High dose methadone and ventricular arrhythmias: a report of three cases.

Three patients who developed torsades de pointes while receiving high dosages of oral methadone (>600mg/day) are presented. In all of the cases, drug interactions involving methadone and CYP3A4 isoenzyme system were possible. Two cases involve some previous cardiac impairment. The potential for toxic doses of methadone to cause ventricular arrhythmia is raised by these cases. Until further evidence is available it may be prudent to be vigilant for arrhythmias when high dosages of methadone (>600mg/day) are used, especially in patients on other drugs that interact with the CYP3A4 isoenzyme system, or with conditions that predispose to torsades de pointes.