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Loperamide (Imodium) and Mitragynine (Kratom) and Risk of Ventricular Arrhythmia

November 7, 2023

Written by Samuel Rouleau

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Loperamide, an over-the-counter antidiarrheal opiate, and mitragynine (kratom) are both associated with ventricular arrhythmia and death.

Cope with diarrhea or risk ventricular arrhythmia with loperamide?
The risk for QTc prolongation and torsades de pointes is well-known with methadone. Recently a WHO database showed that of all adverse events related to loperamide, 6.2% were cardiovascular in nature, with ventricular arrhythmia being the most common, and drug misuse was reported in 82% of these cases. Similarly, mitragynine, an unregulated, herbal opioid used by over 5 million individuals in the U.S., carries risk of inducing ventricular arrhythmia.

Investigators queried drug adverse event reporting databases in the U.S. and Canada (FAERS, CVAR, and CAERS). The primary outcome was ventricular arrhythmia/cardiac arrest, and the secondary outcome was QTc prolongation/torsades de pointes. The drugs studied were: loperamide, diphenoxylate-atropine, and mitragynine. Naltrexone and buprenorphine were used as negative controls, and methadone was used as a positive control. They reported proportionate reporting ratio (PRR) with 95% confidence intervals. PRR compares the ratio of a specific adverse event within a specific drug to the ratio of that same adverse event among all other drugs studied (values above 2.0 were considered a meaningful difference).

After analyzing over 10 million adverse event reports, mitragynine had the highest risk for significant ventricular arrhythmia (PRR 8.9, 95%CI 6.7-11.7), followed by methadone (PRR 6.6, 95%CI 6.2–7.0), and loperamide (PRR 3.2, 95%CI 3.0–3.4). Regarding the secondary outcome of QTc prolongation/torsades, only methadone (PRR 11.9, 95%CI 11.0-12.9) and loperamide (PRR 8.5, 95%CI 7.9-9.1) had associations. Diphenoxylate show no association with either outcome.

How will this change my practice?
I had been aware of the misuse potential of loperamide but had not understood the significant risk for ventricular arrhythmia and QTc prolongation. I will be sure to consider this when prescribing. Also, I was unaware of the extensive use of mitragynine in the U.S., and I will ask about use in the future.

Ventricular Arrhythmias Associated With Over-the-Counter and Recreational Opioids. J Am Coll Cardiol. 2023 Jun 13;81(23):2258-2268. doi: 10.1016/j.jacc.2023.04.009.

What are your thoughts?