TAKE-HOME MESSAGE 
- This large database analysis of American and Canadian patients sought to evaluate the risk of ventricular arrhythmia associated with the use of over-the-counter opioids, specifically loperamide and mitragynine (kratom, an over-the-counter herbal supplement commonly used for opioid withdrawal). The results showed a significant risk of arrhythmia and death associated with loperamide and kratom, with methadone also being evaluated for comparison.
- Loperamide, a commonly used over-the-counter opioid for diarrhea, may be associated with risk of ventricular arrhythmias and death similar to that associated with methadone. Kratom supplements may carry similar risks. Providers should consider these risks in patients with a cardiac history.
Epidemic increases in opioid-related deaths prompted policies limiting prescription opioid access in North America. Consequently, the over-the-counter opioids loperamide (Imodium A-D) and mitragynine (herbal drug, kratom) are increasingly used to avert withdrawal or “get high.” These drugs are not known to be proarrhythmic, yet their widespread use has unmasked malignant arrhythmia hazards in our study. Strong signals for cardiac arrest, ventricular tachycardia, and torsade de pointes were seen in an analysis of more than 10 million pharmacovigilance reports. It remains unclear what proportion of the ventricular arrhythmias associated with these drugs are classified as monomorphic or polymorphic ventricular tachycardia? Loperamide is associated with both QT prolongation and Brugada pattern — via sodium–channel blockade — and kratom has not been adequately studied, suggesting an ongoing need for research.
Editorial Note
Dr. Krantz’s opinions do not reflect the official position of the US FDA.