Cns Depressants
Severe
Database
Additive CNS / respiratory depression
Avoid combination
Source: Kimi deep-research + Cla
Drug reference
diphenoxylate
Opioid antidiarrhoeal (with atropine; Lomotil) · Antidiarrheal
START
5 mg PO four times daily until controlled, then taper
TYPICAL MAX
20 mg/day; stop if no benefit in 48 h
STOP IF
Fever/bloody stool, abdominal distension, or CNS depression
WATCH
Stool pattern, hydration, signs of obstruction; avoid in toxin-mediated colitis
CDSCO approvedATC A07DA01
KDIGO 2024 + manufacturer label
- ONSET
- 1h · absorption
- PEAK
- 2h · Tmax
- t½
- 12h · metabolite 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
Synthetic opioid agonist (chemically related to meperidine) that activates peripheral μ-opioid receptors in the intestinal myenteric plexus, reducing propulsive motility and increasing water absorption; combined with subtherapeutic atropine to deter recreational abuse.
Indications
Acute non-specific diarrhoea (with atropine)
Dosing
- Adult
- 5 mg PO (2 tablets / 10 mL) 4 times daily until diarrhoea controlled, then titrate down; max 20 mg/day for ≤48 h.
- Pediatric
- 2–12 y: 0.3–0.4 mg/kg/day in 4 divided doses (max 10 mg/day); avoid <2 y.
- Renal adjustment
- No specific adjustment; caution.
- Hepatic adjustment
- Caution in significant hepatic disease.
- Geriatric
- Lower doses; CNS/anticholinergic risk.
- Max dose
- 20 mg/day (4 doses of 5 mg)
Pharmacokinetics
Onset
~45–60 min
Peak effect
~2 h
Duration
~4–6 h
Half-life
Parent ~2.5 h; difenoxin metabolite ~12 h
Bioavailability
Variable
Protein binding
Moderate
Metabolism
Hepatic to active difenoxin (metabolite)
Excretion
Mainly biliary/faecal
Contraindications
- Children <2 years
- Diarrhoea due to pseudomembranous colitis / antibiotic-associated colitis
- Obstructive jaundice
- Diarrhoea due to invasive pathogens (Salmonella, Shigella, C. difficile)
- Hypersensitivity
Side effects
Common
Dry mouth (atropine)DrowsinessConstipationNauseaHeadache
Serious
- Toxic megacolon (in colitis)
- Respiratory depression (overdose / children)
- CNS depression (with alcohol/opioids)
- Atropine toxicity (esp. children)
Pregnancy & lactation
Pregnancy
Avoid; limited data.
Lactation
Avoid (excreted in milk; neonatal sedation/atropine effects).
Drug interactions
Mao Inhibitors
Severe
Database
Hypertensive crisis (opioid + atropine + MAOI)
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 diphenoxylate
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Sources: KD Tripathi 7e, Goodman & Gilman 14e·Verified: 2026-05-20 · House clinical team·Cockpit curated: 2026-05-20