohn's disease indicates that higher dosages (4 g/day) of prolonged-release mesalazine are more effective than placebo in reducing disease activity. After 16 weeks' treatment, 64% of patients receiving a 4 g/day dosage experienced clinical improvement and 43% attained remission. In studies of patients in remission of Crohn's disease, the formulation appears to be more effective in preventing relapse in patients with isolated small bowel disease than in those with colonic involvement. The tolerability profile of oral prolonged-release mesalazine is similar to that of placebo and the incidence of adverse events does not appear to be dose-related. Nausea/vomiting, diarrhoea, abdominal pain and dyspepsia occur most frequently, although their incidence is low. Reports of nephrotoxicity during prolonged-release mesalazine treatment are rare.


CONCLUSIONS
Oral prolonged-release mesalazine is effective for maintenance and induction of remission of mild to moderately active colitis, both in patients with distal disease and in those with pancolitis. The formulation has similar efficacy to that of equimolar concentrations of sulfasalazine. Prolonged-release mesalazine also appears to be effective in the treatment of Crohn's disease, and maintenance therapy is of particular value in patients with isolated small bowel involvement. Evidence suggests that higher dosages (3 to 4 g/day) of prolonged-release mesalazine have additional therapeutic benefits over lower dosages in patients with inflammatory bowel disease without increasing the incidence of adverse events.
Clemett
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Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail@adis.co.nz
Markham
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000523:psychology; D003424:Crohn Disease / Q000188:drug therapy* / Q000523:psychology; D003692:Delayed-Action Preparations; D006801:Humans; D019804:Mesalamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D019804:Mesalamine