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Drugs Apr 2000Prolonged-release mesalazine (Pentasa) consists of ethylcellulose-coated microgranules from which mesalazine (known in the US as mesalamine) is released in the small and... (Review)
Review
UNLABELLED
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.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Crohn Disease; Delayed-Action Preparations; Humans; Mesalamine
PubMed: 10804042
DOI: 10.2165/00003495-200059040-00016 -
Der Internist Jul 2017Increasing interest in diverticular disease by the scientific community in the last 10-15 years has resulted in an increased number of publications. Among other things,... (Review)
Review
Increasing interest in diverticular disease by the scientific community in the last 10-15 years has resulted in an increased number of publications. Among other things, nonevidence-based therapeutic paradigms were tested in randomized, controlled therapy studies. The importance of surgery in the therapy of diverticulitis has diminished in recent years; in particular, it has no role in the treatment of diverticulitis types 1a, 1b, and 2a according to the Classification of Diverticular Disease (CDD) treated successfully by conservative means. Surgery has only a subordinate role in recurrent type 3b diverticulitis according to the CDD. Diverticulitis is therefore increasingly treated using conservative or drug therapy. However, only the classic, established antibiotics are currently available as effective drugs for the treatment of diverticular disease. However, these are also decreasing in significance. Over 90% of patients with type 1a/1b diverticulitis can be safely treated according to current data without the use of antibiotics. It is possible that type 2a diverticulitis will also be successfully treated without antibiotics in the future. Substances such as rifaximin, mesalazine, or probiotics, which were tested above all in patients with chronic recurrent forms (CDD type 3a/3b), have not yet been established.
Topics: Anti-Bacterial Agents; Conservative Treatment; Diverticulitis; Humans; Mesalamine; Probiotics; Randomized Controlled Trials as Topic; Rifamycins; Rifaximin
PubMed: 28608124
DOI: 10.1007/s00108-017-0266-4 -
Orvosi Hetilap Mar 20095-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents is commercially available, including azo-bond... (Review)
Review
5-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents is commercially available, including azo-bond pro-drugs such as sulfasalazine, olsalazine and balsalazide, and delayed- and controlled-release forms of mesalazine. In addition, the effectiveness of oral therapy relies on good compliance, which may be adversely affected by frequent daily dosing and a large number of tablets. Furthermore, poor adherence has been shown to be an important barrier to successful management of patients with UC. Recently, new, once-daily formulations of mesalazine including the unique multi-matrix delivery system and mesalazine granules were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of low pill burden and may contribute to increased long-term compliance and treatment success in clinical practice and might potentially further contribute to a decline in the risk for UC-associated colon cancers. In this systematic review, the authors summarize the available literature on the short- and medium-term efficacy and safety of the new once-daily mesalazine formulations.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Drug Administration Schedule; Humans; Medication Adherence; Mesalamine; Remission Induction; Severity of Illness Index
PubMed: 19228568
DOI: 10.1556/OH.2009.28555 -
Journal of Clinical Gastroenterology Feb 2001
Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Crohn Disease; Humans; Kidney Function Tests; Mesalamine; Nephritis, Interstitial
PubMed: 11205663
DOI: 10.1097/00004836-200102000-00002 -
Alimentary Pharmacology & Therapeutics Aug 2013Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. (Randomized Controlled Trial)
Randomized Controlled Trial
Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.
BACKGROUND
Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis.
AIM
To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions.
METHODS
This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks.
RESULTS
The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P < 0.0001, chi-squared test). For proctitis, the endoscopic remission rates after 4 weeks were 83.8% and 36.1% in the mesalazine and placebo suppository groups, respectively, and the corresponding rates for all other types of UC were 78.6% and 21.4%, respectively. The superiority of mesalazine to placebo was confirmed in both subgroups (P < 0.0001, Fisher's exact test). The percentage of patients without bleeding was significantly higher in the mesalazine group than the placebo group from Day 3 of treatment (P = 0.0001, Fisher's exact test).
CONCLUSIONS
The effectiveness of mesalazine suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421).
Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Asian People; Colitis, Ulcerative; Double-Blind Method; Female; Humans; Inflammation; Male; Mesalamine; Middle Aged; Proctitis; Suppositories; Treatment Outcome; Young Adult
PubMed: 23734840
DOI: 10.1111/apt.12362 -
Alimentary Pharmacology & Therapeutics Sep 2006The effectiveness of sulfasalazine depends on the splitting of the diazo bond in the molecule by the action of bacteria in the large bowel, releasing the... (Review)
Review
The effectiveness of sulfasalazine depends on the splitting of the diazo bond in the molecule by the action of bacteria in the large bowel, releasing the pharmacologically active moiety, 5-aminosalicylic acid. The development of pH-dependent, delayed-release formulations of 5-aminosalicylic acid abolished the toxicity associated with the sulfapyridine part of sulfasalazine. 5-aminosalicylic acid is now believed to act by activating a class of nuclear receptors involved in the control of inflammation, cell proliferation, apoptosis and metabolic function, the gamma form of peroxisome proliferator-activated receptors. These receptors are expressed at particularly high levels in colon epithelial cells, where their expression appears to be at least in part stimulated by gut bacteria. Other drugs known to act via peroxisome proliferator-activated receptor-gamma, such as rosiglitazone and the selective peroxisome proliferator-activated receptor-gamma ligand GW1929, can be displaced from their binding sites on the peroxisome proliferator-activated receptor-gamma molecule by 5-aminosalicylic acid at concentrations of 5-aminosalicylic acid that correspond with the concentrations found in the lumen of ulcerative colitis patients taking oral mesalazine. Genetically engineered heterozygous knockout mice (peroxisome proliferator-activated receptor-gamma+/-) are particularly susceptible to colonic inflammation, and inflammation is more severe in these mice, in response to chemicals that induce experimental colonic ulcers. In these experimental models, 5-aminosalicylic acid is ineffective in peroxisome proliferator-activated receptor-gamma+/- mice. This new insight provides a mechanistic foundation for the possibility that long-term treatment with 5-aminosalicylic acid can reduce the risk of colorectal cancer in patients with ulcerative colitis.
Topics: Acetylation; Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Colon; Delayed-Action Preparations; Humans; Mesalamine; Mice; Patient Compliance; Peroxisome Proliferator-Activated Receptors; Sulfasalazine
PubMed: 16939423
DOI: 10.1111/j.1365-2036.2006.03069.x -
Drugs Mar 1999Oral 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... (Review)
Review
UNLABELLED
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 delayed-release 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 delayed-release 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.
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Colitis, Ulcerative; Crohn Disease; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Eicosanoids; Humans; Mesalamine; Randomized Controlled Trials as Topic; Tissue Distribution
PubMed: 10193690
DOI: 10.2165/00003495-199957030-00013 -
Journal of Clinical Gastroenterology Feb 2001Mesalamines are slow-release formulations of 5-aminosalicylic acid (5-ASA) and are effective as primary treatment and maintenance therapy in inflammatory bowel disease....
Mesalamines are slow-release formulations of 5-aminosalicylic acid (5-ASA) and are effective as primary treatment and maintenance therapy in inflammatory bowel disease. Interstitial nephritis is a recognized side effect. We report two cases of biopsy-confirmed interstitial nephritis in patients being treated with 5-ASA. Both had a trial of steroid therapy. One patient had partial recovery of renal function but the other patient was in chronic renal failure and likely was approaching the need for dialysis. Interstitial nephritis is an under-recognized complication of 5-ASA therapy. Early identification and withdrawal of this drug can lead to a partial or complete reversal of renal dysfunction.
Topics: Adult; Biopsy; Colitis, Ulcerative; Crohn Disease; Female; Humans; Kidney; Mesalamine; Middle Aged; Nephritis, Interstitial
PubMed: 11205659
DOI: 10.1097/00004836-200102000-00019 -
Alimentary Pharmacology & Therapeutics Jan 2003: To quantify through systematic review the pharmacokinetic profiles of the oral delayed release and sustained release mesalazine (5-aminosalicylate, 5ASA) formulations... (Review)
Review
AIM
: To quantify through systematic review the pharmacokinetic profiles of the oral delayed release and sustained release mesalazine (5-aminosalicylate, 5ASA) formulations (Asacol, Salofalk, Mesasal, Claversal, Pentasa) and pro-drugs (sulfasalazine, olsalazine, balsalazide) used in the management of ulcerative colitis.
METHODS
: Selected articles had: (1) adult healthy volunteers or patients with ulcerative colitis and (2) quantification of pharmacokinetic data to include, at a minimum, urinary excretion of total 5ASA [5ASA plus N-Acetyl-5ASA (N-Ac-5ASA)].
