QT interval prolongation: prevalence, risk factors and pharmacovigilance data among methadone-treated patients in France

Abstract

Several reports have suggested the role of methadone in QT prolongation, Torsades de Pointes (TdP), and ventricular arrhythmia. The aim of this study was to identify the frequency of QT interval prolongation and QT dispersion among a population of addict patients treated with methadone, completed by the description of cardiac events reported to the French pharmacovigilance system. QT interval (corrected with the Bazett's method) and dispersion were measured on a cohort of patients treated with methadone during their visit to addiction specialized centers in Southwest of France. Whenever possible, methadone blood concentrations were measured. In addition, reports concerning methadone were searched in the French Pharmacovigilance database from 1996 to 2007. The cohort included 42 patients with mean QTc length of 414.3 ± 28.5 ms and mean QT dispersion of 66.0 ± 41.1 ms. None of the patient presented a QTc above 500 ms. These values were higher in patients with recent increase in methadone dose, use of tobacco or drugs prolonging QT, and history of cardiac disease. We found five cases of QT prolongation (3 TdP) and seven cases of sudden deaths in the French pharmacovigilance database (2.2% of methadone reports). Most of these events occurred after introducing methadone or another drug potentially interacting with methadone. Methadone can prolong the QT interval at dose usually used for addiction maintenance treatment in France. A cardiac evaluation, with at least a systematic ECG, could be useful during methadone treatment, particularly in case of recent modification of the regimen.