High-dose loperamide linked to serious cardiac events
A Drug Safety Update from the Medicines and Healthcare products Regulatory Agency (MHRA) has highlighted the risk of cardiac events such as QT prolongation, torsades de pointes and cardiac arrest in patients taking high doses of loperamide as a drug of abuse or for self-treatment of opioid withdrawal.
Loperamide is available for sale in the UK in supermarkets (maximum dosage 12mg daily) and over the counter from pharmacies (maximum dosage 16mg daily) for the symptomatic treatment of acute diarrhea. However, its abuse and misuse among people who are unable to get hold of prescription opioids is a growing problem.
A recent review of worldwide spontaneous reports identified 19 cases of suspected cardiac rhythm disorders associated with loperamide abuse or misuse. In all of these cases, the evidence suggested that high dosages (40–800mg daily) were taken intentionally for unapproved indications. As a result of the review, all manufacturers of loperamide have been asked to update their product information and patient information leaflets to include warnings of the risk of cardiac events associated with high doses.
The MHRA has also reminded healthcare professionals that naloxone can be given as an antidote in the case of loperamide overdose. However, since the duration of action of loperamide is longer than that of naloxone, repeated treatment with naloxone may be needed and patients should be monitored closely for at least 48 hours to detect possible CNS depression.
It is likely that loperamide causes cardiac rhythm disorders at high doses through blockade of potassium channels, leading to QT prolongation and arrhythmias; at extremely high doses, it can also slow cardiac conduction by blocking sodium channels.