Clin Gastroenterol Hepatol. 2022 Feb 2;S1542-3565(22)00078-7.doi: 10.1016/j.cgh.2022.01.024. Online ahead of print.

Gregory S Sayuk ¹, Jan Tack ²

Author information

¹Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO USA; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO USA; St. Louis Veterans Affairs Medical Center, St. Louis, MO USA.

²TARGID (Translational Research Center for Gastrointestinal Disorders), University of Leuven, Leuven, Belgium; Rome Foundation for Disorders of Gut Brain Interactions (DGBIs); Institute of Medicine, University of Gothenburg, Sweden. Electronic address: jan.tack@kuleuven.be.

Abstract

Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are common gastrointestinal disorders imposing considerable impact on the quality of life and well-being of affected individuals. A paucity of evidence-based treatment options exist for CIC and IBS-C sufferers. Tegaserod, a 5-HT₄ agonist, has a substantial body of pre-clinical and clinical study evidence to support its beneficial role in modulating sensorimotor function of the luminal gastrointestinal tract. Tegaserod was first approved for use by the United States Food and Drug Administration (U.S. F.D.A.) for the management of IBS-C and CIC in 2002 and 2004, respectively. Tegaserod enjoyed a successful uptake in the management of these disorders during its first several years of availability in the U.S., but was later withdrawn from the market in 2007 over concerns related to adverse cardiovascular events. Since, additional safety data has been generated, and following a resubmission and review by the F.D.A., in April 2019 tegaserod was once again approved for use in IBS-C under a more restricted labeling, confining use to women under the age of 65 without heart disease or additional cardiovascular risk factors. This review summarizes the regulatory journey of tegaserod, and details the existing pharmacokinetic, physiologic, clinical, and safety data of tegaserod generated over the last two decades. The discussion also examines the future of tegaserod in the treatment of these constipation disorders, as well as its potential role in other related disorders of brain-gut interaction (DGBI).