1156 POSTER High dose palonosetron does not alter ECG parameters including QTc interval in healthy subjects: results of a dose-response, double blind, randomized, parallel E14 study of palonosetron vs. moxifloxacin or placebo

A phase III open-label study to assess safety and efficacy of palonosetron for preventing chemotherapy-induced nausea and vomiting (CINV) in repeated cycles of emetogenic chemotherapy

“…The incidence of QTc prolongation was higher in those patients receiving AC/EC than in those receiving cisplatin; however, the proportion of patients with an increase in QTc (more than 500 ms as an absolute value or more than 60 ms difference from the baseline value) was very low, both in the patients receiving cisplatin and those receiving AC/EC. Therefore, the influence of palonosetron on QTc interval was not found to be clinically significant, as reported in previous studies [8,16].…”

“…Interactions of some 5-HT 3 receptor antagonists with human cardiac ion channels are known and have been reported [15], and recently, the effect of palonosetron on QTc prolongation has been studied in an European doubleblind, randomized, placebo-controlled trial, which showed no significant effect on any ECG interval, including QTc duration, with intravenous palonosetron administered up to 2.25 mg, three times the study dose [16]. In the doubleblind, randomized phase III study, the incidences of QTc prolongation in the palonosetron group and in the granisetron group were comparable [8].…”

Palonosetron for the treatment of chemotherapy-induced nausea and vomiting

“…A clinical study in male and female volunteers showed that the cardiac profile of palonosetron is the same as placebo. There were no electrocardiographic or dose response effects, including QTc prolongation, of palonosetron up to a 2.25 mg IV dose, a ninefold safety margin [64].…”

Palonosetron versus older 5-HT3 receptor antagonists for nausea prevention in patients receiving chemotherapy: a multistudy analysis

“…With respect to laboratory values, vital signs, and ECG findings, there were no pronounced differences between palonosetron and older 5-HT 3 RAs. The studies analyzed here did not thoroughly evaluate QTc measures; however, recent studies in patients with cancer 17,18 and a thorough QTc study in healthy subjects that used a positive control (ie, moxifloxacin) 16 demonstrated no significant QTc changes associated with palonosetron. This is in contrast to evidence of significant dose-related QTc prolongation with ondansetron, which led to the removal of the 32-mg single dose from its label, 30 and an increased risk of cardiac arrhythmias with IV dolasetron, which is no longer recommended.…”