Methadone‐associated Torsades de Pointes (polymorphic ventricular tachycardia) in opioid‐dependent patients

Abstract

We wish to raise the level of awareness of risk factors for TdP among physicians in heroin-treatment clinics who frequently prescribe methadone.

Methadone Safety: A Clinical Practice Guideline From the American Pain Society and College on Problems of Drug Dependence, in Collaboration With the Heart Rhythm Society

“…98 Although data are limited, studies of methadone-associated torsades de pointes similarly indicate that a high proportion of patients had identifiable risk factors. 47,58,77,99 For persons not known to be at a higher risk of QTc interval prolongation, the panel found insufficient evidence to routinely recommend ECG screening. 72 Lintzeris et al, 65 and Gourevitch et al 40 However, given that QTc interval prolongation without arrhythmia is asymptomatic and may not be associated with recognized risk factors, the panel suggests that clinicians consider obtaining an ECG prior to initiation of methadone in all patients.…”

“…4,6,28,29,42,56,102 A QTc interval of 450 to 500 ms in adults is also associated with increased risk of torsades de pointes. 47,57,77 Data from general populations of U.S. adults indicate that less than 5% of men and women have QTc intervals of >450 ms. 83,111 Although the risk associated with a QTc interval of 450 to 500 ms is lower than in patients with QTc intervals of >500 ms, the panel recommends that clinicians consider alternatives to methadone because there may be some additional risk. Factors to consider when deciding whether to initiate methadone include the degree of QTc interval prolongation (intervals close to 450 ms are associated with less risk than intervals closer to 500 ms) and whether there may be reversible risk factors.…”

“…Therefore, for pragmatic purposes, the panel recommends that clinicians utilize the same QTc interval parameters for men and women. Risk factors for QTc interval prolongation include 22,26,31,47,93,96 electrolyte abnormalities such as hypokalemia or hypomagnesemia; impaired liver function; structural heart disease (such as congenital heart defects or a history of endocarditis or heart failure); genetic predisposition such as congenital prolonged QT syndrome or familial history of prolonged QT syndrome; and use of drugs with QTc-prolonging properties (Table 1). Methadone use appears to be associated with risk of prolongation of the QTc interval, 26,55,59,66,69,89 presumably because of its potent inhibitory effects on the human ether a go-go-related gene (hERG) cardiac channel, 52,95 and case reports describe torsades de pointes in patients prescribed methadone.…”

“…Methadone use appears to be associated with risk of prolongation of the QTc interval, 26,55,59,66,69,89 presumably because of its potent inhibitory effects on the human ether a go-go-related gene (hERG) cardiac channel, 52,95 and case reports describe torsades de pointes in patients prescribed methadone. 47,57,77 Other medications associated with QTc interval prolongation and torsades de pointes include various antiarrhythmics, antipsychotics, citalopram, tricyclic antidepressants, fluoroquinolones, and cisapride. 106 The estimated risk of torsades de pointes varies widely, ranging from approximately .001% for cisapride to approximately 8% for quinidine.…”

Pharmacotherapy of Opioid Addiction: “Putting a Real Face on a False Demon”

“…One study associated doses >60 mg in 98 % of patients with QT prolongation [18]. The risk for QT prolongation and subsequent TdP during methadone maintenance is not simply a high-dose phenomenon.…”