Single-Blind Study of the Effects of Intravenous Dolasetron Mesylate Versus Ondansetron on Electrocardiographic Parameters in Normal Volunteers

Abstract

A single-blind, randomized, five-way cross-over, safety and tolerability trial was conducted to determine whether intravenous (i.v.) dolasetron mesylate at varying single doses induces changes in ECG intervals in healthy volunteers and to compare these changes with a single intravenous dose of ondansetron or placebo. Thirty healthy male volunteers received 1.2, 1.8, and 2.4 mg/kg i.v. dolasetron mesylate, 32 mg i.v. ondansetron, and placebo on 5 separate days. ECGs were recorded at intervals during the 24 h after study drug administration. The changes in ECG intervals observed after dolasetron mesylate or ondansetron were acute, transient, and asymptomatic. Dolasetron mesylate resulted in slight but statistically significant dose-related increases in heart rate (HR) and PR and QRS intervals (between h 0 and 4). A statistically significant increase in QTc interval was detected with both dolasetron mesylate (2.4 mg/kg) and ondansetron. Ondansetron also produced a slight but statistically significant increase in JT interval and a decrease in HR. These changes in ECG intervals were usually observed between h 0 and 4; all parameters returned to baseline within 8 h of treatment. The results demonstrate that both dolasetron mesylate and ondansetron prolong the QTc interval. However, dolasetron mesylate predominantly altered ECG parameters indicative of ventricular depolarization (QRS duration), whereas ondansetron predominantly affected ventricular repolarization as measured by a prolongation in the JT interval. Both dolasetron and ondansetron were well tolerated. The adverse event (AE) rate was 13.3% (4 of 30); all AE were of mild or moderate severity and were distributed across all dose arms.

Palonosetron versus ondansetron for prevention of chemotherapy-induced nausea and vomiting in paediatric patients with cancer receiving moderately or highly emetogenic chemotherapy: a randomised, phase 3, double-blind, double-dummy, non-inferiority study

“…13,[16][17][18][19][20] Palonosetron also appears to have an advantageous safety profile compared with ondansetron, granisetron, dolasetron, and tropisetron, which have been associated with electrocardiographic changes and arrhythmias, sometimes leading to the potentially fatal heart rhythm torsades de pointes. 13,14,[21][22][23][24] Palonosetron has been shown not to cause arrhythmias or symptomatic electrocardiographic changes. [25][26][27] The present study was designed to assess the efficacy and safety of two intravenous doses of palonosetron (10 and 20 µg/kg) in paediatric patients with cancer aged from new-born (full term; ≥37 weeks) to <17 years, scheduled to undergo moderately or highly emetogenic chemotherapy.…”

Ventricular tachycardia after ondansetron administration in a child with undiagnosed long QT syndrome

“…12 Paradoxically, subsequent to the FDA warning on droperidol, ondansetron became adopted as a widely accepted, albeit far more costly substitute, despite the fact that it was also known to prolong the QT interval. 13,14 More recently, ondansetron and droperidol have been shown to have almost identical effects on the QT intervals of patients being treated for PONV in the recovery room. 3 The mechanism by which ondansetron prolongs QT is via blockade of the human ether-a-go-go-related gene (HERG) potassium channel in the myocardium, leading to disruption of the rapid delayed rectifier potassium current (I kr ).…”

Deletion of the Serotonin Receptor Type 3A in Mice Leads to Sudden Cardiac Death During Pregnancy

“…Htr3 antagonists, which are widely used as antiemetics, have been reported to prolong the QT intervals and to be related to tosades de pointes in high concentrations. [9][10][11][12] This finding suggests that serotonin and Htr3 might be related to cardiac repolarization. Recently, it was reported that mouse cardiac tissue contained mRNA for Htr3.…”