How much does buprenorphine prolong the QTc (QT interval corrected) interval?

Buprenorphine's Effect on QTc Interval

Buprenorphine causes minimal QTc prolongation of approximately 15 milliseconds or less, making it a significantly safer option compared to methadone for patients with cardiac risk factors. 1

Evidence on Buprenorphine and QTc Prolongation

Buprenorphine has been consistently shown to have minimal effects on QTc prolongation across multiple studies:

• The FDA label specifically states that "Thorough QT studies with buprenorphine products have demonstrated QT prolongation ≤ 15 msec" and that this effect does not appear to be mediated by hERG channels 1
• Unlike methadone, buprenorphine is unlikely to be pro-arrhythmic when used alone in patients without risk factors 1
• The European Heart Journal guidelines note that "compared with methadone, buprenorphine causes far less prolongation of the QT interval" 2
• The NCCN guidelines confirm that while FDA guidelines recommend limiting buprenorphine doses to a maximum of 20 mcg/hour due to QTc concerns, it still "may have some advantages over methadone in the context of cancer treatments that prolong QT" 2

Comparative Safety Profile

Multiple comparative studies demonstrate buprenorphine's superior cardiac safety profile:

• A randomized controlled trial found that while 23% of methadone patients and 28% of levomethadyl patients developed QTc prolongation (>470 ms in men or >490 ms in women), none (0%) of the buprenorphine patients did 3
• A prospective study using 24-hour Holter monitoring found that 37% of methadone patients had abnormal QT intervals compared to 0% of buprenorphine patients 4
• A 2013 study found no patients with QTc prolongation (defined as >450 ms) after 1 or 6 months of treatment with either methadone or buprenorphine, though this study used modest methadone doses (<100mg/day) 5

Mechanism of Action

Interestingly, the mechanism by which buprenorphine might cause any QTc prolongation differs from most QT-prolonging drugs:

• Unlike methadone, buprenorphine's QTc effect "cannot be explained by direct hERG channel block" 6
• This non-hERG mechanism may explain why buprenorphine has not been associated with Torsades de Pointes despite causing minimal QTc prolongation 6

Clinical Implications and Risk Factors

When prescribing buprenorphine, consider these risk factors for potential QTc prolongation:

• Hypokalemia
• Bradycardia
• Recent conversion from atrial fibrillation
• Congestive heart failure
• Digitalis therapy
• Baseline QT prolongation
• Subclinical long-QT syndrome
• Severe hypomagnesemia 1

Monitoring Recommendations

For patients with cardiac risk factors:

• Obtain baseline ECG before starting treatment
• Consider ECG monitoring after dose increases
• Discontinue if QTc exceeds 500 ms
• Avoid concomitant use with other QT-prolonging medications when possible 2, 1

Special Populations

• In youth with opioid dependence, a study found no evidence that buprenorphine-naloxone increased QTc to levels that would increase risk for Torsades de Pointes 7
• For pregnant women, ACOG and SMFM note that methadone is known to prolong QTc interval, and caution should be taken if QTc is >450-499 msec, with alternative therapy strongly considered if QTc is ≥500 msec 2

Conclusion

Buprenorphine causes minimal QTc prolongation (≤15 msec) and represents a safer alternative to methadone for patients with cardiac risk factors or those taking other medications that may prolong the QT interval. This makes buprenorphine the preferred option for opioid use disorder treatment in patients with pre-existing cardiac conditions or those at risk for QT prolongation.