Narrative ReviewTegaserod: What’s Old Is New Again
Section snippets
Irritable Bowel Syndrome With Constipation: Major Impacts And Unmet Needs
Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction characterized by recurrent abdominal pain associated with altered bowel habits.1,2 Large population-based studies estimate a worldwide IBS prevalence of 5%–15% in developed countries, with a female predominance, and approximately one-third of IBS patients having IBS with a constipation-predominant bowel pattern (IBS-C).3, 4, 5 IBS imparts a substantial negative impact on the health-related quality of life of affected
5-HT4 Receptor Pharmacology
For 5-HT4 receptor pharmacology, see the Supplementary Materials.
Tegaserod Pharmacokinetics And Metabolism
For tegaserod pharmacokinetics and metabolism, see the Supplementary Materials.
Tegaserod Effects On Gi Function
For tegaserod effects on GI function, see the Supplementary Materials.
Tegaserod Phase II/III IBS-C Trial Summary
The initial studies evaluated a dose range of tegaserod and, based on these findings, the doses of 2 and 6 mg were selected for further evaluation.39 Two pivotal placebo-controlled 12-week studies were conducted in IBS-C patients, one evaluating both 2 and 6 mg twice daily doses in males and females40 and the other only evaluating 6 mg twice daily in females.41 The primary endpoint in these studies was the Subjective Global Assessment (SGA) of relief, assessed using a 5-point ordinal scale.42
Cisapride History
Cisapride was introduced worldwide in the 1990s as a serotonin 5-HT4 agonist with 5-HT3 antagonist activity (Supplementary Table 3) and was approved by the FDA for nocturnal heartburn but was widely used for the treatment of a wide range of motility disorders.21 However, it was eventually recognized that cisapride use could result in prolongation of the QT interval and thereby increase the risk of arrhythmia.47, 48, 49, 50 Because cisapride is metabolized by the cytochrome P450 enzyme system,
“New Again”: The Re-Emergence Of Tegaserod
In light of this constellation of data dispelling concern relating to potential serious adverse events, in 2018 a supplemental new drug application was submitted by Sloan Pharma to the U.S. FDA for tegaserod use in women with IBS-C and low CV risk.66 On October 17, 2018, an FDA and Gastrointestinal Drugs Advisory Committee meeting convened to perform a complete review of the tegaserod resubmission, including the available safety data.67 Members of that committee ultimately voted 11 to 1 in
Conclusions and Expert Opinion
The efficacy of tegaserod in the management of chronic constipation disorders, including the global abdominal symptoms of IBS, has been well established. With careful consideration of the potentially serious adverse events, in this current era the concerns relating to CV events and intestinal ischemia have been sufficiently, and convincingly, addressed to allow FDA reapproval for the use of this agent in IBS-C patients. Tegaserod overall is well tolerated, with treatment-related adverse events
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Tegaserod-induced myocardial infarction: case report and hypothesis
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Tegaserod maleate exhibits antileukemic activity by targeting TRPM8
2022, Biomedicine and PharmacotherapyCitation Excerpt :Our study evaluated the antileukemic activity of 2040 compounds at a single concentration using a large-scale screen in AML cell lines. Tegaserod maleate, a 5-hydroxytryptamine 4 (5-HT4) receptor partial agonist, has been approved for treating irritable bowel syndrome with constipation (IBS-C) [15–17]. None of the other 5-HT4 receptor agonists in the drug screening exhibited anti-AML effects, which prompted us to explore the mechanisms underlying the regulation of AML progression by tegaserod maleate.
Therapeutic cysteine protease inhibitors: a patent review (2018–present)
2024, Expert Opinion on Therapeutic PatentsPharmacological and nutritional therapy of children and adults with chronic intestinal pseudo-obstruction
2023, Expert Review of Gastroenterology and Hepatology
Conflicts of interest The authors disclose the following: Gregory Sayuk has served as a consultant for AbbVie (Allergan), Ironwood, Salix, and Alnylam; and served on the speakers bureau for AbbVie (Allergan), Ironwood, Salix, Alnylam, and the GI Health Foundation. Jan Tack has served as a consultant for Adare, AlfaWassermann, Allergan, Arena, Bayer, Christian Hansen, Clasado, Danone, Devintec, Falk, Grünenthal, Ironwood, Janssen, Kiowa Kirin, Menarini, Mylan, Neurogastrx, Neutec, Novartis, Noventure, Nutricia, Shionogi, Shire, Takeda, Theravance, Tramedico, Truvion, Tsumura, Zealand, and Zeria Pharmaceuticals; received research support from Shire, Sofar, and Tsumura, and served on the speakers bureau for Abbott, Allergan, AstraZeneca, Janssen, Kyowa Kirin, Menarini, Mylan, Novartis, Shire, Takeda, Truvion, and Zeria.