Diphenoxylate HCl – Atropine Sulfate
Action And Clinical Pharmacology: The mode of action of diphenoxylate in the bowel is similar to that of morphine and related drugs. Gastrointestinal propulsion is inhibited through a direct action on the smooth muscle, resulting in a decrease in peristaltic action and a consequent increase in transit time. tag_IndicationsIndications
Indications And Clinical Uses: As an adjunct in the management of diarrhea. Bacterially-induced diarrhea should be treated with appropriate antimicrobial therapy.
Contra-Indications: Known hypersensitivity to diphenoxylate or atropine; patients who are jaundiced; the treatment of diarrhea associated with pseudomembranous enterocolitis; diarrhea caused by enterotoxin producing bacteria.
Manufacturers’ Warnings In Clinical States: This medication should be kept out of the reach of children since accidental overdose may cause severe or even fatal respiratory depression. Lomotil is not recommended for use in children under 2 years of age. Dosage recommendations should be strictly adhered to, especially in children.
Pregnancy and Lactation: The use of Lomotil during pregnancy, lactation or in women of childbearing potential requires that the expected benefits of the drug be weighed against any possible hazard to the mother and child. Effects of diphenoxylate or atropine may be evident in the infants of nursing mothers taking Lomotil (since these compounds are excreted in breast milk).
Precautions: General: Occupational Hazards: Lomotil may produce drowsiness or dizziness. The patient should be cautioned regarding activities that require mental alertness, such as driving or operating dangerous machinery.
Slowing of intestinal motility by an agent such as Lomotil does not preclude the need for appropriate fluid and electrolyte replacement. Dehydration may further influence the variability of response to Lomotil and may predispose to delayed diphenoxylate intoxication. Drug-induced inhibition of peristalsis may result in fluid retention in the colon which may further aggravate dehydration and electrolyte imbalance. If severe dehydration or electrolyte imbalance is present, withhold Lomotil until appropriate corrective therapy has been initiated.
Children: Lomotil should be used with special caution, since signs of atropinism may occur even with recommended doses, particularly in patients with Down’s Syndrome. Lomotil should be used with special caution in young children because of their variable response.
Patients with Special Diseases and Conditions: Lomotil should be used with extreme caution in patients with cirrhosis and other hepatic disease and in all patients with abnormal liver function tests, since hepatic coma may be precipitated.
In some patients with acute ulcerative colitis, agents which inhibit intestinal motility or delay intestinal transit time have been reported to induce toxic megacolon. Consequently, patients with acute ulcerative colitis should be carefully observed and Lomotil therapy should be discontinued promptly if abdominal distension occurs or if other untoward symptoms develop.
Dependence Liability: Addiction to (dependency on) Lomotil is theoretically possible at high dosage. Therefore, the recommended dosage should not be exceeded. Because of the structural and pharmacological similarity of diphenoxylate to meperidine and similar drugs with a definite addiction potential, Lomotil should be administered with considerable caution to patients who are receiving addicting drugs, to individuals known to be addiction-prone, or to those whose histories suggest that they may increase the dosage on their own initiative. Because a subtherapeutic dose of atropine has been added to the diphenoxylate, to discourage deliberate overdosage, there should be strict observance of the contraindications and precautions relative to the use of atropine.
Drug Interactions: Lomotil may potentiate the action of barbiturates, tranquilizers and alcohol. Therefore, the patient should be closely observed when these medications are used concomitantly.
Since the chemical structure of diphenoxylate is similar to that of meperidine, the concurrent use of Lomotil with MAO inhibitors may in theory precipitate a hypertensive crisis.
Adverse Reactions: The most frequently reported adverse effect is nausea. Other symptoms which have been reported at therapeutic doses are: Nervous System: drowsiness, coma, lethargy, sedation/drowsiness, restlessness, dizziness, insomnia, headache, blurring of vision, depression, euphoria, confusion, paresthesia, malaise.
Respiratory: respiratory depression.
Gastrointestinal: vomiting, anorexia, nausea, abdominal bloating, cramps, paralytic ileus, toxic megacolon, pancreatitis.
Allergy: anaphylaxis, pruritus, skin eruption, giant urticaria, angioneurotic edema.
Atropine effects such as dryness of the skin and mucous membranes, hyperthermia, tachycardia, urinary retention and flushing may also occur, especially in children.
Symptoms And Treatment Of Overdose: Symptoms: Initial signs 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. Cardiac arrest has occurred in children. tag_Treatment
Treatment: Treat all possible Lomotil overdoses as serious and maintain medical observation for at least 48 hours.
Gastric lavage, establishment of a patent airway and possibly mechanically assisted respiration are advised. Undertake gastric lavage with due caution in an unconscious patient, preferably following insertion of a cuffed endotracheal tube. If the patient is not comatose, administration of a slurry of activated charcoal may be indicated.
Narcotic antagonists such as naloxone HCl may be used for the treatment of respiratory depression caused by narcotic drugs or pharmacologically-related compounds, such as Lomotil.
Naloxone HCl Dosage in Adults: Naloxone HCl may be administered to adults at a dose of 0.4 mg i.v. Additional doses of 0.4 mg may be given at 2- or 3-minute intervals until adequate improvement in pulmonary ventilation is demonstrated. Subsequent injections of this drug must be governed by the degree of respiratory depression present and should be titrated accordingly. Since the duration of action of naloxone HCl is short in comparison to that of diphenoxylate, improvement of respiration after its administration may be followed by subsequent respiratory depression. It should be noted that although signs of overdosage and respiratory depression may not be evident with Lomotil after ingestion, respiratory depression may occur 12 to 30 hours later. Consequently, continuous observation is necessary until the effect of diphenoxylate on respiration, which may persist for many hours, has passed. The period of observation should extend over at least 48 hours, preferably under continuous hospital care.
Naloxone HCl Dosage in Children: For known or suspected narcotic overdosage, the initial dosage of naloxone HCl in children is 0.005 to 0.01 mg/kg body weight when given i.v., i.m. or s.c. This dose may be repeated as for adults above. If necessary, naloxone HCl can be diluted with sterile water for injection.
Dosage And Administration: Adults: The usual initial dose is 5 mg (2 tablets) 3 or 4 times daily ( 20 mg/24 hours in divided doses is the maximum recommended dosage). An individual maintenance dose can be subsequently determined. Downward adjustment should be made as soon as initial control of symptoms is accomplished. The maintenance dose may be as low as 1/4 of the dose required for initial control.
Children: Not for use in children under 2 years of age (see Warnings and Precautions).
The recommended initial dosage determined by the child’s weight, is 0.3 to 0.4 mg/kg daily in divided doses.
As with adult therapy, adjustment of dosage downward should be made as soon as initial control of symptoms is accomplished.
These pediatric schedules are the best approximation of an average dose recommendation which should be adjusted according to the overall nutritional status and degree of dehydration encountered in the child. The recommended doses must not be exceeded.
Availability And Storage: Each round, white tablet, with “SEARLE” debossed on one side and “61” on the other side, contains: diphenoxylate HCl 2.5 mg and atropine sulfate 0.025 mg. Nonmedicinal ingredients: acacia, cornstarch, magnesium stearate, mineral oil, sorbitol, sucrose and talc. Bottles of 250. Store at temperatures below 30Â°C and protect from light. (Shown in Product Recognition Section)
LOMOTIL® Searle Diphenoxylate HCl – Atropine Sulfate Antidiarrheal