Methadone Therapy in Underserved Urban Community: QTc Prolongation and Life‐Threatening Ventricular Arrhythmias

Abstract

SUMMARYAims: Methadone has been associated with QTc prolongation and ventricular arrhythmias but the prevalence of QTc prolongation and association with ventricular arrhythmias remains unclear. We investigated this in our inner city urban community (Bronx, New York) that has a large number of patients on methadone. Methods: Telemetry records, nursing documentation and electronic charts of 291 patients spanning856 encounters were evaluated. QT was manually measured from ECG utilizing standardized QT measurement guidelines and was corrected for heart rate using Hodges formula. QTc >470 ms in males and >480 ms in females was considered to be prolonged. Results: Patients had prolonged QTc, QTc >500 ms and ventricular arrhythmias during 25.6%, 14.1% and 3.4% of encounters, respectively. There was a very weak dose dependent relationship between methadone dose and QTc (Spearman's rho = 0.09).In addition to methadone, patients were on at least one QT prolonging drugs during 39% of the encounters. Patients who were receiving two interacting drugs in addition to methadone had the highest prevalence (29%) of QTc prolongation. Conclusion: Although the prevalence of QTc prolongation among patients on methadone therapy is high, the prevalence of ventricular arrhythmia is relatively low. Hospitalized patients on sustained methadone therapy are frequently on multiple additional QTc prolonging drugs. There is no significant dose dependent relationship between methadone dose and QTc. However, the concurrent use of methadone and interacting drugs lead to an increased prevalence of QTc prolongation.

Opioids and Cardiac Arrhythmia: A Literature Review

“…Despite findings supporting the presence of a relation between methadone dose and QT interval prolongation, the evidence of some studies has not confirmed this. Recently Chowdhury et al [66] reported a high prevalence of prolongation of QT interval in 291 patients on methadone, but the relationship between methadone dose and QTc was weak and not significant. Also they observed that the prevalence of ventricular arrhythmia was low in these patients [66].…”

“…Recently Chowdhury et al [66] reported a high prevalence of prolongation of QT interval in 291 patients on methadone, but the relationship between methadone dose and QTc was weak and not significant. Also they observed that the prevalence of ventricular arrhythmia was low in these patients [66]. Two separate studies also failed to find an association between methadone dose and QTc interval; however, Roy et al [67] concluded that even low doses of methadone can produce significant prolonged QT interval, while Stallvik et al [36] suggested that even modest doses of methadone (less than 100 mg/day) have no correlation with clinically significant QTc prolongation [36,67].…”

Integrating in vitro data and physiologically based kinetic modeling-facilitated reverse dosimetry to predict human cardiotoxicity of methadone

“…The curves represent the prediction based on a f u,p of 0.22 (black line), 0.15 (red line), 0.055 (blue line) and 0.034 (green line). Symbols represent the data obtained from case reports, case series of individuals (orange triangles) (Esses et al 2008 ; Fredheim et al 2006 ; Krantz et al 2002 ) and other studies as follows: Bart et al ( 2017 ) (purple circle); Carlquist et al ( 2015 ) (orange square); Chang et al ( 2012 ) (green circle) Chowdhury et al ( 2015 ); (dark blue cross); Cruciani et al ( 2005 ) (green cross) Eap et al ( 2007 ); (green star); Ehret et al ( 2006 ) (dark blue triangle) Fareed et al ( 2013 ); (dark blue circle) Heesch et al ( 2015 ); (dark blue star) Krantz et al ( 2005 ); (orange circles) Maremmani et al ( 2005 ); (green square); Martell et al ( 2005 ) (green triangle) Peles et al ( 2007 ); (orange star); Reddy et al ( 2010 ) (orange circles) Roy et al ( 2012 ); (dark blue square). The in vivo data are summarized in Table S1 and S2 (color figure online) …”

The Risk of Ventricular Dysrhythmia or Sudden Death in Patients Receiving Serotonin Reuptake Inhibitors With Methadone: A Population-Based Study

“…Methadone is a long-acting opioid used primarily as treatment for opioid use disorder ( Bell and Strang, 2020 ). However, methadone maintenance therapy can be complicated by QT interval prolongation in up to 50% of patients ( Fanoe et al, 2007 ; Anchersen et al, 2009 ; Fareed et al, 2013 ; Chowdhury et al, 2015 ; Titus-Lay et al, 2021 ), with case reports and pharmacovigilance data describing the potential for ensuing Torsade de Pointes and sudden cardiac death ( Chugh et al, 2008 ; Stringer et al, 2009 ; Kao et al, 2013 ; Kao et al, 2015 ). Risk factors for QT interval prolongation and sudden cardiac death are well described, and include older age, female sex, electrolyte abnormalities, and underlying heart disease ( Chugh, 2010 ; Tisdale et al, 2013 ; Trinkley et al, 2013 ).…”