Does Subutex (buprenorphine) increase the QT interval?

From the Guidelines

Subutex (buprenorphine) generally does not significantly increase the QT interval at therapeutic doses, making it a safer option for patients with risk factors for QT prolongation or those with existing cardiac conditions, as supported by the most recent and highest quality study 1. When considering the use of Subutex, it's essential to weigh the benefits against potential risks, particularly in patients with pre-existing heart conditions or those taking other medications that may prolong the QT interval.

• The study published in the European Heart Journal in 2014 1 highlights the differences in QT interval prolongation between methadone and buprenorphine, with buprenorphine causing far less prolongation.
• A more recent study published in the Mayo Clinic Proceedings in 2021 1 emphasizes the importance of individualizing treatment with buprenorphine, considering factors such as daily dose, indication for treatment, and risk of relapse.
• Another study published in the European Heart Journal in 2006 1 provides guidelines for managing patients with ventricular arrhythmias and preventing sudden cardiac death, including recommendations for removing offending agents that may cause QT prolongation. However, it's crucial to note that buprenorphine may have minor effects on the QT interval at very high doses, and concomitant use with other QT-prolonging medications may lead to a cumulative effect.
• Patients with risk factors, such as pre-existing heart conditions, electrolyte abnormalities, or liver disease, may require closer monitoring and more cautious management. Overall, the available evidence suggests that Subutex is a relatively safe option for patients with opioid use disorder, particularly when compared to methadone, but careful consideration of individual patient factors and potential interactions is necessary to minimize risks.

From the FDA Drug Label

QTc Prolongation Thorough QT studies with buprenorphine products have demonstrated QT prolongation ≤ 15 msec. This QTc prolongation effect does not appear to be mediated by hERG channels Based on these two findings, buprenorphine is unlikely to be pro‐arrhythmic when used alone in patients without risk factors.

Buprenorphine may increase the QT interval, but the effect is small (≤ 15 msec) and is unlikely to be pro-arrhythmic in patients without risk factors 2.

From the Research

QT Interval Prolongation and Buprenorphine

• Buprenorphine, also known as Subutex, does not appear to increase the QT interval, according to several studies 3, 4, 5, 6, 7.
• A study published in the Journal of Drug and Alcohol Dependence found that buprenorphine did not prolong the QT interval in patients treated with the medication 3.
• Another study published in the journal Pharmacotherapy reported a case of a patient who developed torsade de pointes while receiving high-dose methadone, but did not experience QT interval prolongation after being switched to buprenorphine 4.
• A study published in the British Journal of Clinical Pharmacology found that buprenorphine did not prolong the QT interval in patients treated with the medication, whereas methadone was associated with QT interval prolongation 5.
• A case report published in the Netherlands Heart Journal found that buprenorphine was a safe alternative to methadone in a patient with acquired long QT syndrome, as it did not prolong the QT interval 6.
• A study published in the Journal of Addictive Diseases found that buprenorphine, at commonly used doses, did not prolong the QT interval, whereas high doses of methadone were associated with QT interval prolongation 7.

Comparison with Methadone

• Methadone has been associated with QT interval prolongation and torsades de pointes, particularly at high doses 3, 4, 5, 6, 7.
• Buprenorphine appears to be a safer alternative to methadone in terms of QT interval prolongation, as it does not seem to increase the QT interval at commonly used doses 3, 4, 5, 6, 7.

Clinical Implications

• The findings of these studies suggest that buprenorphine is a safe and effective treatment option for patients with opioid addiction, particularly those who are at risk of QT interval prolongation or torsades de pointes 3, 4, 5, 6, 7.
• Clinicians should consider the potential risks and benefits of buprenorphine and methadone when selecting a treatment option for patients with opioid addiction, and monitor patients closely for signs of QT interval prolongation or other cardiac complications 3, 4, 5, 6, 7.