Patient considerations in the management of chronic constipation: focus on prucalopride

Andrea Shin Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA Abstract: Chronic constipation is a common condition that significantly impacts health care utilization, productivity, and quality of life. Laxatives are commonly used, although often insufficient in restoring normal bowel function or providing adequate relief. There remains a significant need for the development of novel agents to optimize treatment of this condition. This review provides an overview of the preclinical and clinical trial data, supporting the efficacy and safety of prucalopride, a highly selective 5-HT4 receptor agonist that has been approved by the European Medicine Agency for the treatment of chronic constipation in adults who have failed standard laxative therapy. Unlike older 5-HT4 agonists, prucalopride has not been associated with adverse cardiovascular side effects or QT prolongation owing to its high selectivity and affinity for the 5-HT4 receptor without clinically significant cross-reactivity at the human ether-à-go-go-related gene (hERG) potassium channel or 5-HT receptor subtypes that have previously been implicated in adverse cardiovascular events and arrhythmias. Careful safety assessments have documented the relative safety and tolerability of this agent in various patient groups. Focus has also been placed on demonstrating efficacy with regard to bowel function, symptoms, and patient-reported outcomes such as the Patient Assessment of Constipation-Symptoms and the Patient Assessment of Constipation Quality of Life scores to support the use of prucalopride as a safe and effective therapeutic option for the management of chronic constipation. Keywords: prucalopride, chronic constipation, 5-HT4 agonist, safety, prokinetic, PAC-QO