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# Diphenoxylate and atropine

An opioid antidiarrhoeal related to pethidine, with a little atropine added to discourage misuse. Dangerous in young children.

Updated 2026-11-01

- Class: [Antidiarrhoeals](https://durgical.com/en/pharmacology/classes/antidiarrhoeals/)
- Receptor: μ-opioid receptors of the gut wall
- ATC code: A07DA01

Also called: Co-phenotrope

## Mechanism of action

Diphenoxylate is an opioid related to pethidine (meperidine). It is quickly converted to difenoxin (diphenoxylic acid), which is also active. Acting on the gut wall it increases segmenting contractions and slows propulsion, so contents stay longer in contact with the mucosa. Atropine is present in a subtherapeutic amount so that large doses cause unpleasant anticholinergic effects.

- Diphenoxylate is hydrolysed to active difenoxin
- Acts on gut μ-opioid receptors and smooth muscle
- More segmentation and slower transit reduce stool output
- A small dose of atropine discourages overdose

## Pharmacokinetics

**Metabolism**
Rapid ester hydrolysis to the active metabolite difenoxin (diphenoxylic acid)

**Elimination**
Metabolites in stool and urine

**Half-life**
About 12 to 14 hours for difenoxin

## Indications

- Adjunctive treatment of diarrhoea in patients 13 years and older, together with fluids and electrolytes

## Adverse effects

### Common

- Nausea, vomiting and loss of appetite
- Drowsiness, dizziness and headache
- Restlessness or mood changes
- Dry mouth and skin (atropine)

### Serious (rare, important)

- Respiratory and CNS depression, coma and death in children under 6 years
- Atropine toxicity: fever, fast heart rate, urinary retention, flushing; children with Down syndrome are more sensitive
- Toxic megacolon in acute ulcerative colitis
- Overdose symptoms can be delayed by many hours because gastric emptying slows
- Hepatic coma in advanced liver disease

## Contraindications

- Children under 6 years
- Diarrhoea from C. difficile or invasive or enterotoxin-producing bacteria (toxigenic E. coli, Salmonella, Shigella)
- Obstructive jaundice
- Hypersensitivity to diphenoxylate or atropine

## Key interactions

**MAO inhibitors**
Its pethidine-like structure may, in theory, trigger a hypertensive crisis

**Alcohol, benzodiazepines, barbiturates, other opioids and sedatives**
Added drowsiness and CNS depression

## What is monitored

- Stool frequency, abdominal distension and hydration
- Signs of atropine toxicity (dry skin, flushing, fast pulse, urinary retention)
- Level of consciousness and breathing, especially after overdose
- Liver function in liver disease

## Administration and safety

- Oral only; kept out of reach of children, who are at risk of severe respiratory depression.
- Fluids and electrolytes are corrected first; it is withheld in severe dehydration until they are.
- It is a controlled medicine in some countries because of its opioid content.

## Nursing care

- Ask about bloody stools, fever and recent antibiotics before giving it.
- Assess hydration and electrolytes; replace fluids first.
- Stop and report abdominal distension.
- Teach families to store it locked away from children and to seek help for drowsiness or slow breathing.

## Pregnancy and breastfeeding

Animal studies could not fully assess fetal effects and there are no adequate human studies; it is used in pregnancy only if the benefit justifies the risk.

## Memory aid

Diphenoxylate slows the gut, atropine stops the abuse, but in children under 6 it can stop the breathing.

## Test yourself

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

## Why does this product contain atropine?

A subtherapeutic amount is added so that large doses cause unpleasant anticholinergic effects, discouraging misuse.

## Which age group must not receive it, and why?

Children under 6 years, because of severe respiratory and CNS depression.

## What is the active metabolite of diphenoxylate?

Difenoxin (diphenoxylic acid).

## Which antidepressant class may interact dangerously with diphenoxylate?

MAO inhibitors, with a theoretical risk of hypertensive crisis.

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## Related drugs

- [Loperamide](https://durgical.com/en/pharmacology/loperamide/)

[← 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 - DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d0e2877-7a74-433f-8a31-e3e54aa9dc9f) (DailyMed (U.S. National Library of Medicine), 2026); [Diphenoxylate: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a601045.html) (MedlinePlus (U.S. National Library of Medicine), 2024); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=A07DA) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/diphenoxylate-and-atropine/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/diphenoxylate-and-atropine/