Symptomatic treatment of mild or uncomplicated travelers’ diarrhea, including that occurring in adult travelers with HIV infection. 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).
Ineffective for prevention of travelers’ diarrhea; may increase incidence of travelers’ diarrhea.
Dosage and Administration
Administration
Oral Administration
In children 2–12 years of age, administer as oral solution using only the calibrated measuring device provided by the manufacturer.
Do not administer in children <2 years of age because of the narrow range between therapeutic and toxic doses in this age group.
Discontinue if symptoms of travelers’ diarrhea persist >48 hours or worsen.
Dosage
Available as diphenoxylate hydrochloride; dosage expressed in terms of the salt. Commercially available only in combination with atropine sulfate (in subtherapeutic quantity to discourage deliberate overdosage).
Pediatric Patients
Diarrhea
Oral
Children 2–12 years of age: Initially, 0.3–0.4 mg/kg daily, given in 4 divided doses.
Approximate Initial Dosage for Children 2–12 Years of Age
Age
Approximate Weight
Dosage in mg (mL of 2.5-mg/5-mL oral solution)
2 years
11–14 kg
0.75–1.5 mg (1.5–3 mL) 4 times daily
3 years
12–16 kg
1–1.5 mg (2–3 mL) 4 times daily
4 years
14–20 kg
1–2 mg (2–4 mL) 4 times daily
5 years
16–23 kg
1.25–2.25 mg (2.5–4.5 mL) 4 times daily
6–8 years
17–32 kg
1.25–2.5 mg (2.5–5 mL) 4 times daily
9–12 years
23–55 kg
1.75–2.5 mg (3.5–5 mL) 4 times daily
Children 13–16 years of age: Initially, 5 mg 3 times daily.
Pediatric dosage schedules are approximations of an average dosage recommendation; adjust dosage downward according to overall nutritional status and degree of dehydration.
Continue dosage at initial levels until symptoms are controlled and then reduce for maintenance as required; not likely to be effective if no response occurs within 48 hours.
Maintenance dosages may be as low as one-fourth the initial daily dosage.
Adults
Diarrhea
Oral
Initially, 5 mg 4 times daily.
Continue dosage at initial level until symptoms are controlled and then reduce for maintenance as required; not likely to be effective for treatment of acute diarrhea if no response occurs within 48 hours.
Maintenance dosage may be as low as one-fourth (e.g., 5 mg daily) the initial daily dosage.
If clinical improvement of chronic diarrhea after treatment with a maximum daily dosage of 20 mg is not observed within 10 days, symptoms are unlikely to be controlled by further administration.
Prescribing Limits
Do not exceed recommended dosage.
Pediatric Patients
Diarrhea
Oral
Children 2–12 years of age: 0.4 mg/kg daily in divided doses.
Overdosage may result in severe respiratory depression and coma, possibly leading to permanent brain damage or death. Adhere strictly to dosage recommendations.
Respiratory depression is possible up to 30 hours after ingestion and may recur despite initial response to an opiate antagonist.
MAO Inhibitors
Because diphenoxylate is structurally similar to meperidine, consider the possibility of hypertensive crisis if diphenoxylate and MAO inhibitors are used concomitantly.
Fluid and Electrolyte Replacement Therapy
Appropriate fluid and electrolyte replacement therapy is recommended, when indicated. If severe dehydration or electrolyte imbalance is present, withhold diphenoxylate until appropriate corrective therapy has been initiated.
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.
Infectious Diarrhea and Pseudomembranous Enterocolitis
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.
Ulcerative Colitis
Toxic megacolon reported with agents that inhibit intestinal motility or prolong intestinal transit time in some patients with acute ulcerative colitis. Carefully observe patients with acute ulcerative colitis; discontinue promptly if abdominal distention occurs or other adverse symptoms develop.
Hepatic Effects
Hepatic coma reported in patients with cirrhosis. Use with extreme caution in patients with cirrhosis, advanced hepatorenal disease, or abnormal liver function tests results. Contraindicated in patients with jaundice.
General Precautions
Prescribing and Dispensing Errors
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.
Fixed Combination
Commercially available only in combination with atropine sulfate. Consider the cautions, precautions, and contraindications associated with atropine.
Abuse Potential
Evidence of physical dependence not reported with recommended dosages. Possibility of dependence when given in high dosage.
Specific Populations
Pregnancy
Category C.
Lactation
Active metabolite (diphenoxylic acid) may be distributed into milk; atropine is distributed into milk. Drug effects may occur in breast-fed infants. Caution advised if used in nursing women.
Pediatric Use
Not recommended for children <2 years of age. Use particular caution in young children due to greater variability of responses to the drug. Consider nutritional status and degree of dehydration. (See Fluid and Electrolyte Replacement Therapy under Cautions.)
Not recommended for treatment of travelers’ diarrhea in infants, children, or adolescents with HIV infection.
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.
Hepatic Impairment
Use with extreme caution in patients with cirrhosis, advanced hepatorenal disease, or abnormal liver function test results, since hepatic coma may be precipitated. Contraindicated in patients with jaundice.
Common Adverse Effects
Nausea, vomiting, abdominal discomfort or distention, sedation, dizziness, pruritus, anorexia, restlessness or insomnia, confusion, headache.
Interactions
Inhibits hepatic microsomal CYP isoenzymes at a dosage of 2 mg/kg daily.
Drugs Metabolized by Hepatic Microsomal Enzymes
Possible pharmacokinetic interaction (increased plasma concentrations of enzyme substrate).
Single doses in the usual therapeutic range produce little or no opiate effect. High doses (40–60 mg) may produce euphoria, suppression of the opiate abstinence syndrome, and physical dependence after chronic administration.
Advice to Patients
Importance of not exceeding recommended dosage.
Consequences of overdosage may include severe respiratory depression and coma that may lead to permanent brain damage or death. Keep out of reach of children and in a child-resistant container.
Risk of drowsiness or dizziness; use caution when driving or operating dangerous machinery.
Importance of avoiding CNS depressants (e.g., alcohol, barbiturates, tranquilizers) during therapy.
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.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
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.
Diphenoxylate Hydrochloride and Atropine Sulfate
Routes
Dosage Forms
Strengths
Brand Names
Manufacturer
Oral
Solution
Diphenoxylate Hydrochloride 2.5 mg/5 mL and Atropine Sulfate 0.025 mg/5 mL
Diphenoxylate Hydrochloride and Atropine Hydrochloride Solution ( C-V)
Roxane
Lomotil® ( C-V; with alcohol 15%)
Pfizer
Tablets
Diphenoxylate Hydrochloride 2.5 mg and Atropine Sulfate 0.025 mg*
Lomotil® ( C-V)
Pfizer
Lonox® ( C-V)
Sandoz
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
