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Medications That Prolong the QT IntervalMedications That Prolong the QT Interval

JAMA. 2003;290(8):1025-1025. doi:10.1001/jama.290.8.1025-a
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AUTHOR INFORMATION

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

MEDICATIONS THAT PROLONG THE QT INTERVAL

To the Editor: In their article about the QT interval, Dr Al-Khatib and colleagues1 described the propensity of a number of drugs for causing QT prolongation. The authors categorized the synthetic opioid methadone as an "improbable" agent regarding its potential to delay repolarization. Their review, however, was based on an expert panel discussion from August 2000. Since that time, a number of new findings have emerged that, taken together, suggest that an association between methadone and QT prolongation can no longer be considered "improbable."

Recently, a series of 17 methadone-treated patients experiencing torsade de pointes was described.2 Subsequently, in an experimental model methadone was found to inhibit the delayed rectifier potassium ion current (IKr), a plausible mechanism for arrhythmia.3 In this model, methadone was 100 times more potent an inhibitor of IKr than morphine, a naturally occurring opioid. Preliminary electrocardiographic (ECG) data suggested that methadone induction can increase the corrected QT interval (QTc) by nearly 8%,4 exceeding generally accepted thresholds for clinical importance. In a larger prospective study, a statistically significant increase of 10.6 ms in QTc was identified 2 months following methadone induction, although the clinical significance of this finding is uncertain.5

Although we believe that routine ECG screening is probably unwarranted in the majority of patients, further ECG and genetic analyses may define characteristics of high-risk patients in whom screening may be beneficial.

References
Al-Khatib SM, Allen LaPointe NM, Kramer JM, Califf RM. What clinicians should know about the QT interval.  JAMA.2003;289:2120-2127.
Krantz MJ, Lewkowiez L, Hays H.  et al.  Torsade de pointes associated with very-high dose methadone.  Ann Intern Med.2002;137:501-504.
Katchman AN, McGroary KA, Kilborn MJ.  et al.  Influence of opioid agonists on cardiac human ether-a-go-go-related gene K(+) currents.  J Pharmacol Exp Ther.2002;303:688-694.
Huber A, Ling W, Fradis J.  et al.  Comparison of the effects of methadone and LAAM on the electrocardiogram [abstract].  Drug Alcohol Depend.2001;63:S70.
Martell BA, Arnsten JH, Ray B, Gourevitch MN. The impact of methadone induction on cardiac conduction in opiate users.  Ann Intern Med.2003;139:154-155.

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Al-Khatib SM, Allen LaPointe NM, Kramer JM, Califf RM. What clinicians should know about the QT interval.  JAMA.2003;289:2120-2127.
Krantz MJ, Lewkowiez L, Hays H.  et al.  Torsade de pointes associated with very-high dose methadone.  Ann Intern Med.2002;137:501-504.
Katchman AN, McGroary KA, Kilborn MJ.  et al.  Influence of opioid agonists on cardiac human ether-a-go-go-related gene K(+) currents.  J Pharmacol Exp Ther.2002;303:688-694.
Huber A, Ling W, Fradis J.  et al.  Comparison of the effects of methadone and LAAM on the electrocardiogram [abstract].  Drug Alcohol Depend.2001;63:S70.
Martell BA, Arnsten JH, Ray B, Gourevitch MN. The impact of methadone induction on cardiac conduction in opiate users.  Ann Intern Med.2003;139:154-155.
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