Loperamide is an antidiarrhoeal that has been available over the counter for many years. It is a         µ-opioid receptor agonist that inhibits intestinal peristalsis. After oral ingestion it has poor systemic bio-availability and poor blood-brain barrier penetration. Adverse effects are generally mild and short courses do not result in withdrawal symptoms. Due to these factors it was assessed as having low abuse potential.

However, supra-therapeutic doses of loperamide have been reported to overcome these barriers and result in both CNS and respiratory depression. Recent legislative and regulatory changes in the US have limited prescription opioid abuse and opioid-addicted patients are increasingly seeking alternative sources of opioids.

Opioid substitution with loperamide for self-management of opiate withdrawal as well as for euphoria has been reported. Daily doses from 30 to 200 mg or higher have been reported (each tablet contains 2 mg loperamide). Apart from symptoms of opioid toxicity, overdoses of loperamide have been associated with various cardiac dysrhythmias such as ventricular tachycardia and QTc prolongation.

A recent case series in the Annals of Emergency Medicine reported two fatal cases in patients known to be abusing loperamide. Neither autopsy revealed additional findings that may have contributed to death. Although causality could not be proven, the known cardiac toxicity of loperamide and the post-mortem supra-therapeutic levels of loperamide were suggestive (cardiac dysrhythmias do not show up on autopsy).

The authors advise clinicians and pharmacists to be aware of this potential problem of loperamide abuse and resultant possible cardiotoxicity.