Tegaserod: What's Old Is New Again

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 preclinical 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 U.S. Food and Drug Administration 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in the management of these disorders during its first several years of availability in the United States, but was later withdrawn from the market in 2007 over concerns related to adverse cardiovascular events. Since then, additional safety data has been generated, and following a resubmission and review by the Food and Drug Administration, in April 2019, tegaserod was once again approved for use in IBS-C under a more restricted labeling, confining use to women under 65 years of age 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 2 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.