Absence of QT prolongation after administration of a 24-mg bimodal-release ondansetron pill (RHB-102)

Am J Emerg Med. 2021 May:43:205-209. doi: 10.1016/j.ajem.2020.02.057. Epub 2020 Feb 26.

Abstract

Objectives: Prospective data evaluating the effect of ondansetron on the corrected QT (QTc) interval is lacking in emergency department clinical use. As part of a randomized trial of a 24-mg bimodal-release ondansetron (RHB-102) pill, we tested the effect of RHB-102 compared to placebo on QTc change.

Methods: This was a planned safety outcome analysis within a multicenter, double-blind, placebo-controlled trial. The trial compared the effects of RHB-102 among patients ≥12 years who presented to 21 centers with symptoms of acute gastroenteritis. Patients with an initial baseline electrocardiogram as well as a follow-up electrocardiogram 4 h later were included in the analysis. The safety endpoint for this analysis was the change from baseline in QTc interval at 4 h, the median time at which ondansetron serum level peaks.

Results: A total of 147 patients were included with a mean baseline QTc in the RHB-102 and placebo arms of 410 and 406 ms, respectively. There was no difference in the change in QTc at 4 h post-study drug administration between the RHB-102 (+4, 95% CI 1-8 ms) and placebo group (+5, 95% CI 1-9 ms). In the RHB-102 arm, 6.6% of patients had a QTc change >30 ms and in the placebo arm 3.6% (p = 0.48). No patient in either arm had a QTc change >60 ms after study drug administration.

Conclusion: In patients with normal baseline QTc, 24-mg bimodal-release ondansetron did not prolong the QTc in comparison to placebo.

Keywords: Gastroenteritis; Ondansetron; QTc prolongation.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Antiemetics / administration & dosage*
  • Antiemetics / adverse effects
  • Antiemetics / pharmacology
  • Delayed-Action Preparations / administration & dosage
  • Double-Blind Method
  • Emergency Service, Hospital / statistics & numerical data
  • Female
  • Gastroenteritis / drug therapy*
  • Humans
  • Long QT Syndrome / chemically induced*
  • Male
  • Off-Label Use
  • Ondansetron / administration & dosage*
  • Ondansetron / adverse effects
  • Ondansetron / pharmacology
  • Prospective Studies
  • Young Adult

Substances

  • Antiemetics
  • Delayed-Action Preparations
  • Ondansetron