Evaluation of the acute effect of palonosetron on transmural dispersion of myocardial repolarization

Background: 5-hydroxytryptamine receptor type-3 (5-HT3) antagonists are widely used for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) and regarded to have a high safety profile. However, several electrocardiographic changes and cardiac arrhythmias have been reported due to administration of 5-HT3 antagonists. Only prolongation of QT interval has been investigated as an index of potential for life-threatening arrhythmias in adult patients using 5-HT3 antagonists. Recently, increase in transmural dispersion of repolarization (TDR) has been proposed as a more reliable determinant of arrhythmogenic potential.

Aim: To assess the effects of palonosetron, a second-generation 5-HT3 antagonist, on the T-wave peak to T-wave end (TpTe) interval which has been proposed as a reliable index of spatial TDR.

Patients and methods: A total of 50 consecutive Cancer patients (aged: 57 +/- 12 years) who were scheduled to receive emetogenic chemotherapy were included to the study. Baseline12-lead electrocardiography (ECG) recordings were obtained. Then, all patients received 8 mg intravenous dexamethasone followed by a single dose of 0.25 mg intravenous palonosetron administered over 30 seconds. A second ECG was performed 30 minutes after the administration of palonosetron. Indices of cardiac repolarization and TDR before and after the administration of palonosetron were compared.

Results: In comparison with baseline there was no statistically significant change in any of the heart rate-corrected parameters, including QT(c) (lead V5), QT(maxc), QT(minc), QT(cd), TpTe (V5), TpTe(max), TpTe(min), TpTe(d) and TpTe/QT (V5).

Conclusions: Palonosetron does not have any significant effect on QT(c) and TpTe intervals. It might be the drug of choice for prophylaxis of CINV in Cancer patients receiving chemotherapy with known cardiotoxic potential or who have pre-existing cardiac disease that predispose them to drug-induced arrhythmias.