Tegaserod in the treatment of irritable bowel syndrome (IBS) with constipation as the prime symptom

Abstract

Irritable bowel syndrome with constipation (IBS-C) as the predominant bowel symptom is a prevalent disorder, characterized by recurring abdominal pain/discomfort, bloating, and constipation, and imposes a significant socio-economic burden. Traditional treatments generally address just one of the multiple IBS symptoms. The efficacy and safety profile of tegaserod, a serotonin 5-HT 4 receptor agonist, has been demonstrated in several randomized, placebo-controlled, and open-label trials. This review discusses the major clinical trials of tegaserod, which have involved 8948 IBS patients. Overall, data reveal that tegaserod is an effective treatment for IBS-C, providing statistically significant relief of overall and multiple individual IBS-C symptoms (abdominal pain/discomfort, bloating, and constipation) in both placebo-controlled and "real-life" open-label settings. Repeat treatments with tegaserod were also shown to be effective, which is noteworthy given the chronic and episodic nature of IBS. Moreover, tegaserod was associated with improvements in patients' quality of life and work productivity. Data also indicate that tegaserod is well tolerated over the short-term (4 weeks), long-term (12 months), and repeated treatments. Diarrhea is the only adverse event consistently associated with tegaserod and was generally mild and transient. Overall, tegaserod has been demonstrated to offer effective and well-tolerated treatment of IBS-C, providing patients with meaningful symptom relief.

Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral pain

“…In clinical studies, 5‐HT 4 receptor agonists have proven therapeutic potential to treat patients with GI motility disorders, but their lack of selectivity associated with adverse cardiovascular events, have limited their success. The partial 5‐HT 4 receptor agonist and prokinetic agent tegaserod maleate (Zelnorm ® ; Novartis, Basle, Switzerland) had shown some improvement in abdominal pain and discomfort, but this FDA‐approved drug was withdrawn from the market in 2007 due to a small, but statistically significant increase in the incidence of cardiovascular events 9 …”

“…Moreover, a common finding in IBS patients is symptom exacerbation in response to psychological and physical stressors, which induce increases in the perceptual response to rectosigmoid distension 7,8 . Drug development strategies for CIC as well as for IBS‐C indications have targeted several receptors that are expressed on the apical surface of GI epithelial cells, such as the 5‐hydroxytryptamine 4 (5‐HT 4 ) and type 2 chloride channel receptors 9,10 . Therapeutic targets for CIC and IBS‐C have primarily focused on the stimulation of GI motor function and increased water secretion into the intestinal lumen, but effective treatments that focus on multiple components are still limited.…”

Irritable bowel syndrome - from etiopathogenesis to therapy

“…Bloating or a feeling of abdominal distension are very frequent complaints in IBS and may be included in the diagnostic criteria for IBS in the future. Bloating is an important symptom of IBS and must be part both of the symptom complex and of the outcome measures of drug trials 42 . Most adults with the condition, experience episodes of symptom exacerbation, followed by periods of remission.…”

Pharmacotherapy for Irritable Bowel Syndrome

“…As a class, 5-HT 4 receptor agonists have demonstrated efficacy in patients with IBS-C. In a summary analysis of the major trials of tegaserod in patients with IBS in whom constipation was the predominant symptom, Layer et al evaluated major clinical trials of tegaserod, which involved 8948 IBS patients [ 93 ]. Tegaserod was an effective treatment for IBS-C, providing statistically significant relief of overall and multiple individual IBS-C symptoms (abdominal pain/discomfort, bloating, and constipation) in both placebo-controlled and open-label settings.…”