Diphenoxylate/Atropine

Diphenoxylate/Atropine is a prescription medication used to treat diarrhea.

• Diphenoxylate/Atropine is available under the following different brand names: Lomotil.

Adult and pediatric dosage

Tablet

• 2.5mg/0.025mg

Solution

• 2.5mg/0.025mg/5mL

Diarrhea

Adult dosage

• 5 mg diphenoxylate/0.05 mg atropine (2 tablets) orally every 6 hours; not to exceed 20 mg diphenoxylate daily until initial control of diarrhea is achieved (usually 48 hours)
• Maintenance: As low as 25% of the initial daily dosage

Pediatric dosage

• Children younger than 2 years of age: Safety and efficacy not established
• Children 2-13 years of age (liquid formulation only):
  • Initial: 0.3-0.4 mg diphenoxylate/kg/day in 4 divided doses
  • 2 years (11-14 kg): 1.5-3 mL orally every 6 hours
  • 3 years (12-16 kg): 2-3 mL orally every 6 hours
  • 4 years (14-20 kg): 2-4 mL orally every 6 hours
  • 5 years (16-23 kg): 2.5-4.5 mL orally every 6 hours
  • 6-8 years (17-32 kg): 2.5-5 mL orally every 6 hours
  • 9-12 years (23-55 kg): 3.5-5 mL orally every 6 hours
• Children 13 years or older: 5 mg diphenoxylate/0.05 mg atropine orally every 6 hours; not to exceed 20 mg diphenoxylate daily until initial control of diarrhea achieved (usually 48 hours)
• Maintenance: As low as 25% of initial dosage 

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”.

Common side effects of Diphenoxylate/Atropine include:

• drowsiness, 
• dizziness, 
• restlessness, 
• headache, 
• numbness in hands or feet, 
• depression, 
• not feeling well, 
• confusion, 
• feelings of extreme happiness, 
• red or swollen gums, 
• dry mouth, nose, or throat, 
• nausea, 
• vomiting, 
• upset stomach, 
• loss of appetite, 
• skin rash, 
• dry skin, and 
• itching

Serious side effects of Diphenoxylate/Atropine include:

• hives, 
• difficulty breathing, 
• swelling of the face, lips, tongue, or throat, 
• severe constipation, 
• stomach pain, 
• bloating, 
• ongoing or worsening diarrhea, 
• diarrhea that is watery or bloody, 
• severe pain in the upper stomach spreading to the back, 
• fever, 
• flushing (warmth, redness, or tingly feeling), 
• hallucinations, 
• seizure, 
• rapid breathing, 
• weak or shallow breathing, 
• fast heart rate, 
• feeling very thirsty or hot, 
• inability to urinate, 
• heavy sweating, and 
• hot and dry skin

Rare side effects of Diphenoxylate/Atropine include:

• none 

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first

• Diphenoxylate/Atropine has severe interactions with the following drug:
  • alvimopan
• Diphenoxylate/Atropine has serious interactions with at least 26 other drugs.
• Diphenoxylate/Atropine has moderate interactions with at least 246 other drugs.
• Diphenoxylate/Atropine has minor interactions with at least 31 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Contraindications

• Hypersensitivity to diphenoxylate or atropine
• Children aged 6 years or younger owing to risks of respiratory and CNS depression (tablets only)
• Obstructive jaundice
• Diarrhea associated with pseudomembranous enterocolitis or infectious enterotoxin-producing bacteria

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Diphenoxylate/Atropine?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Diphenoxylate/Atropine?”

Cautions

• Cases of severe respiratory depression and coma, leading to permanent brain damage or death reported in children younger than 6 years administered tablets (see Contraindications)
• May cause CNS depression; may impair physical or mental abilities; patients should use caution when performing tasks requiring mental alertness, including operating heavy machinery or driving
• Use should be accompanied by appropriate fluid and electrolyte therapy when indicated; if severe dehydration or electrolyte imbalance is present, the drug should be withheld until appropriate corrective therapy is initiated; drug-induced inhibition of peristalsis may result in fluid retention in the intestine, which may further aggravate dehydration and electrolyte imbalance
• Use with extreme caution in patients with advanced hepatorenal disease and all patients with abnormal liver function; hepatic coma may be precipitated
• Therapy may slow GI motility and may enhance bacterial overgrowth and the release of bacterial endotoxins, which have been reported to result in serious GI complications, including sepsis and prolonged and/or worsening diarrhea
• In patients with acute ulcerative colitis, agents that inhibit intestinal motility or prolong intestinal transit time reported to induce toxic megacolon; patients with acute ulcerative colitis should be carefully observed and therapy discontinued promptly if abdominal distention occurs or if other untoward symptoms develop
• Improvement of symptoms is expected within 48 hours; if no improvement within this time, the drug is unlikely to be effective
• Do not exceed recommended dosage; reduce the initial dosage for maintenance
• Consider the development of adverse reactions associated with the use of atropine; therapy has caused atropine (hyperthermia, tachycardia, urinary retention, flushing, dryness of the skin and mucous membranes) particularly in pediatric patients with Down’s syndrome; therapy is not indicated for use in pediatric patients; monitor patients for signs of atropine
• Diphenoxylate hydrochloride may potentiate the action of other drugs that cause dizziness or drowsiness, including barbiturates, benzodiazepines, and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, and alcohol; the patient should be closely observed when any of these are used concomitantly
• Renal impairment
• Hepatic impairment
• Coadministration with opioids increases the risk of anticholinergic and opioid toxicities; initial presenting symptoms may be delayed by up to 30 hours due to prolonged gastric emptying time induced by diphenoxylate
• Therapy contraindicated in patients with diarrhea associated with organisms that penetrate the GI mucosa; antiperistaltic agents, slow gastrointestinal motility and may enhance bacterial overgrowth and release of bacterial exotoxins; the drug has been reported to result in serious GI complications in patients with infectious diarrhea, including sepsis, prolonged and/or worsened diarrhea; prolonged fever and the delay in resolution of stool pathogens reported in a study of Shigellosis in adults
• Since the chemical structure of diphenoxylate hydrochloride is similar to that of meperidine hydrochloride, concurrent use with monoamine oxidase (MAO) inhibitors may, in theory, precipitate hypertensive crisis

Pregnancy and Lactation

• There are no adequate and well-controlled studies in pregnant women; the drug should be used during pregnancy only if the anticipated benefit justifies the potential risk to the fetus; diphenoxylate hydrochloride was shown to affect fertility in rats when given in doses 50 times human dose; a decrease in maternal weight gain of 30% at 20 mg/kg/day and of 10% at 4 mg/kg/day; at 10 times the human dose (4 mg/kg/day), average litter size was slightly reduced
• Exercise caution when the drug is administered to nursing women, since physicochemical characteristics of major metabolite, diphenoxylate acid, are such that it may be excreted in breast milk and since it is known that atropine is excreted in breast milk.