diphenoxylate + atropine




Antah Pharma
Full Prescribing Info
Diphenoxylate hydrochloride, atropine sulphate.
Each tablet contains: Diphenoxylate HCl 2.5mg, Atropine Sulphate 0.025mg.
Pharmacology: Diphenoxylate is rapidly and extensively metabolized in man by ester hydrolysis to diphenoxylic acid (difenoxine), which is biologically active and the major metabolite in the blood. After a 5-mg oral dose of carbon- 14 labelled diphenoxylate hydrochloride in ethanolic solution was given to three healthy volunteers, an average of 14% of the drug plus its metabolites was excreted in the urine and 49% in the feces over a four-day period. Urinary excretion of the unmetabolized drug constituted less than 1% of the dose, and diphenoxylic acid plus its glucuronide conjugate constituted about 6% of the dose. In a 16-subject crossover bioavailability study, a linear relationship in the dose range of 2.5 to 10mg was found between the dose of diphenoxylate hydrochloride and the peak plasma concentration, the area under the plasma concentration-time curve, and the amount of diphenoxylic acid excreted in the urine. The average peak plasma concentration of diphenoxylic acid following ingestion of four 2.5mg tablets was 163ng/ml at about 2 hours, and the elimination half-life of diphenoxylic acid was approximately 12 to 14 hours.
Atropine is readily absorbed from the gastro-intestinal tract. It is rapidly cleared from the blood and is distributed throughout the body. It crosses the blood-barrier.
It is incompletely metabolised in the liver and is excreted in the urine as unchanged drug and metabolites. A half-life of about 4 hours has been reported.
In animal, diphenoxylate has a direct effect on circular smooth muscle of the bowel that conceivably results in segmentation and prolongation of gastrointestinal transit time. The clinical antidiarrheal action of diphenoxylate hydrochloride may thus be a consequence of enhanced segmentation that allows increased contact of the intraluminal contents with the intestinal mucosa.
Atropine a naturally occurring alkaloid, is an anticholinergic agent. It acts by competitive inhibition of the actions of acetyl choline on muscarinic receptors. Vagal influences on the gastrointestinal tract are partially inhibited by atropine. Hence, the motor activity in the stomach and small and large intestines is reduced to treat diarrhea.
Sun-Dianox is effective as adjunctive therapy in the management of acute and chronic diarrhea.
Dosage/Direction for Use
Oral administration.
Adults: The recommended initial dosage is 5mg (two tablets) four times daily. 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 5mg (two tablets) daily. Clinical improvement of acute diarrhea is usually observed within 48 hours. If clinical improvement of chronic diarrhea after treatment with a maximum daily dose of 20mg of diphenoxylate hydrochloride is not observed within 10 days, symptoms are unlikely to be controlled by further administration.
Children: Sun-Dianox is not recommended in children under 6 years of age and should be used with special caution in young children (see Precautions).
The recommended initial total daily dosage for children is 0.3 to 0.4mg/kg, administered in four divided doses. The following table provides an approximate initial daily dosage recommendation for children: (See table.)

Click on icon to see table/diagram/image

These pediatric schedules are the best approximation of an average dose recommendation which may be adjusted downward according to the overall nutritional status and degree of dehydration encountered in the sick child. Reduction of dosage may be made as soon as initial control of symptoms has been achieved. Maintenance dosage may be as low as one-fourth of the initial daily dosage. If no response occurs within 48 hours, Sun-Dianox is unlikely to be effective.
Initial signs of overdosage may include dryness of the skin and mucous membranes, mydriasis, restlessness, flushing, hyperthermia, and tachycardia followed by lethargy or coma, hypotonic reflexes, nystagmus, pinpoint pupils, and respiratory depression. Respiratory depression may be evidenced as late as 30 hours after ingestion and may recur despite of an initial response to narcotic antagonist. Treat all possible Sun-Dianox overdosages as serious and maintain medical observation for at least 48 hours, preferably under continuous hospital care.
Treatment: In the event of overdose, induction of vomiting, gastric lavage, establishment of a patent airway, and possibly mechanically assisted respiration are advised. In noncomatose patients, a slurry of 100g of activated charcoal can be administered immediately after the induction of vomiting or gastric lavage. A pure narcotic antagonist (eg. naloxone) should be used in the treatment of respiratory depression caused by Sun-Dianox.
Sun-Dianox is contraindicated in patients with: Known hypersensitivity to diphenoxylate or atropine; Obstructive jaundice; Diarrhea associated with the use of certain antibiotics, pseudomenbranous enterocolitis or enterotoxin-producing bacteria; Intestinal obstruction, acute ulcerative colitis.
Special Precautions
A subtherapeutic dose of atropine has been added to the diphenoxylate hydrochloride. Hence consideration should be given to the precautions relating to the use of atropine. In children, Sun-Dianox should be used with caution since signs of atropinism may occur even with recommended doses, particularly in patients with Down's syndrome. Sun-Dianox may produce drowsiness or dizziness. The patient should be cautioned regarding activities requiring mental alertness, such as driving or operating dangerous machinery. Potentiation of the action of alcohol, barbiturates, and tranquilizers with concomitant use of Sun-Dianox. Diphenoxylate HCl 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.
Appropriate fluid and electrolyte therapy should be given to protect against dehydration in all cases of diarrhoea. Oral rehydration therapy which is the use of appropriate fluids including oral rehydration salts remains the most effective treatment for dehydration due to diarrhoea. The intake of as much of these fluids as possible is therefore imperative. Drug-induced inhibition of peristalsis may result in fluid detention in the intestine, which may aggravate and mask dehydration and depletion of electrolytes, especially in young children. If severe dehydration of electrolyte imbalance is present, diphenoxylate should be withheld until appropriate corrective therapy has been initiated.
Dependence: Short-term administration of diphenoxylate with atropine in the recommended dosage carries a negligible risk of dependence, although prolonged use or use of high doses may produce dependence of the morphine type. Since addiction to diphenoxylate hydrochloride is possible at high doses, the recommended dosage should not be exceeded.
Use in children: The use of diphenoxylate is not recommended for children under 6 years of age. Sun-Dianox should be used with special caution in young children because this age group may be predisposed to delayed diphenoxylate toxicity and because of the greater variability of response in this age group.
Use in elderly: Consideration should be given to the present of other diseases and concomitant drug therapy.
Use In Pregnancy & Lactation
There are no adequate and well-controlled studies in pregnant women. Sun-Dianox should be used during pregnancy only if the anticipated benefit justifies the potential risk to the fetus.
Caution should be exercised when Sun-Dianox is administered to a nursing woman, since the physicochemical characteristics of the major metabolite, diphenoxylic acid, are such that it may be excreted in breast milk and since it is known that atropine is excreted in breast milk.
Adverse Reactions
At therapeutic doses, the following have been reported: 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.
Atropine sulfate effects are hyperthermia, tachycardia, urinary retention, flushing, dryness of the skin and mucous membranes. These effects may occur, especially in children.
Drug Interactions
The concurrent use of diphenoxylate HCl with monoamine oxidase (MAO) inhibitors may, in theory, precipitate hypertensive crisis.
Diphenoxylate hydrochloride may potentiate the action of barbiturates, tranquilizers and alcohol.
Store at or below 30°C. Protect from light.
Shelf-Life: 3 years.
MIMS Class
ATC Classification
A07DA01 - diphenoxylate ; Belongs to the class of antipropulsives. Used in the treatment of diarrhea.
Tab (round, white, deep convex, plain with "S.W." debossed on one side) 10 x 10's, 50 x 10's, 100 x 10's.
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