Diphenoxylate – Probably acts both locally and centrally to reduce intestinal motility.
Atropine – Has anticholinergic activity . However , in this preparation atropine is included in doses below the therapeutic level in an attempt to prevent abuse by deliberate overdosage.

Diarrhea (treatment adjunct) – Diphenoxylate and atropine combination is indicated in adults , as an adjunct to fluid and electrolyte therapy , in the symptomatic treatment of acute and chronic diarrhea . It is not recommended for treatment of diarrhea in children.

a- 1% to 10%: Nervousness ; Restlessness; Dizziness ; Drowsiness ; Headache; Mental Depression ; Paralytic ileus ; Dry mouth ; Toxic megacolon ; Urinary retention and difficult urination ; Blurred vision ; Respiratory depression .
b- < 1%: Abdominal discomfort ; Nausea ; Vomiting ; Pancreatitis ; Stomach cramps ; Tachycardia

Hypersensitivity to diphenoxylate , atropine , or any component of the formulation; Severe liver disease ; Jaundice ; Dehydration ; Narrow – angle glaucoma ; Not for use in children < 2 years of age.

High doses may cause physical and psychological dependence with prolonged use . Use with caution in patients with ulcerative colitis , hepatic dysfunction , alcoholism (active or in remission ) , history of drug abuse or dependence , cardiovascular instability, Down’s syndrome , gallbladder disease or gallstones , GI tract obstruction , hiatal hernia associated with reflux esophagitis, hypertension , hyperthyroidism , hypothyroidism , overflow incontinence , intestinal atony of the elderly or debilitated, myasthenia gravis , prostatic hypertrophy or acute urethral stricture or urinary retention, renal function impairment , and respiratory impairment . Reduction of intestinal motility may be deleterious in diarrhea resulting from shigella , salmonella , toxigenic strains of E. coli , and from pseudomembranous enterocolitis associated with broadspectrum antibiotics . Children may develop signs of atropinism (dryness of skin and mucous membranes , thirst , hyperthermia , tachycardia , urinary retention , flushing) even at the recommended dosages . If there is no response within 48 hours , the drug is unlikely to be effective and should be discontinued. If chronic diarrhea is not improved symptomatically within 10 days at maximum dosage of 20 mg/day , control is unlikely with further use.

Concurrent use of diphenoxylate with other addictive medications , especially CNS depressants with habituating potential , may increase the risk of habituation ; caution is recommended . Concurrent use of alcohol or other CNS depression – producing medications with diphenoxylate may increase the CNS depressant effects of either diphenoxylate or these medications . When tricyclic antidepressants are used concurrently with atropine , their anticholinergic effects may be intensified ; dosage adjustment may be required . Anticholinergics or other medications with anticholinergic action may enhance the effects of atropine during concurrent use. Concurrent use of diphenoxylate with MAO inhibitors , including furazolidone , procarbazine , and selegiline may precipitate hypertensive crisis. Also, MAO inhibitors may block detoxification of atropine, thus potentiating its action . Administration of naltrexone to a patient physically dependent of diphenoxylate will precipitate withdrawal symptoms . Also , naltrexone blocks the antidiarrheal effects of diphenoxylate . Concurrent use of opioid (narcotic) analgesics with diphenoxylate may result in increased risk of severe constipation and additive CNS depressant effects . Diphenoxylate may prolong half – life of drugs metabolized in liver.

Watch for signs of atropinism . Monitor number and consistency of stools.