Assessment of drug‐induced proarrhythmias due to pilsicainide in patients with atrial tachyarrhythmias

Abstract

BackgroundPilsicainide, a pure Na+ channel blocker, is a popular antiarrhythmic drug for the management of atrial tachyarrhythmias (AT), in Japan. However, serious drug-induced proarrhythmias (DIPs) may unexpectedly occur. We assessed the clinical background of AT patients presenting with DIPs caused by pilsicainide.MethodsThis study retrospectively enrolled 874 consecutive patients (543 men, 63.6±15.3 years old, and 57.9±16.5 kg of body weight), who were orally administered pilsicainide for AT management. We evaluated the relationship between DIPs and serum pilsicainide concentration, renal dysfunction (estimate glomerular filtration rate, eGFR), and electrocardiogram (ECG) parameters.ResultsAmong the patients, 154 (17.6%) had renal dysfunction (eGFR<50 mL/min), including 12 (1.4%) on hemodialysis. DIPs were present in 10 patients (1.1%): all had renal dysfunction, and one was on hemodialysis. The eGFR in DIP patients was significantly lower than that in the non-DIP patients (32.2±15.1 vs. 68.4±22.1 mL/min, p<0.001). Among the clinical factors measured, only renal dysfunction (eGFR<50 mL/min) was significantly associated with DIPs (OR 44.6; 95% CI 5.61–335.0, p<0.001). Interestingly, among the ECG parameters, the corrected QT (QTc) intervals in DIP patients were longer than those in non-DIP patients (555.8±37.6 vs. 430.7±32.6 ms, p<0.001). As pilsicainide concentration increased, both QRS and QTc intervals prolonged. The latter were improved by discontinuing pilsicainide administration, and additional treatments.ConclusionsDIPs caused by pilsicainide administration were strongly associated with renal dysfunction. Hence, confirmation of renal function would be necessary prior to and/or during the pilsicainide administration.

Pilsicainide Toxicity-Induced Brugada-Like ST Segment Elevation and Increased Pacing Voltage Threshold

“…Since pilsicainide is primarily excreted by the kidneys, its duration of action is prolonged in patients with renal dysfunction [4]. Druginduced arrhythmias caused by pilsicainide are strongly associated with renal dysfunction [9]. Although our patient was elderly and had chronic kidney disease, she was prescribed a typical dose of pilsicainide.…”

Case report: An autopsy case of pilsicainide poisoning

“…Pilsicainide is recognized as a safe drug, but shows pro-arrhythmic effects in cases of intoxication. Serum pilsicainide levels have been reported to show a significant positive correlation with the electrocardiographic findings of PQ, QRS, and ST intervals and QTc prolongation ( Horita et al, 2004 ; Koike et al, 2016 ). Pilsicainide induces tachyarrhythmias such as ventricular tachycardia, as a result of QTc and QRS prolongation ( Horita et al, 2004 ; Kaneko et al, 2012 ), and bradyarrhythmias such as sinus pause and atrioventricular block ( Toeda et al, 2000 ).…”

Successful treatment for various arrhythmias in an older patient treated with pilsicainide for paroxysmal supraventricular tachycardia

“…Drug-induced proarrhythmia caused by pilsicainide administration is strongly associated with renal dysfunction, because it is largely excreted through the kidneys. [1][2][3][4] Thus, careful attention to the dose of anti-arrhythmic agents especially excreted by kidney is important for older patients.…”