By: Jenny Park, PharmD Candidate c/o 2015

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Methadone maintenance therapy is prescribed for opioid dependency. Many HIV patients who were former injection drug abusers rely on methadone maintenance. Although there is limited data, research suggests lamivudine, ritonavir, and zidovudine to be the most common concomitant drugs in methadone associated torsades and prolonged QT interval.¹ Over the past decade, there have been many reports of methadone-associated arrhythmias. An arrhythmia is an irregular heartbeat where the heart may beat too fast, too slow, or even too early.² When electrical impulses that contract the heart are disrupted, arrhythmias can occur. The risk of cardiac events can be correlated with QT prolongation, which is associated with voltage-gated potassium channels. “A QT interval, is the length of time required for the heart to repolarize following the onset of depolarization”.³

According to the U.S. Food and Drug Administration Adverse Event Reporting System, from November 1997 to June 2011, there were 1646 cases of ventricular arrhythmias or cardiac arrest and 379 cases of QT prolongation or torsade de pointes associated with methadone.⁴ Deaths occurred in 42% of these cardiac events and 11% of these fatalities were related to torsade de pointes. ⁴

In an effort to reduce arrhythmia risk, the center for substance abuse (CSAT) issued five specific recommendations.⁵ First, clinicians should inform patients about the risk of arrhythmias when prescribing methadone. Second, clinicians should probe their patients’ medical histories for heart disease, arrhythmia or syncope. Third, patients should be screened for corrected QT (QTc) interval if the methadone dose is greater than 100 mg per day or if patients have unexplained seizures. A corrected QT interval estimates the interval at a heart rate of 60bpm and will allow QT values to be compared at different heart rates. If patients have a QT interval between 450 – 500 milliseconds, the risks and benefits of methadone treatment should be discussed. If the interval is more than 500 milliseconds, the dose should be decreased or discontinued. Lastly, physicians should be aware of drug interactions that prolong the QT interval.⁵

Although research is limited and findings may not be definite, these associated deaths should be something that all prescribers be aware of. The new recommendations should be taken seriously in regards to patients taking methadone concomitantly. Hopefully, with such close monitoring, patients will get the treatment they need with fewer cardiac deaths.

SOURCES:

1. AIDs International Society. Methadone Arrhythmia rising in the US. And ART may pose a higher risk. July 11, 2013. International AIDS society website. <http://www.iasociety.org/Article.aspx?elementId=15315> Accessed November 14, 2013
2. Medical News Today. What is arrhythmia? What causes arrhythmia? Medical news today website. September 9, 2009. Available at <http://www.medicalnewstoday.com/articles/8887.php> Accessed January 18, 2014
3. US Pharmacist. Drug-Induced QT prolongation. US Pharmacist website. February 20, 2007. Available at <http://www.uspharmacist.com/content/d/featured_articles/c/10396/> Accessed October 31, 2013.
4. PubMed. Trends in reporting methadone associated cardiac arrhythmias. 1997-2011; an analysis of registry data. PubMed website. May 21, 2013. Available at <http://www.ncbi.nlm.nih.gov/pubmed/23689766> Accessed October 31, 2013.
5. Medscape. Safety Guidelines Issued for prescribing methadone. Medscape Website. January 27, 2009. Available at < http://www.medscape.org/viewarticle/584826> Accessed October 31, 2013

Published by Rho Chi Post