New Study Shows Cardiac Risks With Over-the-Counter Opioids

Volume 28, Issue 2

The opioid epidemic has been raging in this country since the mid-2000s and shows no signs of abating. Starting with prescription drug overdoses in the early 2000s, the opioid crisis entered its third wave in 2013, when synthetic opioids like fentanyl took over as the main culprits for fatal overdoses. 

In light of tightening restrictions on prescription opioids, some patients have turned to over-the-counter (OTC) and natural alternatives. OTC antidiarrheal medications like loperamide have very weak mu receptor properties, so consumption of large quantities of these drugs can produce a mild euphoria. Mitragynine, the herbal ingredient in kratom, also has mild opioid properties. 

Some opioid products like methadone can increase the risk of cardiac arrhythmia. As of now, the proarrhythmic potential of loperamide and mitragynine have not been evaluated. In this week’s issue of Talking Therapeutics, we explore a new study in which researchers looked for associations between OTC opioid products and cardiac arrhythmias.

Point 1: Concerning New Data

In a new paper published in the Journal of the American College of Cardiology this week, investigators mined the US Food and Drug Administration Adverse Event Reporting System, the Center for Food Safety and Applied Nutrition Adverse Event Reporting System, and the Canada Vigilance Adverse Reaction databases for information from 2015 to 2021. Data related to loperamide, mitragynine, and diphenoxylate/atropine were identified. Methadone served as a positive control due to its established arrhythmia risk, while buprenorphine and naltrexone served as negative controls.

Unsurprisingly, the authors found that methadone was significantly associated with ventricular arrhythmia reports (PRR: 6.6; 95% CI: 6.2-7.0; n = 1163; chi-square = 5456), which included 852 (73%) fatalities. Loperamide was also significantly associated with arrhythmia (PRR: 3.2; 95% CI: 3.0-3.4; n = 1008; chi-square = 1537), including 371 (37%) deaths. Surprisingly, mitragynine had the greatest association with arrhythmia reports (PRR: 8.9; 95% CI: 6.7-11.7; n = 46; chi-square = 315), including 42 (91%) deaths. 

No excessive risk of arrythmia was found with buprenorphine, diphenoxylate, and naltrexone. 

Point 2: Public Education Is Key

Considering these data, the US public health system should take action to alert consumers about the risk of fatal arrhythmia with these easily available agents. Pharmacists have a role in this as well, considering that loperamide can be purchased at any pharmacy. Pharmacists should be alert for any patients who are purchasing excessive quantities of loperamide and take action to warn patients about the potentially life-threatening complications.