Loperamide has been available since 1970 and when used within its licensed dose is considered a very safe and effective drug.
Loperamide is licensed within the UK for the symptomatic treatment of acute diarrhoea in adults and children 12 years and over. Loperamide is available in the UK as both Pharmacy and General Sale list products:
- Pharmacy (P) medicine-maximum daily dose 16mg
- General Sale List medicine- maximum daily dose 12mg
Loperamide is a synthetic opioid that is structurally related to pethidine. Loperamide binds to µ receptors in the wall of the GI tract causing reduced peristalsis and increased GI transit time, this allows increased water and electrolyte absorption and leads to an improvement in diarrhoea symptoms.
Loperamide also increases the tone of the anal sphincter reducing faecal incontinence and urgency.
High dose loperamide is sometimes used by specialist centres to control high-volume stoma output for patients with a stoma resulting from an ileostomy, jejunostomy or colostomy (off licence use).
Cardiovascular risks associated with high dose loperamide
There have been reports of cardiac events associated with the use of loperamide. These reports are associated with patients who have used high or very high doses of loperamide either as a drug of abuse or for self-treatment of opioid withdrawal.
The cardiac events reported include
- QT prolongation
- torsade de pointes
- ventricular arrhythmias
- syncope
- cardiac arrest
A European wide review of the reports relating to loperamide has identified 19 cases suggestive of cardiac rhythm disorders linked to loperamide abuse or misuse. In each of the reports loperamide was being used at high doses outside of its licensed indication. In 13 of the 19 reports, QT prolongation or torsade de pointes were recorded with reported doses ranging from 40-80mg up to 800mg daily.
The other 6 reports detail cardiac events including syncope, irregular heartbeat, cardiac arrest, ventricular dysrhythmia and asystole.
Advice for healthcare professionals
A recent Drug Safety Update (September 2017) provided the following advice for healthcare professionals:
- Serious cardiovascular events (such as QT prolongation, torsades de pointes, and cardiac arrest), including fatalities, have been reported in association with large overdoses of loperamide
- Healthcare professionals are reminded that if symptoms of overdose occur, naloxone can be given as an antidote
- Since the duration of action of loperamide (t 1/2 9-14 hours) is longer than that of naloxone (t 1/21-3 hours), repeated treatment with naloxone might be indicated; patients should be monitored closely for at least 48 hours to detect possible CNS depression
- As for all medicines, pharmacists should remind patients not to take more than the recommended dose on the label
- Report all suspected adverse reactions, including those associated with abuse or misuse, to the Yellow Card Scheme yellowcard.mhra.gov.uk/