Diphenoxylate

What is Diphenoxylate?

• Diphenoxylate (Lomotil) is synthetic opioid that primarily affects opiate receptors in the intestine and is used to treat diarrhea.
• It is used as a combination drug with atropine for the treatment of diarrhea.
• Diphenoxylate is an opioid and acts by slowing intestinal contractions; the atropine is present to prevent drug abuse and overdose.

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Diphenoxylate

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What are the uses of this medicine?

• Diphenoxylate (Lomotil) is used adjunctive therapy in the management of diarrhea.
• Diphenoxylate should not be given to children younger than 6 years of age.

How does this medicine work?

• Diphenoxylate (dye” fen ox’ i late) is a synthetic piperidine derivative that acts as a mild opiate receptor agonist (predominant µ type receptors), but is used largely for the treatment of diarrhea rather than pain.
• Diphenoxylate is similar to loperamide and is not structurally related to morphine or codeine, and has minimal euphoric or analgesic effects, largely because it is given in low doses and in fixed combination with atropine.
• Diphenoxylate acts as a potent opiate agonist in the intestine and reduces intestinal motility, causing a slowing of intestinal transport and increased resorption of water and electrolytes, actions that are helpful in treating diarrhea.
• Typically, low doses of atropine are added to diphenoxylate to prevent abuse and excessive intake.
• Through its anticholinergic effects, atropine prevents deliberate over-usage of diphenoxylate by triggering very unpleasant side effects (SEs), such as severe weakness and nausea.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• Known hypersensitivity to diphenoxylate or atropine.
• Obstructive jaundice.
• Diarrhea associated with pseudomembranous enterocolitis or enterotoxin-producing bacteria.
• Pediatric patients less than 6 years of age due to the risks of respiratory and central nervous system (CNS) depression

What drug interactions can this medicine cause?

• Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Be sure to mention any of the following:

• medications containing alcohol (Nyquil, elixirs, others)
• antihistamines
• cyclobenzaprine (Amrix)
• barbiturates such as pentobarbital (Nembutal), phenobarbital, or secobarbital (Seconal)
• benzodiazepines such as alprazolam (Xanax), chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Diastat, Valium), estazolam, flurazepam, lorazepam (Ativan), oxazepam, temazepam (Restoril), and triazolam (Halcion)
• buspirone
• medications for mental illness
• muscle relaxants
• other opioid-containing medications such as meperidine (Demerol)
• sedatives
• sleeping pills
• tranquilizers

Also tell your doctor or pharmacist if you are taking the following medications or have stopped taking them within the past two weeks:

• monoamine oxidase (MAO) inhibitors such as isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar) or tranylcypromine (Parnate).

Is this medicine FDA approved?

• Diphenoxylate in combination with atropine was approved for use in the United States in 1960 and is still widely used to treat acute infectious and nonspecific diarrhea caused by gastroenteritis.

How should this medicine be used?

Recommended dosage: In Adults:

• The recommended initial dosage is two Lomotil tablets four times daily or 10 ml (two regular teaspoonfuls) of Lomotil liquid four times daily (20 mg per day).
• Most patients will require this dosage until initial control has been achieved, after which the dosage may be reduced to meet individual requirements. Control may often be maintained with as little as 5 mg (two tablets or 10 ml of liquid) daily.

In Children:

• The recommended initial total daily dosage of Lomotil liquid for children is 0.3 to 0.4 mg/kg, administered in four divided doses.
• Lomotil is not recommended in children under 6 years of age and should be used with special caution in young children.
• The nutritional status and degree of dehydration must be considered.
• In children under 13 years of age, use Lomotil liquid.
• Do not use Lomotil tablets for this age group.

Administration:

• Diphenoxylate comes as a tablet and solution (liquid) to take by mouth.
• It is usually taken as needed up to 4 times a day.
• The oral solution comes in a container with a special dropper for measuring the dose.
• Ask your pharmacist if you have questions about how to measure a dose.
• Your diarrhea symptoms should improve within 48 hours of treatment with diphenoxylate.
• Your doctor may tell you to decrease your dose as your symptoms improve.
• If your symptoms do not improve or if they get worse within 10 days of treatment, call your doctor and stop taking diphenoxylate.
• Diphenoxylate can be habit-forming. Do not take a larger dose, take it more often, or for a longer period of time than your doctor tells you to.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As tablet and liquid for oral

This medicine is available in fallowing brand namesː

• Colonaid (containing Atropine, Diphenoxylate)
• Di-Atro (containing Atropine, Diphenoxylate)
• Lo-Trol (containing Atropine, Diphenoxylate)
• Logen (containing Atropine, Diphenoxylate)
• Lomanate (containing Atropine, Diphenoxylate)
• Lomotil (containing Atropine, Diphenoxylate)
• Lonox (containing Atropine, Diphenoxylate)
• Low-Quel (containing Atropine, Diphenoxylate)

What side effects can this medication cause?

The most common side effects of this medicine include:

• hyperthermia, tachycardia, urinary retention, flushing, dryness of the skin and mucous membranes.

Additionally, the following side effects have been reported in general use:

• Nervous system: numbness of extremities, euphoria, depression, malaise/lethargy, confusion, sedation/drowsiness, dizziness, restlessness, headache.
• Allergic: anaphylaxis, angioneurotic edema, urticaria, swelling of the gums, pruritus.
• Gastrointestinal system: toxic megacolon, paralytic ileus, pancreatitis, vomiting, nausea, anorexia, abdominal discomfort.

