Effects of Buprenorphine on Cardiac Repolarization in a Patient with Methadone-Related Torsade de Pointes

Abstract

Torsade de pointes is a rare but potentially fatal ventricular arrhythmia that is often triggered by drugs that prolong the rate-corrected QT (QTc) interval. This arrhythmia has been attributed to levacetylmethadol and methadone, synthetic opioids used to treat heroin addiction. Levacetylmethadol, a derivative of methadone, is being withdrawn from the United States market because its use waned after a black box warning was issued to require electrocardiographic monitoring. Therefore, methadone and buprenorphine are the only opioids available for the treatment of heroin addiction. To our knowledge, the cardiac safety of buprenorphine in patients with methadone-related QTc prolongation has not been described. We report a patient who developed torsade de pointes while receiving high-dose methadone and was successfully inducted onto buprenorphine under close medical supervision. No clinically important QTc prolongation was observed in the acute setting or during follow-up. This observation suggests that buprenorphine may be a safe alternative to oral methadone in patients with opioid addiction who develop torsade de pointes.

Role of antiretroviral treatment in prolonging QTc interval in HIV-positive patients

“…6,7,20e22 In the recent retrospective study conducted by Ehret et al 23 among 167 methadone maintenance patients, the prevalence of QTc prolongation was 16.2% compared to 0% in 80 control subjects, and was associated with the daily dose of methadone. This finding suggests that, in the case of methadone-related QTc prolongation or torsade de pointes, one option could be the substitution of methadone with buprenorphine, as recently proposed by Krantz et al 24,25 Regarding the effect of antiretroviral agents on QTc interval, to date there is only one report on efavirenzassociated QTc prolongation and torsade de pointes. 11 A previously unrecognised association between QTc interval prolongation or torsade de pointes and protease inhibitors (lopinavir, nelfinavir, ritonavir, and saquinavir) has recently been described due to a dose-dependent block of human ether-a-go-go related gene potassium channels.…”

Suboxone® (Buprenorphine/Naloxone) as an Agonist Opioid Treatment in Spain: A Budgetary Impact Analysis

“…Similarly, in a large cross-sectional study, 28% male and 32% female heroin addicts on MM treatment had prolonged QTc interval, whilst none of the subjects treated with buprenorphine had QTc interval 1 440 ms [40] . Of note is the report of the safe and successful induction onto buprenorphine of a patient who developed TdP while receiving high-dose methadone [45] .…”

Management of opioid use disorders: a national clinical practice guideline

“…47 Case series have reported that transitioning patients taking methadone who were experiencing torsades de pointes to buprenorphine corrected the condition. 48,49 Long-term opioid use, including opioid agonist treatment, may lead to abnormalities in the endocrine system, mainly affecting the gonadal axis and leading to hypogonadism. 50,51 A meta-analysis including four studies showed that methadone was associated with a significantly higher frequency of male sexual dysfunction than buprenorphine-naloxone.…”