In this episode, I’ll discuss the treatment of loperamide toxicity.

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Loperamide is often referred to as “the poor man’s methadone”. It has been used as both a drug of abuse and as a way of self-treating opioid withdrawal.

The dose used in loperamide abuse far exceeds the labelled 16 mg/day maximum, with some patients taking hundreds of milligrams per day.

The most serious sign of loperamide toxicity is ventricular arrhythmias, including torsades. I’ve taken care of one loperamide toxicity patient who had a QTc that exceeded 700 milliseconds!

This episode will focus on actual and theoretical treatments for cardiac toxicity of loperamide overdose.

Very little data seems to be published on the treatment of loperamide toxicity, so therapies are largely empiric.

As for the treatment of any drug toxicity, I consider 4 possible methods of treatment:

Decontamination

Enhance elimination

Antidote therapy

Supportive care

Decontamination

Loperamide is likely absorbed by activated charcoal. Prescribing information claims that loperamide levels are reduced nine-fold when activated charcoal is given, but I am unable to locate these original articles. In therapeutic doses, loperamide’s peak level is about 5 hours after ingestion. This, coupled with loperamide’s effects on reducing bowel motility suggests considering extending the “window” of when activated charcoal would be appropriate past the typical ~1 hour.

I would consider using activated charcoal if I thought the risk of aspiration was low and the patient had significant toxicity from the loperamide ingestion.

Enhance elimination

There is no data on whether multiple dose activated charcoal (MDAC) would enhance the elimination of loperamide. Guidelines for the use of MDAC recommend using this strategy when there is actual evidence that it might improve outcomes.

There is no data on whether loperamide is removed by dialysis, ion trapping, or other methods to enhance elimination of toxins.

Antidote therapy

It is possible that loperamide’s cardiotoxicity is mediated by sodium channel blockade. If this is the case, giving sodium bicarbonate IV may be effective at temporizing the cardiotoxic effects of loperamide. If sodium bicarbonate is used, be sure to frequently monitor potassium and magnesium levels.

Whether or not IV fat emulsion would work as an antidote for loperamide toxicity is unknown. Loperamide is lipophilic, so in theory fat emulsion should work. The best information I can find is anecdotal reports of success in veterinary medicine. I imagine this would only be something to use in patients if other measures have failed.

Supportive care

Defibrillation, magnesium, amiodarone, lidocaine, and overdrive pacing are all on the menu as possible supportive care treatments for loperamide toxicity. No data exists to recommend any particular supportive treatment over another.

Duration of toxicity

Just one study examines the toxicokinetics of loperamide. In this single case report, the half-life of loperamide initially matched that of therapeutic doses (about 9 hours) but then appeared to be greater than 30 hours. In this patient the cardiac conduction disturbance associated with loperamide took several days to resolve.

Summary

In summary, little can be definitively recommended for the treatment of loperamide toxicity due to a dearth of evidence. Treatment is largely supportive care, and you are likely to set a personal record for the longest QTc interval ever seen!

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