BLACK BOX WARNING
- not recommended in children under 2; can cause respiratory depression, coma, and death
diphenoxylate/atropine
Brand: Lomotil
⚠ BBW ISMP High Alert Beers Criteria
Drug Class: antidiarrheal / opioid agonist
Drug Family: GI agent
Subclass: opioid-based antidiarrheal with anticholinergic
Organ Systems: gastrointestinal
Mechanism of Action
Diphenoxylate activates mu-opioid receptors in the GI myenteric plexus, reducing peristalsis and intestinal secretions to slow transit and allow more water absorption. Atropine is added in subtherapeutic doses to deter abuse; anticholinergic effects further reduce GI motility.
mu-opioid receptors (GI myenteric plexus)muscarinic receptors (atropine component)
Indications
- acute non-specific diarrhea
- chronic diarrhea (adjunct)
Contraindications
- children under 2 years
- infectious diarrhea (invasive bacteria, pseudomembranous colitis)
- obstructive jaundice
- diarrhea associated with organisms that penetrate intestinal mucosa
Adverse Effects
Common
- drowsiness
- dizziness
- constipation
- nausea
- dry mouth (atropine)
Serious
- toxic megacolon (with inflammatory bowel disease)
- respiratory depression (overdose)
- ileus
Pharmacokinetics (ADME)
| Absorption | rapidly absorbed orally; diphenoxylate is converted to active metabolite difenoxin |
| Distribution | crosses BBB (at high doses) |
| Metabolism | hepatic; diphenoxylate converted to difenoxin (active) |
| Excretion | renal and fecal |
| Half-life | 12–14 hours (diphenoxylate/difenoxin) |
| Onset | 45–60 minutes |
| Peak | 2 hours |
| Duration | 3–4 hours |
| Protein Binding | moderate |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| MAOIs | hypertensive crisis risk | major |
| CNS depressants | additive sedation and respiratory depression | major |
| anticholinergics | additive anticholinergic effects from atropine component | moderate |
Nursing Considerations
- Do not use in infectious diarrhea (bacterial invasion or C. difficile) as reducing transit time can worsen infection by delaying clearance of pathogens.
- Schedule II controlled substance due to diphenoxylate; assess abuse potential; dispensed in limited quantities.
- Monitor for toxic megacolon in patients with IBD; discontinue if abdominal distension or decreased bowel sounds develop.
- Warn patients about drowsiness; avoid alcohol and other CNS depressants during use.
Clinical Pearls
- Atropine is added specifically to make the combination aversive at supratherapeutic doses — high diphenoxylate intake causes intolerable anticholinergic effects, discouraging misuse.
- Unlike loperamide, diphenoxylate does cross the BBB, which is why it has Schedule V controlled substance status.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.