Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide

Abstract

BACKGROUND The arrhythmogenic potential of short QT intervals has recently been highlighted in patients with a short QT syndrome. Drug-induced QT-interval prolongation is a known risk factor for ventricular tachyarrhythmias. However, reports on drug-induced QT-interval shortening are rare and proarrhythmic effects remain unclear. OBJECTIVE Recently, rufinamide, a new antiepileptic drug for the add-on treatment of Lennox-Gastaut syndrome, was approved in the European Union and the United States. Initial trials showed drug-induced QT-interval shortening. The aim of our study was to evaluate the effects of rufinamide on QT intervals in patients with difficult-to-treat epilepsies. METHODS Nineteen consecutive patients with Lennox-Gastaut syndrome and other epilepsy syndromes were included (n = 12 men; mean age 41 ± 12 years). QRS, QT, and Tpeak-Tend intervals were analyzed before and during rufinamide treatment. RESULTS The mean QT interval shortened significantly following rufinamide administration (QT interval 349 ± 23 ms vs 327 ± 17 ms; corrected QT interval 402 ± 22 ms vs 382 ± 16 ms; P = .002). Tpeak-Tend intervals were 79 ± 17 ms before and 70 ± 20 ms on treatment (P = .07). The mean reduction of the corrected QT interval was 20 ± 18 ms. During follow-up (3.04 ± 1.09 years), no adverse events including symptomatic cardiac arrhythmias or sudden cardiac deaths were observed. CONCLUSION QTc-interval shortening following oral rufinamide administration in a small patient group was not associated with significant clinical adverse effects. These observations nothwithstanding, the ability of rufinamide to significantly shorten the QT interval portends a potential arrhythmogenic risk that may best be guarded against by periodic electrocardiographic recordings.

hERG K+Channels: Structure, Function, and Clinical Significance

“…In a recent study, Schimpf et al (556) reported that the antiepileptic drug rufinamide caused ϳ20 ms shortening of corrected QT interval in a sample of 19 patients. There were, however, no adverse events (cardiac arrhythmias or sudden cardiac arrest) observed in this group over an average 3-yr follow up.…”

Cardiac and Autonomic Mechanisms Contributing to SUDEP

“…It has been associated with mutations in potassium channels genes KCNH2, KCNQ1, and KCNJ2, leading to earlier repolarization, atrial arrhythmias, syncope, and sudden death (Brugada et al, 2004;Hong et al, 2005;Priori et al, 2005). Some antiepileptic medications like rufinamide may promote QTc shortening (Schimpf et al, 2012).…”

Electrocardiographic Effects of a Supratherapeutic Dose of Oritavancin

“…While the extent of decrease was small and would not bring a normal QTc into the range associated with arrhythmias in the short QT syndrome 10 , it does raise the question of risk that might be related to more substantial drug-induced QT shortening. We are not aware of any clearly documented instances of arrhythmias arising from drug-induced QT shortening, and drugs that do substantially reduce QTc are in clinical use 11 . Nevertheless, some investigators recommend caution 12 .…”