DATA COLLECTION AND ANALYSIS
: Pharmacokinetic data (Tmax, Cmax, AUC, urinary excretion, faecal excretion) of 5ASA, its major metabolite N-Acetyl-5ASA, total 5ASA, and the parent pro-drug compounds was extracted.
MAIN RESULTS
: The summary results for urinary excretion of total 5ASA over 24-96 h in all subjects (either mean or median) were: sulfasalazine mean 11-33% or median 22%; olsalazine mean 14-31% or median 16-27%; balsalazide mean 12-35% or median 20%; Asacol mean 10-35% or median 18-40%; Pentasa mean 15-53% or median 23-34%; Salofalk, Mesasal and Claversal mean 27-56% or median 31-44%. The summary results for faecal excretion of total 5ASA over 24-96 h in all subjects (either mean or median) were: sulfasalazine mean 23-75% or median 38%; olsalazine mean 47-50% or median 17-36%; balsalazide mean 46% or median 22%; Asacol mean 40-64% or median 20-56%; Pentasa mean 12-51% or median 39-59%; Salofalk, Mesasal and Claversal mean 37-44% or median 23-35%.
CONCLUSIONS
: The systemic exposure to 5ASA, as measured by urinary excretion of total 5ASA, and the faecal excretion of total 5ASA is comparable for all oral mesalazine formulations and pro-drugs. Thus, selection of a mesalazine therapy for the treatment of ulcerative colitis should be based on other factors such as efficacy, dose-response, toxicity of the parent compound and its metabolites, compliance issues related to dose forms and dosing schedules, and costs.
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Feces; Humans; Mesalamine; Prodrugs
PubMed: 12492730
DOI: 10.1046/j.1365-2036.2003.01408.x -
Digestive Diseases and Sciences Apr 20095-Aminosalicylates are the standard treatment for induction and maintenance of remission in mild-to-moderate ulcerative colitis. In recent years, the 5-aminosalicylic... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
5-Aminosalicylates are the standard treatment for induction and maintenance of remission in mild-to-moderate ulcerative colitis. In recent years, the 5-aminosalicylic acid-containing pro-drug balsalazide has been the focus of attention.
AIM
To compare the efficacy and tolerance of balsalazide and mesalazine by meta-analysis.
METHODS
Pubmed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies comparing the efficacy and/or tolerance of balsalazide with mesalazine in the management of UC. The search terms were: "mesalazine" or "5-aminosalicylic acid" and "balsalazide" and "ulcerative colitis." Data were collected from 1966 to 2007 (up to February). There was no language restriction. "Symptomatic remission," "complete remission," "relapse rate," "total adverse events," and "withdrawals because of adverse events" were the key outcomes of interest.
RESULTS
Six randomized placebo-controlled clinical trials met our criteria and were included in the meta-analysis. In these "symptomatic remission," "complete remission," "relapse rate," "total adverse events," and "withdrawals because of adverse events" were evaluated in three, three, two, five, and six of the trials, respectively. They included 653 patients consisting of 55.4% men and 44.6% women randomized to receive either balsalazide or mesalazine. Pooling of three trials for symptomatic remission yielded a significant relative risk (RR) of 1.23 (95% confidence interval of 1.03-1.47, P = 0.02). The summary RR for complete remission in three trials was 1.3 (95% CI of 1.002-1.68, P = 0.048). Pooling of two trials for the outcome of relapse yielded a non-significant RR of 0.77 (95% CI of 0.56-1.07, P = 0.12). Pooling five studies from which data for any adverse events were extracted, yielded a non-significant RR of 0.87 (95% CI of 0.75-1.001, P = 0.53). The summary RR for withdrawals because of adverse events in six trials was 0.69, a non-significant RR (95% CI of 0.37-1.29, P = 0.24).
CONCLUSION
Balsalazide is more effective than mesalazine in induction of remission, but balsalazide has no benefit compared with mesalazine in preventing relapse in the population selected. The number of patients with any adverse events and withdrawals because of severe adverse events is similar for mesalazine and balsalazide.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Female; Humans; Male; Mesalamine; Phenylhydrazines; Remission Induction
PubMed: 18683049
DOI: 10.1007/s10620-008-0428-2