What special precautions should I follow?

• Accidental ingestion of diphenoxylate hydrochloride and atropine sulfate tablets in children, especially in those less than 6 years of age, may result in severe respiratory depression or coma. Instruct patients to take steps to store diphenoxylate hydrochloride and atropine sulfate tablets securely and out of reach of children, and to dispose of unused diphenoxylate hydrochloride and atropine sulfate tablets.
• The use of diphenoxylate hydrochloride and atropine sulfate tablets should be accompanied by appropriate fluid and electrolyte therapy, when indicated. If severe dehydration or electrolyte imbalance is present, diphenoxylate hydrochloride and atropine sulfate tablets should be withheld until appropriate corrective therapy has been initiated.
• Diphenoxylate hydrochloride and atropine sulfate tablets are contraindicated in patients with diarrhea associated with organisms that penetrate the GI mucosa (toxigenic E. coli, Salmonella, Shigella), and pseudomembranous enterocolitis (Clostridium difficile) associated with broad-spectrum antibiotics. Diphenoxylate hydrochloride and atropine sulfate tablets have been reported to result in serious GI complications in patients with infectious diarrhea, including sepsis, prolonged and/or worsened diarrhea.
• In some patients with acute ulcerative colitis, agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Diphenoxylate hydrochloride and atropine sulfate tablets therapy should be discontinued promptly if abdominal distention occurs or if other untoward symptoms develop.
• Since the chemical structure of diphenoxylate hydrochloride is similar to that of meperidine hydrochloride, the concurrent use of diphenoxylate hydrochloride and atropine sulfate tablets with monoamine oxidase (MAO) inhibitors may, in theory, precipitate hypertensive crisis.
• Diphenoxylate hydrochloride and atropine sulfate tablets should be used with extreme caution in patients with advanced hepatorenal disease and in all patients with abnormal liver function since hepatic coma may be precipitated.
• Diphenoxylate has not been linked to serum enzyme elevations during therapy or to clinically apparent liver injury.
• Diphenoxylate hydrochloride may potentiate the action of other drugs that cause dizziness or drowsiness, including barbiturates, benzodiazepines and other sedatives/hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, and alcohol. Therefore, the patient should be closely observed when any of these are used concomitantly.
• Clinical improvement of diarrhea is usually observed within 48 hours. If clinical improvement is not seen within 10 days, discontinue diphenoxylate hydrochloride and atropine sulfate tablets and contact their healthcare provider.
• Alcohol may increase the CNS depressant effects of diphenoxylate hydrochloride and atropine sulfate tablets and may cause drowsiness. Avoid concomitant use of diphenoxylate hydrochloride and atropine sulfate tablets with alcohol.
• Caution should be exercised when diphenoxylate hydrochloride and atropine sulfate tablets are administered to a nursing woman.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• respiratory depression, coma, delirium, lethargy, dryness of the skin and mucous membranes, mydriasis or miosis, flushing, hyperthermia, tachycardia, hypotonia, tachypnea, toxic encephalopathy, seizures and incoherent speech.
• Respiratory depression has been reported up to 30 hours after ingestion.

Management of overdosage:

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• A pure narcotic antagonist (e.g., naloxone) should be used in the treatment of respiratory depression caused by diphenoxylate hydrochloride and atropine sulfate tablets.
• Refer to the prescribing information for naloxone.
• Consider diphenoxylate hydrochloride and atropine sulfate toxicity even in settings of negative toxicology tests.
• Following initial improvement of respiratory function, repeated doses of naloxone hydrochloride may be required to counteract recurrent respiratory depression.

Can this medicine be used in pregnancy?

• There are no adequate and well-controlled studies in pregnant women.
• Diphenoxylate hydrochloride and atropine sulfate tablets should be used during pregnancy only if the anticipated benefit justifies the potential risk to the fetus.

Can this medicine be used in children?

• The safety and effectiveness of diphenoxylate hydrochloride and atropine sulfate tablets have been established in pediatric patients 13 years of age and older as adjunctive therapy in the management of diarrhea.
• The safety and effectiveness of diphenoxylate hydrochloride and atropine sulfate tablets have not been established in pediatric patients less than 13 years of age.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• DIPHENOXYLATE HYDROCHLORIDE
• ATROPINE SULFATE

Inactive ingredients:

• SILICON DIOXIDE
• MICROCRYSTALLINE CELLULOSE
• STARCH, CORN
• STEARIC ACID

Who manufactures and distributes this medicine?

• Mylan Pharmaceuticals Inc.
• Morgantown, WV U.S.A.

What should I know about storage and disposal of this medication?

• Store at 20° to 25°C (68° to 77°F).
• Protect from light.

Full and partial opiod agonists:

• Alfentanil
• Butorphanol
• Codeine
• Diphenoxylate
• Fentanyl
• Heroin
• Hydrocodone
• Hydromorphone
• Levorphanol
• Loperamide
• Meperidine
• Methadone
• Morphine
• Opium
• Oxycodone
• Oxymorphone
• Pentazocine
• Remifentanil
• Sufentanil
• Tramadol

Opiate antagonists:

• Nalmefene
• Naloxegol
• Naloxone
• Naltrexone

• Dailymed label info on Diphenoxylate
• FDA Diphenoxylate

Diphenoxylate Resources
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