Loperamide

  Issues for Surgery

For acute or chronic diarrhoea, faecal incontinence, or short bowel / intestinal failure / high output stoma (HOS) – loss of symptom control, or risk of increase in stoma output, leading to electrolyte disturbances and dehydration if omitted.

Risk of prolonged ileus if continued following colorectal surgery.

Risk of QT-interval prolongation, particularly at high doses, if continued (see Interaction(s) with Common Anaesthetic Agents and Interaction(s) with other Common Medicines used in the Perioperative Period).

  Advice in the Perioperative period

Elective Surgery
Continue (including combination product) – check electrolytes pre-operatively.

Combination product:

• Imodium Plus^®  (loperamide + simethicone)

Consider an ECG for any patients taking greater than the recommended daily dose of 16mg, particularly those with underlying cardiac disease – see Further Information.

Emergency Surgery
Follow advice as for Elective Surgery.

For patients presenting with acute diarrhoea (Bristol Stool Chart types 5 – 7) that is not clearly attributable to an underlying condition (e.g. inflammatory colitis, overflow) or therapy (e.g. enteral feeding), consider assessing them for Clostridium difficile infection (CDI)¹.

Post-operative Advice
Resume post-operatively, if needed, when next dose due.

Review if patient develops reduced gastrointestinal motility (e.g. ileus) post-operatively.

For patients undergoing Colorectal Surgery with Stoma Formation
If high dose loperamide commenced for management of HOS, follow recommended prescribing advice to reduce the risk of cardiac disorders (see Further Information)

For patients undergoing Stoma Reversal Surgery
If indicated for management of HOS, review the need for loperamide post-operatively.

In the event of an overdose with loperamide, naloxone should be administered as an antidote. The duration of loperamide is longer than that of naloxone (1 – 3 hours), so repeated treatment may be necessary; patients should be monitored closely for at least 48 hours to detect CNS depression².

  Interaction(s) with Common Anaesthetic Agents

QT-Interval Prolongation (see also under Interaction(s) with other Common Medicines used in the Perioperative Period)
Loperamide (mainly in overdose) has an unknown risk of QT-interval prolongation, which might lead to the potentially fatal torsades de pointes arrhythmia. Co-administration with other medicines known to prolong the QT-interval must be based on careful assessment of the potential risks and benefits for each patient^{3, 4}.

Anaesthetic agents that may be used in the perioperative period that are known to, or predicted to, prolong the QT-interval include⁴: -

• desflurane, isoflurane, sevoflurane
• thiopental (theoretical)

Monitor ECG with concurrent use if risk factors for QT-prolongation are also present (increasing age, female sex, cardiac disease, and some metabolic disturbances e.g. hypokalaemia).

  Interaction(s) with other Common Medicines used in the Perioperative Period

Hypokalaemia
Corticosteroids can cause hypokalaemia, increasing the risk of torsades de pointes, which might be additive with the effect of loperamide (mainly in overdose)⁴.

QT-Interval Prolongation (see also under Interaction(s) with other Common Medicines used in the Perioperative Period)
Loperamide (mainly in overdose) has an unknown risk of QT-interval prolongation, which might lead to the potentially fatal torsades de pointes arrhythmia. Co-administration with other medicines known to prolong the QT-interval must be based on careful assessment of the potential risks and benefits for each patient⁴.

Medicines that may be used in the perioperative period that are known to prolong the QT-interval include^{3, 4}: -

• ciprofloxacin*
• clarithromycin*
• domperidone – avoid 
• droperidol*
• erythromycin*
• granisetron – avoid if other risk factors present
• haloperidol*
• ondansetron*
• prochlorperazine*

*Monitor ECG with concurrent use if the risk factors for QT-prolongation are also present (increasing age, female sex, cardiac disease, and some metabolic disturbances e.g. hypokalaemia).

Co-trimoxazole
Use of co-trimoxazole increases the bioavailability of loperamide, apparently by inhibiting its first-pass metabolism⁵. If used concomitantly, monitor for signs of loperamide toxicity, particularly where loperamide is used at high doses.

  Further Information

MHRA/CHM Advice: reports of serious cardiac adverse reactions with high doses of loperamide associated with abuse or misuse (September 2017)²

Serious cardiovascular events (such as QT prolongation, torsades de pointes, and cardiac arrest), including fatalities, have been reported in associated with large overdoses of loperamide.

British Intestinal Failure Alliance (BIFA) Guidance on use of High Dose Loperamide in Patients with Intestinal Failure⁶

A European review of reports worldwide identified 19 cases suggestive of cardiac disorders associated with loperamide abuse and misuse. In all cases, there was evidence of intentional high doses being taken for unapproved indications. From these reports, daily doses in use ranged from 40 – 800mg.

Patients with short bowel / intestinal failure who have high gastrointestinal losses of salt and water may have life threatening metabolic / electrolyte disturbances that result in dehydration with renal failure that can become irreversible. Loperamide reduces intestinal motility and can decrease water and sodium output from an ileostomy by about 20-30%. On the basis that there are no reports of loperamide toxicity in patients with gastrointestinal diseases and as loperamide absorption is likely to be reduced in short bowel patients, BIFA recommend continued use of loperamide therapy (greater than 16mg daily) in these patients.

Recommendations⁶:-

• Perform and ECG in all patients with HOS / fistula before starting high doses loperamide (> 16mg per day) and the QT-interval should be measured and documented. The ECG should be repeated after starting high dose loperamide and then every 3 years if the patient remains on therapy
• If the QT-interval is prolonged cardiac co-morbidities are considered, drugs known to prolong the QT-interval are rationalised and metabolic causes (e.g. hypomagnesaemia) are treated. A cardiologist opinion may be sought
• The total daily dose of loperamide should be less than 80mg
• Loperamide toxicity should be considered in any patient with fainting episodes not accounted for by dehydration or other drugs. It should be considered if there is a QT-interval prolongation on an ECG or a serious ventricular arrythmia including torsades de pointes or cardiac arrest occurs
  
  

  References

1. Department of Health. Updated Guidance on the Diagnosis and Reporting of Clostridium Difficile. Published March 2012. Available at www.gov.uk [Accessed 26^th September 2021]
2. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. https://about.medicinescomplete.com/ [Accessed on 26^th September 2021)
3. Summary of Product Characteristics – Loperamide 2mg Hard Capsules. Tillomed Laboratories Ltd. Accessed via www.medicines.org.uk 26/09/2021 [date of revision of the text 20^th October 2020]
4. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. https://about.medicinescomplete.com/  [Accessed on 26^th September 2021]
5. Loperamide. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. https://about.medicinescomplete.com/  [Accessed 26^th September 2021]
6. Jeremy Nightingale, Uchu Meade and the BIFA Committee. British Intestinal Failure Alliance (BIFA) Position Statement: The use of high dose loperamide in patients with intestinal failure. Date of preparation 23^rd April 2018. Available at www.bapen.org.uk [Accessed 26^th September 2021]