Evaluation of Methadone-Induced QTc Prolongation in a Veteran Population

This study and the study by Fareed and colleagues are similar in that both are retrospective, compare baseline QTc intervals and QTc intervals while using methadone, and include subjects of a similar age and gender. However, the subjects in the Fareed and colleagues study were using methadone for maintenance treatment at higher doses than in the present study. Additionally, the results of the studies differ. Fareed and colleagues found a prolongation of the QTc interval with methadone use. Although the present study has many limitations, it adds additional information to the medical literature regarding the QTc interval of veterans using methadone in lower doses at an average of 29 mg/d.

Conclusion

In this study of veterans using methadone for pain, methadone did not significantly increase the QTc interval. Two patients had a prolonged QTc interval of ≥ 500 msec while taking methadone. The QTc interval did not vary by methadone daily dose, and the concurrent use of QTc prolonging medications together with methadone did not increase the QTc interval. The concurrent use of strong CYP3A4 inhibitors could not be assessed, because none of the patients were on these medications.

Despite these findings, the study had several limitations, and there is a black box warning included in the labeling of methadone regarding QTc interval prolongation, TdP, and death. Therefore, it is advisable to monitor the QTc interval in patients using methadone, even at low doses. In those patients with a prolonged QTc interval and/or risk factors for QTc prolongation, methadone should either be avoided or used cautiously with close monitoring of the QTc interval.

Acknowledgments
This manuscript was prepared and research was conducted with resources and the use of facilities at the Southern Arizona VA Health Care System in Tucson, Arizona.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
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