Diphenoxylate Hydrochloride

Antiperistaltic antidiarrhea agent; synthetic phenylpiperidine-derivative opiate agonist.a b c

Diarrhea

Adjunctive therapy in the management of diarrhea.b c

Symptomatic treatment of mild or uncomplicated travelers’ diarrhea, including that occurring in adult travelers with HIV infection.100 102 103 Should not be used in travelers with severe diarrhea or with high fever or blood in the stools; these travelers may benefit from short-term treatment with an anti-infective (e.g., a fluoroquinolone).102 103

Ineffective for prevention of travelers’ diarrhea; may increase incidence of travelers’ diarrhea.102

Contraindications

• Known hypersensitivity to diphenoxylate or atropine.b c

• Obstructive jaundice.b c

• Diarrhea associated with pseudomembranous enterocolitis or enterotoxin-producing bacteria.b c

Warnings/Precautions

Warnings

Do not use in patients with diarrhea caused by poisoning until the toxic material is eliminated from the GI tract by gastric lavage or cathartics.a

Do not use in patients with high fever or blood in stools.100 101

Overdosage may result in severe respiratory depression and coma, possibly leading to permanent brain damage or death.b c Adhere strictly to dosage recommendations.a b c

Respiratory depression is possible up to 30 hours after ingestion and may recur despite initial response to an opiate antagonist.a b c

Because diphenoxylate is structurally similar to meperidine, consider the possibility of hypertensive crisis if diphenoxylate and MAO inhibitors are used concomitantly.a b c

Appropriate fluid and electrolyte replacement therapy is recommended, when indicated.a b c If severe dehydration or electrolyte imbalance is present, withhold diphenoxylate until appropriate corrective therapy has been initiated.a b c

Drug-induced inhibition of peristalsis may result in fluid retention in the intestine, which may further aggravate dehydration and electrolyte imbalance; may mask fluid and electrolyte depletion in treatment of acute enteritis, especially in young children.a b c

Antiperistaltic agents may prolong and/or worsen diarrhea resulting from some infections (e.g., those caused by Shigella, Salmonella, toxigenic Escherichia coli) and from pseudomembranous enterocolitis associated with broad spectrum antibiotics; do not use in these conditions.a b c

Toxic megacolon reported with agents that inhibit intestinal motility or prolong intestinal transit time in some patients with acute ulcerative colitis.a b c Carefully observe patients with acute ulcerative colitis; discontinue promptly if abdominal distention occurs or other adverse symptoms develop.a b c

Hepatic coma reported in patients with cirrhosis.a b c Use with extreme caution in patients with cirrhosis, advanced hepatorenal disease, or abnormal liver function tests results.b c Contraindicated in patients with jaundice.a b c

General Precautions

Ensure accuracy of prescription; similarity in spelling of Lomotil (fixed combination of diphenoxylate hydrochloride and atropine sulfate) and Lamictal (lamotrigine, an anticonvulsant agent) may result in errors.106 107

Commercially available only in combination with atropine sulfate.a b c Consider the cautions, precautions, and contraindications associated with atropine.a b c

Evidence of physical dependence not reported with recommended dosages.a b c Possibility of dependence when given in high dosage.a b c

Specific Populations

Category C.a b c

Active metabolite (diphenoxylic acid) may be distributed into milk; atropine is distributed into milk.b c Drug effects may occur in breast-fed infants.b c Caution advised if used in nursing women.a b c

Not recommended for children <2 years of age.a b c Use particular caution in young children due to greater variability of responses to the drug.a b c Consider nutritional status and degree of dehydration.b c (See Fluid and Electrolyte Replacement Therapy under Cautions.)

Not recommended for treatment of travelers’ diarrhea in infants, children, or adolescents with HIV infection.100 102

Consider precautions related to use of atropine in children; use with caution since signs of atropinism may occur even at recommended dosages, particularly in patients with Down’s syndrome.b c

Use with extreme caution in patients with cirrhosis, advanced hepatorenal disease, or abnormal liver function test results, since hepatic coma may be precipitated.a b c Contraindicated in patients with jaundice.a b c

Common Adverse Effects

Nausea, vomiting, abdominal discomfort or distention, sedation, dizziness, pruritus, anorexia, restlessness or insomnia, confusion, headache.a b c

• Importance of not exceeding recommended dosage.a b c

• Consequences of overdosage may include severe respiratory depression and coma that may lead to permanent brain damage or death.a b c Keep out of reach of children and in a child-resistant container.b c

• Risk of drowsiness or dizziness; use caution when driving or operating dangerous machinery.a b c

• Importance of avoiding CNS depressants (e.g., alcohol, barbiturates, tranquilizers) during therapy.a b c

• Importance of seeking medical attention if diarrhea is associated with high fever, chills, or severe cramps, or is persistent or associated with severe fluid loss.101 102 103

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.a b c

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a b c

• Importance of informing patients of other important precautionary information.b c (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Diphenoxylate hydrochloride preparations containing not more than 2.5 mg of the drug combined with not less than 0.025 mg of atropine sulfate are subject to control under the Federal Controlled Substances Act of 1970 as schedule V (C-V) drugs.a

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name