Class: Antidiarrhea Agents
CAS Number: 3810-80-8
Brands: Lomotil, Lonox
Introduction
Antiperistaltic antidiarrhea agent; synthetic phenylpiperidine-derivative opiate agonist.a b c
Uses for Diphenoxylate Hydrochloride
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
Diphenoxylate Hydrochloride 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.a b c
Do not administer in children <2 years of age because of the narrow range between therapeutic and toxic doses in this age group.a b c
Discontinue if symptoms of travelers’ diarrhea persist >48 hours or worsen.100 102
Dosage
Available as diphenoxylate hydrochloride; dosage expressed in terms of the salt.a b c Commercially available only in combination with atropine sulfate (in subtherapeutic quantity to discourage deliberate overdosage).a b c
Pediatric Patients
Diarrhea
Oral
Children 2–12 years of age: Initially, 0.3–0.4 mg/kg daily, given in 4 divided doses.b c
Approximate Initial Dosage for Children 2–12 Years of Agebc
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.b c
Pediatric dosage schedules are approximations of an average dosage recommendation; adjust dosage downward according to overall nutritional status and degree of dehydration.b c
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.b c
Maintenance dosages may be as low as one-fourth the initial daily dosage.b c
Adults
Diarrhea
Oral
Initially, 5 mg 4 times daily.a b c
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.b c
Maintenance dosage may be as low as one-fourth (e.g., 5 mg daily) the initial daily dosage.a b c
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.b c
Prescribing Limits
Do not exceed recommended dosage.a b c
Pediatric Patients
Diarrhea
Oral
Children 2–12 years of age: 0.4 mg/kg daily in divided doses.b
Children 13–16 years of age: 5 mg 3 times daily.b c
Adults
Diarrhea
Oral
20 mg daily in divided doses.b
Cautions for Diphenoxylate Hydrochloride
Contraindications
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
Acute Toxicity
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
MAO Inhibitors
Because diphenoxylate is structurally similar to meperidine, consider the possibility of hypertensive crisis if diphenoxylate and MAO inhibitors are used concomitantly.a b c
Fluid and Electrolyte Replacement Therapy
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
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.a b c
Ulcerative Colitis
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 Effects
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
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.106 107
Fixed Combination
Commercially available only in combination with atropine sulfate.a b c Consider the cautions, precautions, and contraindications associated with atropine.a b c
Abuse Potential
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
Pregnancy
Category C.a b c
Lactation
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
Pediatric Use
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
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.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
Interactions for Diphenoxylate Hydrochloride
Inhibits hepatic microsomal CYP isoenzymes at a dosage of 2 mg/kg daily.b c
Drugs Metabolized by Hepatic Microsomal Enzymes
Possible pharmacokinetic interaction (increased plasma concentrations of enzyme substrate).b c
Specific Drugs
Drug
|
Interaction
|
Comments
|
|---|
CNS depressants (e.g., alcohol, barbiturates, tranquilizers)
|
Increased CNS depressiona b c
|
Monitor closely if used concomitantlya b c
|
MAO inhibitors
|
Concomitant use theoretically may precipitate hypertensive crisisa b c
|
|
Diphenoxylate Hydrochloride Pharmacokinetics
Absorption
Bioavailability
Peak plasma concentration attained within approximately 2 hours following oral administration.a b c
Bioavailability of Lomotil tablets is approximately 90% that of the oral solution.a b c
Onset
45 minutes to 1 hour.a b c
Duration
3–4 hours.a b c
Distribution
Extent
Active metabolite (diphenoxylic acid) may be distributed into milk.a b c
Elimination
Metabolism
Rapidly and extensively metabolized to diphenoxylic acid (active metabolite); also metabolized to hydroxydiphenoxylic acid.a b c
Elimination Route
Metabolites and their conjugates are excreted slowly, principally in feces via bile; lesser amounts are excreted in urine (<1% as unchanged drug).a b c
Half-life
Diphenoxylate: About 2.5 hours.a b c
Diphenoxylic acid: 3–14 hours.a b c
Stability
Storage
Oral
Tablets
Well-closed, light-resistant containers at 15–30°C.d e
Solution
Tight, light-resistant containers at 15–30°C; avoid freezing.a c
ActionsActions
Acts on smooth muscle of the intestinal tract in a manner similar to that of morphine, inhibiting GI motility and excessive GI propulsion.a
Exhibits little or no analgesic activity.a
Single doses in the usual therapeutic range produce little or no opiate effect.a High doses (40–60 mg) may produce euphoria, suppression of the opiate abstinence syndrome, and physical dependence after chronic administration.a
Advice to Patients
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.)
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.a
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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
|
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Diphenoxylate-Atropine 2.5-0.025MG/5ML Liquid (ROXANE): 60/$20.6 or 180/$56.65
Diphenoxylate-Atropine 2.5-0.025MG Tablets (MYLAN): 30/$15.99 or 90/$45.97
Lomotil 2.5-0.025MG/5ML Liquid (PFIZER U.S.): 60/$35.99 or 180/$89.97
Lomotil 2.5-0.025MG Tablets (PFIZER U.S.): 30/$46.29 or 90/$111.1
Lonox 2.5-0.025MG Tablets (SANDOZ): 60/$27.99 or 120/$52.98
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions April 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
Only references cited for selected revisions after 1984 are available electronically.
100. US Public Health Service (USPHS) and Infectious Diseases Society of America (IDSA) Prevention of Opportunistic Infections Working Group. 2001 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons with human immunodeficiency virus. From HIV/AIDS Treatment Information Services (ATIS) website ()
101. Wolfe MS. Protection of travelers. Clin Infect Dis. 1997;25:177-86.
102. Centers for Disease Control and Prevention. Health information for international travel, 2003–2004. Atlanta, GA: US Department of Health and Human Services; 2003:184-91,226-7,233. Updates available from CDC website ().
103. Anon. Advice for travelers. Med Lett Treat Guid. 2004; 2:33-40.
105. Searle. Lomotil (diphenoxylate hydrochloride with atropine sulfate) liquid and tablets prescribing information (dated Dec 9, 1993). In: Physicians’ desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999:2968-9.
106. Pattishall EN. Dear healthcare provider letter regarding dispensing errors involving Lamictal (lamotrigine). Research Triangle Park, NC: GlaxoSmithKline; undated.
107. Pattishall EN. Dear healthcare provider letter regarding dispensing errors involving Lamictal (lamotrigine). Research Triangle Park, NC: GlaxoSmithKline; 2001 Aug.
a. AHFS drug information 2003. McEvoy GK, ed. Diphenoxylate Hydrochloride. Bethesda, MD: American Society of Health-System Pharmacists; 2003:2738-9.
b. Pharmacia. Lomotil (diphenoxylate hydrochloride with atropine sulfate) liquid and tablets prescribing information. Chicago, IL; 2001 Sep.
c. Roxane Laboratories, Inc. Diphenoxylate hydrochloride and atropine sulfate oral solution prescribing information. Columbus, OH; 2000 Dec.
d. Par Pharmaceutical, Inc. Diphenoxylate hydrochloride and atropine sulfate tablets prescribing information. Spring Valley, NY; 1999 Sep.
e. Geneva Pharmaceuticals. Lonox (diphenoxylate hydrochloride with atropine sulfate) prescribing information. Broomfield, CO; 2001 Nov.
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