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Pronunciation
(dye fen OKS i late & A troe peen)
Generic Available (U.S.)
Yes
Index Terms
Controlled Substance
C-V
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Treatment of diarrhea
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects were not noted in animal studies; decreased maternal weight, fertility and litter sizes were observed. There are no adequate and well-controlled studies in pregnant women.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Atropine is excreted in breast milk (refer to Atropine monograph); the manufacturer states that diphenoxylic acid may be excreted in breast milk.
Contraindications
Hypersensitivity to diphenoxylate, atropine, or any component of the formulation; obstructive jaundice; diarrhea associated with pseudomembranous enterocolitis or enterotoxin-producing bacteria; not for use in children <2 years of age
Warnings/Precautions
Concerns related to adverse effects:
• Dehydration/electrolyte imbalance: In case of severe dehydration or electrolyte imbalance, withhold diphenoxylate/atropine treatment until corrective therapy has been initiated. Use in conjunction with fluid and electrolyte therapy when appropriate. Inhibiting peristalsis may lead to fluid retention in the intestine aggravating dehydration and electrolyte imbalance.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
• Ulcerative colitis: Use with caution in patients with acute ulcerative colitis.
Special populations:
• Pediatrics: Use with caution in children. Younger children may be predisposed to toxicity; signs of atropinism may occur even at recommended doses, especially in patients with Down syndrome. Overdose in children may result in severe respiratory depression, coma, and possibly permanent brain damage.
Other warnings/precautions:
• Appropriate use: If there is no response within 48 hours, this medication is unlikely to be effective and should be discontinued; if chronic diarrhea is not improved symptomatically within 10 days at maximum dosage, control is unlikely with further use. Reduction of intestinal motility may be deleterious in diarrhea resulting from Shigella, Salmonella, toxigenic strains of E. coli, and pseudomembranous enterocolitis associated with broad-spectrum antibiotics; use is not recommended.
• Dependence: Physical and psychological dependence have been reported with higher than recommended dosing.
Adverse Reactions
Frequency not defined.
Cardiovascular: Tachycardia
Central nervous system: Confusion, depression, dizziness, drowsiness, euphoria, flushing, headache, hyperthermia, lethargy, malaise, restlessness, sedation
Dermatologic: Angioneurotic edema, dry skin, pruritus, urticaria
Gastrointestinal: Abdominal discomfort, anorexia, gum swelling, nausea, pancreatitis, paralytic ileus, toxic megacolon, vomiting, xerostomia
Genitourinary: Urinary retention
Neuromuscular & skeletal: Numbness
Miscellaneous: Anaphylaxis
Metabolism/Transport Effects
None known.
Drug Interactions
AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Risk C: Monitor therapy
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Levocabastine (Nasal); Paliperidone. Risk C: Monitor therapy
Cannabinoids: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoids. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Risk C: Monitor therapy
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Risk D: Consider therapy modification
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Risk C: Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Mechanism of Action
Diphenoxylate inhibits excessive GI motility and GI propulsion; commercial preparations contain a subtherapeutic amount of atropine to discourage abuse
Pharmacodynamics/Kinetics
Atropine: See Atropine monograph.
Diphenoxylate:
Onset of action: Antidiarrheal: 45-60 minutes
Duration: Antidiarrheal: 3-4 hours
Absorption: Well absorbed
Metabolism: Extensively hepatic via ester hydrolysis to diphenoxylic acid (active)
Half-life elimination: Diphenoxylate: 2.5 hours; Diphenoxylic acid: 12-14 hours
Time to peak, serum: 2 hours
Excretion: Primarily feces (49% as unchanged drug and metabolites); urine (~14%, <1% as unchanged drug)
Dosage
Oral:
Children 2-12 years (use with caution in young children due to variable responses): Liquid: Diphenoxylate 0.3-0.4 mg/kg/day in 4 divided doses until control achieved (maximum: 10 mg/day), then reduce dose as needed; some patients may be controlled on doses as low as 25% of the initial daily dose
Adults: Diphenoxylate 5 mg 4 times/day until control achieved (maximum: 20 mg/day), then reduce dose as needed; some patients may be controlled on doses of 5 mg/day
Administration: Oral
If there is no response within 48 hours of continuous therapy, this medication is unlikely to be effective and should be discontinued; if chronic diarrhea is not improved symptomatically within 10 days at maximum dosage, control is unlikely with further use. Use of the liquid preparation is recommended in children <13 years of age; use plastic dropper provided when measuring liquid.
Monitoring Parameters
Watch for signs of atropinism (dryness of skin and mucous membranes, tachycardia, thirst, flushing); monitor number and consistency of stools; observe for signs of toxicity, fluid and electrolyte loss, hypotension, and respiratory depression
Patient Education
See individual agents.
Geriatric Considerations
Elderly are particularly sensitive to fluid and electrolyte loss. This generally results in lethargy, weakness, and confusion. Repletion and maintenance of electrolytes and water are essential in the treatment of diarrhea. Drug therapy must be limited in order to avoid toxicity with this agent.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Significant xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause nervousness, restlessness, drowsiness, or insomnia; rarely may produce euphoria
Mental Health: Effects on Psychiatric Treatment
Concurrent use with MAO inhibitors may result in hypertensive crisis; additive sedation and dry mouth with psychotropics; use with benztropine or other anticholinergic agents may result in ileus
Nursing: Physical Assessment/Monitoring
See individual agents.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, oral: Diphenoxylate hydrochloride 2.5 mg and atropine sulfate 0.025 mg per 5 mL (5 mL, 10 mL, 60 mL)
Lomotil®: Diphenoxylate hydrochloride 2.5 mg and atropine sulfate 0.025 mg per 5 mL (60 mL) [contains alcohol 15%; cherry flavor] [DSC]
Tablet, oral: Diphenoxylate hydrochloride 2.5 mg and atropine sulfate 0.025 mg
Lomotil®: Diphenoxylate hydrochloride 2.5 mg and atropine sulfate 0.025 mg
Pricing: U.S. (www.drugstore.com)
Liquid (Diphenoxylate-Atropine)
2.5-0.025 mg/5 mL (60): $20.60
Liquid (Lomotil)
2.5-0.025 mg/5 mL (60): $30.87
Tablets (Diphenoxylate-Atropine)
2.5-0.025 mg (30): $14.99
Tablets (Lomotil)
2.5-0.025 mg (30): $44.09
References
Cutler EA, Barrett GA, Craven PW, et al, “Delayed Cardiopulmonary Arrest After Lomotil® Ingestion,” Pediatrics, 1980, 65(1):157-8.
Ginsburg GM, “Lomotil® (Diphenoxylate and Atropine) Intoxication,” Am J Dis Child, 1973, 125(2):241-2.
Karim A, Ranney RE, Evernsen KL, et al, “Pharmacokinetics and Metabolism of Diphenoxylate in Man,” Clin Pharmacol Ther, 1972, 13(3):407-19.
McCarron MM, Challoner KR, and Thompson GA, “Diphenoxylate-Atropine (Lomotil®) Overdose in Children: An Update (Report of Eight Cases and Review of the Literature),” Pediatrics, 1991, 87(5):694-700.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
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