Diphenoxylate

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What it isMu agonist slowing gut transit, combined with subtherapeutic atropine; diarrhea.

Why this oneEffective antidiarrheal where loperamide has failed.

What limits itIt crosses into the CNS at higher doses, so unlike loperamide it can cause euphoria and dependence — the atropine is added to deter that. Avoid in invasive colitis and in young children.

FDA-approved for

diarrhea (~1960)

FDA label

Read the full label on DailyMed ↗

FDA dosing	Population	Start	Target	Max
Adjunctive management of diarrhea	≥13 yr	2 tablets QID	reduce after control; maintenance as low as 2 tablets QD	20 mg/day diphenoxylate (8 tablets/day)

Renal Undefined

Hepatic Undefined

Instructions

Reduce dose to individual requirements after initial control of diarrhea
Discontinue if no improvement of chronic diarrhea within 10 days at maximum dose
Accompany with appropriate fluid and electrolyte therapy

Contraindications

Children <6 years (risk of respiratory and CNS depression)
Diarrhea from pseudomembranous enterocolitis (C. difficile) or enterotoxin-producing bacteria
Obstructive jaundice

Cautions

Respiratory and/or CNS depression, especially in children
Anticholinergic and opioid toxicity, including atropinism
Dehydration and electrolyte imbalance
GI complications in infectious diarrhea
Toxic megacolon in acute ulcerative colitis

Adverse reactions

Numbness of extremities, euphoria, sedation/drowsiness, dizziness, headache
Anticholinergic: dry skin/mucous membranes, tachycardia, urinary retention, flushing, hyperthermia
GI: nausea, vomiting, abdominal discomfort, anorexia
Anaphylaxis, angioedema, urticaria, pruritus

Pregnancy No adequate studies; use only if benefit justifies risk; animal fertility and litter-size effects at high doses.

Lactation Undefined

⚠ BOXED WARNING