Cardiac Safety Profiles of Patients Treated With Domperidone Using an FDA-Approved IND Protocol

Abstract

Introduction: Domperidone, a D2 receptor antagonist, has been used worldwide for chronic nausea and vomiting due to GI dysmotility disorders since 1974. However this drug is not approved by the FDA due to concerns of QT prolongation leading to torsade's de pointes, or sudden death. Its use in the USA is largely via compounding and online pharmacies and a few institutions that use an Investigational New Drug (IND ) protocol. Oral domperidone has been reported in some cases to prolong the QT interval and predispose to ventricular arrhythmias (Reddymasu et al. Am J Gastro 2007). Aim: 1.To analyze the EKG reports and the duration of QT intervals of patients on domperidone enrolled on an FDA approved IND protocol at our institution.2. To investigate possible cardiac side effects of domperidone. Methods: We are prospectively enrolling patients with nausea and vomiting due to gastroparesis not responding to standard therapy. Patients are excluded if they have significant cardiac diseases (venticular tachycardia or fibrillation; Torsades des pointes; sinus node dysfunction; or heart block) or use antiarrhythmic medications that can prolong the QT interval. Patients undergo EKG at baseline, 8 weeks, and 6 months. QTcB (Bazett) is used to assess the QTc interval with cutoffs for males and females of 450 and 470 milliseconds(ms), respectively. The starting dose for Domperidone in this study is 10mg TID and highest dose is 20mg QID. Patients are taken off protocol if they develop defined QTcB prolongation. Results: 21 patients have received domperidone. The median age is 49 years (27-64). They are primarily white (71%), females (86%) and 17/2 (81%) presented with a combination of nausea, vomiting, abdominal pain and or heartburn. All patients have gastroparesis. Median baseline EKG tracings are 419 ms( interquartile range: 411, 443). Median QTc for 14 patients at 8 weeks is 430 ms (397,438) corresponding to a median drop in QTc of 2ms (-6, 15) and a 0.5% increase over baseline. (table 1). Median time on study is 50.6 weeks. No chest pain, palpitations or other cardiac symptoms have been reported. No extrapyramidal side effects have been seen. No clinically significant QT prolongation has been seen and there are no reported arrhythmias or death during this study. Conclusion: Oral domperidone is a safe prokinetic drug in patients with chronic upper GI symptoms associated with gastroparesis. No clinically significant QT prolongation or cardiac side effects have been identified during the study.Table 1: EKG QTc Outcomes for 21 Patients Who Received Treatment