Torsades de pointes with methadone

(1) Methadone is an opiate used for replacement therapy of opiate addiction that causes dose-dependent QT prolongation. (2) Severe ventricular arrhythmias such as torsades de pointes have been reported, usually in patients on high doses (100 mg to 400 mg/day). (3) Methadone has a long plasma elimination half-life, and this poses a risk of accumulation. Accumulation is especially problematic when the dose is increased too rapidly. Combining methadone with a CYP 3A4 inhibitor increases the risk of torsades de pointes, as methadone is metabolised by this enzyme system. (4) Factors potentially predisposing patients to torsades de pointes must be analysed in each case; these include preexisting bradycardia, congenital QT prolongation, hypokalemia, and concomitant use of other drugs inducing QT prolongation. (5) This adverse effect has also been reported with levacetylmethadol (another opiate) and with heroin. It does not seem to occur with buprenorphine.