Olsalazine adverse effects

The use of non-sulfapyridine-based aminosalicylates has led to greater tolerability. Although the adverse effects are similar to those of sulfasalazine, they occur at a much lower rate. Olsalazine, in particular, is associated with a higher incidence of secretory diarrhea. These agents can also be used safely in patients with a reported sulfonamide allergy. 

Oral mesalamine derivatives may impose a lower frequency of adverse effects compared with sulfasalazine. Up to 90% of patients who are intolerant to sulfasalazine will tolerate oral mesalamine derivatives. Olsalazine may cause watery diarrhea in up to 25% of patients. 

Patients with frequent relapses despite apparently adequate prophylactic treatment should be reviewed carefully. Associated milk intolerance or coeliac disease need treatment on their merits. Colonoscopic evidence of dysplasia raises the question of undiagnosed malignancy. Occasionally the prophylactic agents themselves can cause watery diarrhoea (particularly olsalazine) or a hypersensitivity colitic disease. Prophylactic azathioprin should be considered in those in whom relapse is frequent despite use of aminosalicylates or if they are poorly tolerated. In the effective dose of 2 mg/kg adverse effects of bone marrow depression are uncommon, but still occur, and regular haematological review is essential (monthly or bi-monthly). Azathioprin-induced pancreatitis is an uncommon but well-recognised entity. 

In a 12-week trial in 168 patients with mild to moderate ulcerative colitis, olsalazine 3 g/day was as effective as mesalazine 3 g/day in inducing a remission (5). There were more adverse effects in patients taking olsalazine (41 of 88) than mesalazine (29 of 80). Most of the adverse effects related to bowel disturbances diarrhea, vomiting, abdominal discomfort, heartburn, flatulence, and nausea. Diarrhea was more common in patients taking olsalazine. One patient taking mesalazine developed a lupus-like syndrome. 

In a randomized, double-blind, placebo-controlled trial in 328 patients with quiescent Crohn s disease, olsalazine 2 g/day given for 52 weeks was not superior to placebo in maintaining remission (13). Gastrointestinal adverse effects were significantly more frequent in the olsalazine group diarrhea was the most commonly reported adverse effect. 

Crossover studies have shown that mesalazine has about a 10-fold lower potential than sulfasalazine for inducing allergic reactions or causing intolerance. Adverse effects with all aminosalicylates include (generally more frequent with sulfasalazine) headache, nausea, abdominal pain, dyspepsia, fatigue, rash, fever, rarely exacerbation of the disease, pancreatitis, pericarditis, pneumonitis, liver disease, nephritis, and bone marrow depression. Watery diarrhea is an adverse effect unique to olsalazine, while anorexia, folate malabsorption, hemolysis, neutropenia, agranulocytosis, male infertility, and neuropathy are unique to sulfasalazine. 

The adverse effects of olsalazine would be expected to be those of mesalazine, and this is largely the case. However, diarrhea has been sufficiently common to suggest that it may be a particular problem with olsalazine. 

Nephrotoxicity has been described during treatment with olsalazine (SEDA-21, 364). To assess the effects of 9 months of treatment with oral mesalazine 1.2 g/day and olsalazine 1 g/day on renal function, a randomized trial has been performed in 40 patients with ulcerative colitis in complete remission (91). Neither drug had a significant effect on glomerular filtration rate. Adverse effects (all mild to moderate) were more common in the mesalazine group they included abdominal pain and distension, dyspepsia, nausea, and diarrhea. 

Apart from classic analgesic nephropathy, this chapter will also handle the possible nephrotoxic role of 5-aminosalicylic acid (5-ASA) used in patients with chronic inflammatory bowel disease (IBD). During the last decade, 5-ASA replaced sulfasalazine as first-line therapy for mildly to moderately active IBD. For decades, sulphasalazine, an azo-compound derived from sulphapyridine and 5-aminosalicylic acid (5-ASA), has been the only valuable non-corticosteroid drug in the treatment of inflammatory bowel disease. Azad Kahn et al. [25] showed that the pharmacologically active moiety in sulphasalazine for the treatment of these diseases was 5-ASA. Consequently, this resulted in a number of new 5-ASA formulations (mesalazine, olsalazine, balsalazine) for topical and oral use. Since the metabolite sulphapyridine was largely responsible for the side effects of sulfasalazine, the primary advantage of the newer 5-ASA agents is their improved adverse effect profile. 

Sulfasalazine has been used for the management of RA and ankylosing spondylitis with apparently similar effectiveness as penicillamine and with less toxicity. While 5-aminosalicylic acid is the active agent in inflammatory bowel disease, it is believed that sulfapyridine is mostly responsible for the antirheumatoid effects. Gastrointestinal complaints, dizziness and photosensitivity are the most frequently observed adverse events. With levamisole and also with sulfasalazine and olsalazine a delay of 2-3 months is to be expected before positive responses will be observed. 

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