[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Antidiarrhoeals](https://durgical.com/en/pharmacology/classes/antidiarrhoeals/) › Loperamide

[Pharmacology](https://durgical.com/en/pharmacology/) · [Antidiarrhoeals](https://durgical.com/en/pharmacology/classes/antidiarrhoeals/)

# Loperamide

An opioid that acts on the gut wall and barely reaches the brain. It slows the bowel to control diarrhoea but does not replace fluids.

Updated 2026-11-01

- Class: [Antidiarrhoeals](https://durgical.com/en/pharmacology/classes/antidiarrhoeals/)
- Receptor: μ-opioid receptor of the myenteric plexus
- ATC code: A07DA03
- WHO Model List of Essential Medicines

◎**μ-opioid receptor of the myenteric plexus**Loperamide

ⓘ The figure shows loperamide in the human μ-opioid receptor bound to its Gi protein (cryo-EM); the viewer crops the image to the receptor.

**Target in 3D:** μ-opioid receptor of the myenteric plexus. PDB structure 9PY4 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/9PY4) · Drag to rotate · pinch to zoom

## Mechanism of action

Loperamide binds μ-opioid receptors in the gut wall and reduces the release of acetylcholine and prostaglandins. Propulsive peristalsis slows, contents stay longer in contact with the mucosa, more water and salt are absorbed and stool volume falls. It also raises anal sphincter tone. P-glycoprotein pumps it out of the brain, so at usual doses it has little central effect.

- Binds μ-opioid receptors in the gut wall
- Less acetylcholine and prostaglandin release slows peristalsis
- Longer transit lets more water and salt be absorbed
- P-glycoprotein keeps it out of the brain at usual doses

## Pharmacokinetics

**Absorption**
Very low plasma levels after usual oral doses

**Distribution**
Highly protein bound; a P-glycoprotein substrate, so little enters the brain

**Metabolism**
Liver, mainly by CYP3A4 and CYP2C8 (N-demethylation)

**Elimination**
Mainly in the stool

**Half-life**
About 11 hours

## Indications

- Acute non-specific diarrhoea in patients 2 years and older, together with rehydration [Acute (viral) gastroenteritis →](https://durgical.com/en/conditions/acute-gastroenteritis/)
- Chronic diarrhoea of inflammatory bowel disease in adults
- Diarrhoea in irritable bowel syndrome [Irritable bowel syndrome →](https://durgical.com/en/conditions/irritable-bowel-syndrome/)
- Reducing the output of an ileostomy

## Adverse effects

### Common

- Constipation
- Tiredness
- Dizziness or drowsiness
- Rash or itching

### Serious (rare, important)

- QT prolongation, torsades de pointes, ventricular arrhythmias, syncope and cardiac arrest, mostly above recommended doses or with misuse
- Ileus, megacolon and toxic megacolon
- Respiratory and CNS depression in children under 2 years
- Anaphylaxis (very rare)

## Contraindications

- Children under 2 years
- Abdominal pain without diarrhoea
- Acute dysentery (blood in the stool and high fever)
- Acute ulcerative colitis
- Bacterial enterocolitis from invasive organisms (Salmonella, Shigella, Campylobacter)
- Pseudomembranous colitis (C. difficile) after antibiotics

## Key interactions

**CYP3A4 inhibitors (itraconazole), CYP2C8 inhibitors (gemfibrozil) and P-glycoprotein inhibitors (quinidine, ritonavir)**
Raise loperamide levels: more cardiac and CNS toxicity

**Drugs that prolong the QT interval (class IA and III antiarrhythmics, some antipsychotics, moxifloxacin, methadone)**
Additive risk of torsades de pointes; the combination is avoided

**Saquinavir**
Loperamide lowers saquinavir exposure; antiviral effect is watched

## What is monitored

- Stool frequency and consistency; stop if there is no improvement in acute diarrhoea within 48 hours
- Abdominal distension, constipation or ileus
- Hydration and electrolytes
- ECG and heart rhythm when there are QT risk factors or interacting drugs

## Administration and safety

- Oral only; the recommended maximum per day is never exceeded because of the cardiac risk.
- Fluids and electrolytes remain the base of treatment; loperamide does not replace them.
- Not given to children under 2 years.

## Nursing care

- Ask about blood in the stool, fever and recent antibiotics before giving it; report them because loperamide may be contraindicated.
- Assess hydration (thirst, mucous membranes, urine output) and replace fluids.
- Stop and report if abdominal distension, constipation or ileus appear.
- Teach not to exceed the dose on the label and to seek help for fainting, palpitations or unresponsiveness.
- Review the medication list for QT-prolonging drugs and CYP3A4 or P-glycoprotein inhibitors.

## Pregnancy and breastfeeding

Not usually recommended in pregnancy unless a clinician judges the benefit worth it; small amounts reach breast milk.

## Memory aid

Loperamide «LOPes» the gut, not the brain: μ in the wall, P-glycoprotein at the door, but too much hits the heart (QT).

## Test yourself

Think of the answer, then tap the question to see it.

## Why does loperamide cause few central opioid effects at usual doses?

P-glycoprotein pumps it out of the brain and plasma levels are very low.

## Which cardiac risk is linked to loperamide above recommended doses?

QT prolongation with torsades de pointes, ventricular arrhythmias and cardiac arrest.

## In which situations is loperamide contraindicated?

Children under 2 years, dysentery with blood and fever, invasive bacterial enterocolitis, C. difficile colitis or acute ulcerative colitis.

## Which drug interactions raise loperamide levels?

CYP3A4 inhibitors such as itraconazole, CYP2C8 inhibitors such as gemfibrozil and P-glycoprotein inhibitors such as quinidine or ritonavir.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/loperamide/)

## Related drugs

- [Diphenoxylate and atropine](https://durgical.com/en/pharmacology/diphenoxylate-and-atropine/)
- [Oral rehydration salts](https://durgical.com/en/pharmacology/oral-rehydration-salts/)

## Related conditions

- [Acute (viral) gastroenteritis](https://durgical.com/en/conditions/acute-gastroenteritis/)
- [Irritable bowel syndrome](https://durgical.com/en/conditions/irritable-bowel-syndrome/)

[← Back to the class: Antidiarrhoeals](https://durgical.com/en/pharmacology/classes/antidiarrhoeals/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - LOPERAMIDE HYDROCHLORIDE capsule](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5daab489-eb3f-eca1-e063-6394a90a99d5) (DailyMed (U.S. National Library of Medicine), 2026); [Loperamide: a medicine used to treat diarrhoea - NHS](https://www.nhs.uk/medicines/loperamide/) (NHS (National Health Service, UK), 2024); [Loperamide: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682280.html) (MedlinePlus (U.S. National Library of Medicine), 2018); [RCSB PDB - 9PY4: Primed-state loperamide-mu opioid receptor-Gi GDPbS complex (rebound)](https://www.rcsb.org/structure/9PY4) (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.

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