Lomotil

INDICATIONS AND USAGE Lomotil is indicated as adjunctive therapy in the management of diarrhea in patients 13 years of age and older.

DOSAGE AND ADMINISTRATION Management of Diarrhea in Patients 13 Years of Age and Older Lomotil is recommended as adjunctive therapy for the management of diarrhea in patients 13 years of age and older. Consider the nutritional status and degree of dehydration in patients prior to initiating therapy with Lomotil. The use of Lomotil should be accompanied by appropriate fluid and electrolyte therapy, when indicated. If severe dehydration or electrolyte imbalance is present, do not administer Lomotil until appropriate corrective therapy has been indicated (see WARNINGS ). Initial and Maximum Recommended Dosage in Patients 13 Years of Age and Older The initial adult dosage is 2 Lomotil tablets four times daily (maximum total daily dose of 20 mg per day of diphenoxylate hydrochloride). Most patients will require this dosage until initial control of diarrhea has been achieved. Clinical improvement of acute diarrhea is usually observed within 48 hours. Dosage after Initial Control of Diarrhea After initial control has been achieved, the Lomotil dosage may be reduced to meet individual requirements. Control may often be maintained with as little as two Lomotil tablets daily. Duration of Treatment If clinical improvement of chronic diarrhea after treatment with the maximum recommended daily dosage is not observed within 10 days, discontinue Lomotil as symptoms are unlikely to be controlled by further administration.

CONTRAINDICATIONS Lomotil is contraindicated in: • Pediatric patients less than 6 years of age due to the risks of respiratory and central nervous system (CNS) depression (see WARNINGS ). • Patients with diarrhea associated with pseudomembranous enterocolitis ( Clostridium difficile ) or other enterotoxin-producing bacteria due to the risk of gastrointestinal (GI) complications, including sepsis (see WARNINGS ). • Patients with known hypersensitivity to diphenoxylate or atropine. • Patients with obstructive jaundice.

WARNINGS Respiratory and/or CNS Depression in Pediatric Patients Less Than 6 Years of Age Cases of severe respiratory depression and coma, leading to permanent brain damage or death have been reported in patients less than 6 years of age who received Lomotil. Lomotil is contraindicated in patients less than 6 years of age due to these risks (see CONTRAINDICATIONS ). Anticholinergic and Opioid-Toxicities Toxicities associated with the atropine and diphenoxylate components of Lomotil have been reported. The initial presenting symptoms may be delayed by up to 30 hours due to prolonged gastric emptying time induced by diphenoxylate hydrochloride. Clinical presentations vary in terms of which toxicity (anticholinergic vs. opioid) will present first or predominate; non-specific findings have been reported and include symptoms such as drowsiness (see OVERDOSAGE ). Dehydration and Electrolyte Imbalance The use of Lomotil should be accompanied by appropriate fluid and electrolyte therapy, when indicated. If severe dehydration or electrolyte imbalance is present, Lomotil should be withheld until appropriate corrective therapy has been initiated. Drug-induced inhibition of peristalsis may result in fluid retention in the intestine, which may further aggravate dehydration and electrolyte imbalance. Gastrointestinal Complications in Patients with Infectious Diarrhea Lomotil is 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 (see CONTRAINDICATIONS ). Antiperistaltic agents, including Lomotil, slow gastrointestinal motility and may enhance bacterial overgrowth and the release of bacterial exotoxins. Lomotil 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 the resolution of stool pathogens were reported in study of Shigellosis in adults who used Lomotil vs. placebo. Toxic Megacolon in Patients with Acute Ulcerative Colitis In some patients with acute ulcerative colitis, agents that inhibit intestinal motility or prolong 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 distention occurs or if other untoward symptoms develop. Interaction with Meperidine Hydrocholoride Since the chemical structure of diphenoxylate hydrochloride is similar to that of meperidine hydrochloride, the concurrent use of Lomotil with monoamine oxidase (MAO) inhibitors may, in theory, precipitate hypertensive crisis. Hepatorenal Disease Lomotil 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. Interaction with CNS Depressants 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.

Drug interactions: Alcohol Alcohol may increase the CNS depressant effects of Lomotil and may cause drowsiness (see WARNINGS ). Avoid concomitant use of Lomotil with alcohol. Other Drugs that Cause CNS Depression The concurrent use of Lomotil with other drugs that cause CNS depression (e.g., barbiturates, benzodiazepines, opioids, buspirone, antihistamines, muscle relaxants), may potentiate the effects of Lomotil (see WARNINGS ). Either Lomotil or the other interacting drug should be chosen, depending on the importance of the drug to the patient. If CNS-acting drugs cannot be avoided, monitor patients for CNS adverse reactions. MAO Inhibitors Diphenoxylate may interact with monoamine oxidase inhibitors (MAOIs) and precipitate a hypertensive crisis. Avoid use of Lomotil in patients who take MAOIs and monitor for signs and symptoms of hypertensive crisis (headache, hyperthermia, hypertension).

ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in labeling: • Respiratory and/or CNS depression (see WARNINGS ) • Anticholinergic and opioid-toxicities, including atroponism (see WARNINGS and PRECAUTIONS ) • Dehydration and electrolyte imbalance (see WARNINGS ) • GI Complications in patients with infectious diarrhea (see WARNINGS ) • Toxic megacolon in patients with acute ulcerative colitis (see WARNINGS ) At therapeutic doses of Lomotil, the following other adverse reactions have been reported; they are listed in decreasing order of severity, but not of frequency: Nervous system: numbness of extremities, euphoria, depression, malaise/lethargy, confusion, sedation/drowsiness, dizziness, restlessness, headache, hallucination Allergic: anaphylaxis, angioneurotic edema, urticaria, swelling of the gums, pruritus Gastrointestinal system: megacolon, paralytic ileus, pancreatitis, vomiting, nausea, anorexia, abdominal discomfort The following adverse reactions related to atropine sulfate are listed in decreasing order of severity, but not of frequency: hyperthermia, tachycardia, urinary retention, flushing, dryness of the skin and mucous membranes.

Pregnancy Diphenoxylate hydrochloride has been shown to have an effect on fertility in rats when given in doses 50 times the human dose (see above discussion). Other findings in this study include 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. Teratology studies were conducted in rats, rabbits, and mice with diphenoxylate hydrochloride at oral doses of 0.4 to 20 mg/kg/day. Due to experimental design and small numbers of litters, embryotoxic, fetotoxic, or teratogenic effects cannot be adequately assessed. However, examination of the available fetuses did not reveal any indication of teratogenicity. There are no adequate and well-controlled studies in pregnant women. Lomotil should be used during pregnancy only if the anticipated benefit justifies the potential risk to the fetus.