A European review of worldwide spontaneous reports identified 19 cases suggestive of cardiac rhythm disorders associated with loperamide abuse and misuse. In all cases, there was evidence of intentional high doses being taken for unapproved indications.
The MHRA has reminded healthcare professionals that the opioid antagonist naloxone can be given as an antidote in the event of loperamide overdose.
Since the duration of action of loperamide is longer than that of naloxone (1–3 hours), repeated treatment with naloxone might be indicated. Patients should be monitored closely for at least 48 hours to detect possible CNS depression.
When taken in high doses loperamide may block potassium channels, leading to QT prolongation and arrhythmias. At extremely high concentrations, loperamide also has the potential to slow cardiac conduction via inhibition of sodium channels, and produce conduction arrhythmias.