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Torsade de Pointes Associated with Very-High-Dose Methadone

Mori J. Krantz, MD; Laurent Lewkowiez, MD; Helen Hays, MD; Mary Ann Woodroffe, BScN; Alastair D. Robertson, PhD; and Philip S. Mehler, MD

17 September 2002 | Volume 137 Issue 6 | Pages 501-504

Background: Methadone is an effective treatment for opioid dependency and chronic pain. A methadone derivative, levacetylmethadol, was withdrawn from the European market after being associated with torsade de pointes. To date, no association between methadone and this arrhythmia has been described.

Objective: To evaluate a series of methadone-treated patients experiencing torsade de pointes.

Design: Retrospective case series.

Setting: Methadone maintenance treatment programs in the United States and a pain management center in Canada.

Patients: 17 methadone-treated patients who developed torsade de pointes.

Measurements: Chart review for concomitant arrhythmia risk factors and quantification of corrected QT interval (QTc).

Results: The mean daily methadone dose was 397 ± 283 mg, and the mean QTc interval was 615 ± 77 msec. Fourteen patients had a predisposing risk factor for arrhythmia. A cardiac defibrillator or pacemaker was placed in 14 patients; all 17 patients survived.

Conclusions: This series raises concern that very-high-dose methadone may be associated with torsade de pointes. Given the likely expansion of methadone treatment into primary care, further investigation of these findings is warranted.

Editors' Notes Context Several drugs, including antiarrhythmic agents, antihistamines, and tricyclic antidepressants, can cause acquired long-QT syndrome (torsades de pointes). Contribution This case series describes 17 patients who had torsades de pointes while taking very high doses of methadone for chronic pain or methadone maintenance. The average daily methadone dose was about 400 mg. Fourteen of the patients had known risk factors for arrhythmia, such as hypokalemia, or were taking other drugs that could prolong the QT interval. Cautions These data suggest, but do not prove, that very-high-dose methadone can cause torsades de pointes. –The Editors

 

Author and Article Information

From Denver Health Medical Center and The University of Colorado Health Sciences Center, Denver, Colorado; University of Alberta, Edmonton, Alberta, Canada.

Acknowledgments: The authors thank Lisa Kosmiski, Fred Masoudi, William Baker, and Edward Havranek for manuscript review and Megan Marx, DeeAnn Rivera, and Jon Lee for assistance with data collection.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Mori J. Krantz, MD, Division of Cardiology, Denver Health Medical Center, Mail Code 0960, 777 Bannock Street, Denver, CO 80204-4507.

Current Author Addresses: Drs. Krantz and Lewkowiez: Denver Health Medical Center, 777 Bannock Street, Mailcode 0960, Denver, CO 80204.

Dr. Hays and Ms. Woodroffe: 210 Meadowlark Place Professional Centre, 8708 155 Street, Edmonton, Alberta T5R 1W2, Canada.

Dr. Robertson: University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Box B-130, Denver, CO 80262.

Dr. Mehler: Denver Health Medical Center, 660 Bannock Street, Mailcode 1914, Denver, CO 80204.

Author Contributions: Conception and design: M.J. Krantz, L. Lewkowiez, H. Hays, M.A. Woodroffe, P.S. Mehler.

Analysis and interpretation of the data: M.J. Krantz, L. Lewkowiez, H. Hays, M.A. Woodroffe, A.D. Robertson, P.S. Mehler.

Drafting of the article: M.J. Krantz, L. Lewkowiez, H. Hays, M.A. Woodroffe, A.D. Robertson, P.S. Mehler.

Critical revision of the article for important intellectual content: M.J. Krantz, L. Lewkowiez, H. Hays, M.A. Woodroffe, A.D. Robertson, P.S. Mehler.

Final approval of the article: M.J. Krantz, L. Lewkowiez, H. Hays, M.A. Woodroffe, A.D. Robertson, P.S. Mehler.

Provision of study materials or patients: M.J. Krantz, H. Hays, M.A. Woodroffe.

Statistical expertise: M.J. Krantz, A.D. Robertson.

Administrative, technical, or logistic support: M.J. Krantz, P.S. Mehler.

Collection and assembly of data: M.J. Krantz, P.S. Mehler.

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Summaries for Patients
Very High Doses of Methadone May Cause Abnormal Heart Rhythm

Annals 2002 137: I-42. [Full Text]  

Letters
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Annals 2003 139: 154-155. [Full Text]  

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