title: Trends in reporting methadone-associated cardiac arrhythmia, 1997-2011: an analysis of registry data.
abstract: BACKGROUND
  Long-acting opioids are a leading cause of accidental death in the United States, and methadone is associated with greater mortality rates. Whether this increase is related to the proarrhythmic properties of methadone is unclear.
  
  
  OBJECTIVE
  To describe methadone-associated arrhythmia events reported in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).
  
  
  METHODS
  Description of national adverse event registry data before and after publication of a 2002 report describing an association between methadone and arrhythmia.
  
  
  METHODS
  FAERS, November 1997 and June 2011.
  
  
  METHODS
  Adults with QTc prolongation or torsade de pointes and ventricular arrhythmia or cardiac arrest.
  
  
  METHODS
  FAERS reports before and after the 2002 report.
  
  
  RESULTS
  1646 cases of ventricular arrhythmia or cardiac arrest and 379 cases of QTc prolongation or torsade de pointes were associated with methadone. Monthly reports of QTc prolongation or torsade de pointes increased from a mean of 0.3 (95% CI, 0.1 to 0.5) before the 2002 publication to a mean of 3.5 (CI, 2.5 to 4.8) after it. After 2000, methadone was the second-most common primary suspect in cases of QTc prolongation or torsade de pointes after dofetilide (a known proarrhythmic drug) and was associated with disproportionate reporting similar to that of antiarrhythmic agents known to promote torsade de pointes. Antiretroviral drugs for HIV were the most common coadministered drugs.
  
  
  CONCLUSIONS
  Reports to FAERs are voluntary and selective, and incidence rates cannot be determined from spontaneously reported data.
  
  
  CONCLUSIONS
  Since 2002, reports to FAERS of methadone-associated arrhythmia have increased substantially and are disproportionately represented relative to other events with the drug. Coadministration of methadone with antiretrovirals in patients with HIV may pose particular risk.
  
  
  BACKGROUND
  Colorado Clinical and Translational Sciences Institute, National Institutes of Health, and Agency for Healthcare Research and Quality.
authors.affiliation: Division of Cardiology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kao
authors.forename: Becki
authors.initials: B
authors.lastname: Bucher Bartelson
authors.forename: Vaishali
authors.initials: V
authors.lastname: Khatri
authors.forename: Richard
authors.initials: R
authors.lastname: Dart
authors.forename: Philip S
authors.initials: PS
authors.lastname: Mehler
authors.forename: David
authors.initials: D
authors.lastname: Katz
authors.forename: Mori J
authors.initials: MJ
authors.lastname: Krantz
mesh_terms: D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy; D006323:Heart Arrest / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000453:epidemiology; D008691:Methadone / Q000009:adverse effects*; D012042:Registries; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
chemical_list: D044966:Anti-Retroviral Agents; D008691:Methadone