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
Receptor: μ-opioid receptor of the myenteric plexus
ATC code: A07DA03
WHO Model List of Essential Medicines

μ-opioid receptor of the myenteric plexusLoperamide

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

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 →
Chronic diarrhoea of inflammatory bowel disease in adults
Diarrhoea in irritable bowel syndrome Irritable bowel syndrome →
Reducing the output of an ileostomy

Adverse effects

Common

Constipation
Tiredness
Dizziness or drowsiness
Rash or itching

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.

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.

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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 (DailyMed (U.S. National Library of Medicine), 2026); Loperamide: a medicine used to treat diarrhoea - NHS (NHS (National Health Service, UK), 2024); Loperamide: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2018); RCSB PDB - 9PY4: Primed-state loperamide-mu opioid receptor-Gi GDPbS complex (rebound) (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.