Cns Depressants
Severe
Database
Additive CNS/respiratory depression
Avoid combination
Source: Kimi deep-research + Cla
Drug reference
difenoxin
Opioid antidiarrhoeal (active metabolite of diphenoxylate) · Antidiarrheal
START
2 mg PO, then 1 mg after each loose stool
TYPICAL MAX
8 mg/day; stop if no benefit in 48 h
STOP IF
Fever/bloody stool (invasive infection), abdominal distension, or CNS depression
WATCH
Stool pattern, hydration, signs of obstruction; avoid in toxin-mediated colitis
CDSCO approvedATC A07DA04
KDIGO 2024 + manufacturer label
- ONSET
- 1h · absorption
- PEAK
- 2h · Tmax
- t½
- 13h · t½
- DURATION
- 5h · per dose
EXCRETION
Mainly biliary/faecal elimination
route + CYP
INTERACTIONS
2 major
SEVERE in our sources
PREGNANCY
Avoid; limited data.
FDA category + note
Top interactionssee all 4 →
- Cns DepressantsSevereDatabaseKimi deep-research + Cla
- Mao InhibitorsSevereDatabaseKimi deep-research + Cla
Mechanism
Peripheral μ-opioid receptor agonist on intestinal smooth muscle that reduces propulsive motility and increases intestinal water absorption; co-formulated with atropine to deter recreational misuse.
Indications
Acute non-specific diarrhoea (with atropine)
Dosing
- Adult
- Initial 2 mg (2 tablets), then 1 mg (1 tablet) after each loose stool; max 8 mg/day. Discontinue if no improvement in 48 h.
- Pediatric
- Not recommended (<12 y); avoid <2 y.
- Renal adjustment
- No specific adjustment; caution.
- Hepatic adjustment
- Caution in significant hepatic disease.
- Geriatric
- Lower doses; CNS/anticholinergic risk.
- Max dose
- 8 mg/day (4 doses of 2 mg)
Pharmacokinetics
Onset
~1 h
Peak effect
~2 h
Duration
~4–6 h
Half-life
~12–14 h
Bioavailability
~90% (oral)
Protein binding
Moderate
Metabolism
Hepatic
Excretion
Mainly biliary/faecal
Contraindications
- Children <2 years
- Pseudomembranous colitis / antibiotic-associated colitis
- Obstructive jaundice
- Diarrhoea due to invasive pathogens (Salmonella, Shigella, C. difficile)
- Hypersensitivity
Side effects
Common
Dry mouth (atropine)DrowsinessConstipationNauseaDizziness
Serious
- Toxic megacolon (in colitis)
- Respiratory depression (overdose / children)
- CNS depression with alcohol/opioids
- Atropine toxicity (especially children)
Pregnancy & lactation
Pregnancy
Avoid; limited data.
Lactation
Avoid (excreted in milk; neonatal sedation/atropine effects).
Drug interactions
Mao Inhibitors
Severe
Database
Hypertensive crisis (atropine + opioid)
Avoid combination
Source: Kimi deep-research + Cla
Anticholinergics
Moderate
Database
Additive antimuscarinic effects (atropine)
Avoid stacking
Source: Kimi deep-research + Cla
Drugs That Slow Gi Motility
Moderate
Database
Additive ileus/megacolon risk
Avoid in colitis
Source: Kimi deep-research + Cla
8 additional low-confidence interactions hidden — those rows lack a documented mechanism or management plan in our sources.
Related guidelines
Ask House about difenoxin
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Sources: Goodman & Gilman 14e·Verified: 2026-05-20 · House clinical team·Cockpit curated: 2026-05-20