Motofen

INDICATIONS AND USAGE MOTOFEN ® is indicated as adjunctive therapy in the management of acute nonspecific diarrhea and acute exacerbations of chronic functional diarrhea.

DOSAGE AND ADMINISTRATION The recommended starting dose of MOTOFEN ® tablets in adults is 2 tablets then 1 tablet after each loose stool or 1 tablet every 3 to 4 hours as needed, but the total dosage during any 24-hour treatment period should not exceed 8 tablets. In the treatment of diarrhea, if clinical improvement is not observed in 48 hours, continued administration of this type of medication is not recommended. For acute diarrheas and acute exacerbations of functional diarrhea, treatment beyond 48 hours is usually not necessary. Studies in children below the age of 12 have been inadequate to evaluate the safety and effectiveness of MOTOFEN ® in this age group. MOTOFEN ® is contraindicated in children under 2 years of age.

CONTRAINDICATIONS MOTOFEN ® is contraindicated in patients with diarrhea associated with organisms that penetrate the intestinal mucosa (toxigenic E. coli, Salmonella species, Shigella ) and pseudomembranous colitis associated with broad spectrum antibiotics. Antiperistaltic agents should not be used in the conditions because they may prolong and/or worsen diarrhea. MOTOFEN ® is contraindicated in children under 2 years of age because of the decreased margin of safety of drugs in this class in younger age groups. MOTOFEN ® is contraindicated in patients with a known hypersensitivity to difenoxin, atropine, or any of the inactive ingredients, and in patients who are jaundiced.

ADVERSE REACTIONS In view of the small amount of atropine present (0.025 mg/tablet), such effects such as dryness of the skin and mucous membranes, flushing, hyperthermia, tachycardia and urinary retention are very unlikely to occur, except perhaps in children. Many of the adverse effects reported during clinical investigation of MOTOFEN ® are difficult to distinguish from symptoms associated with the diarrheal syndrome. However, the following events were reported at the stated frequencies: Gastrointestinal: Nausea, 1 in 15 patients; vomiting, 1 in 30 patients; dry mouth, 1 in 30 patients; epigastric distress, 1 in 100 patients; and constipation, 1 in 300 patients. Central Nervous System: Dizziness and light-headedness, 1 in 20 patients; drowsiness, 1 in 25 patients; and headache, 1 in 40 patients; tiredness, nervousness, insomnia and confusion ranged from 1 in 200 to 1 in 600 patients. Other less frequent reactions: Burning eyes and blurred vision occurred in a few cases. The following adverse reactions have been reported in patients receiving chemically-related drugs: numbness of extremities, euphoria, depression, sedation, anaphylaxis, angioneurotic edema, urticaria, swelling of the gums, pruritus, toxic megacolon, paralytic ileus, pancreatitis, and anorexia. THIS MEDICATION SHOULD BE KEPT IN A CHILD-RESISTANT CONTAINER AND OUT OF THE REACH OF CHILDREN SINCE AN OVERDOSAGE MAY RESULT IN SEVERE RESPIRATORY DEPRESSION AND COMA, POSSIBLY LEADING TO PERMANENT BRAIN DAMAGE OR DEATH.

Drug Interactions Since the chemical structure of difenoxin hydrochloride is similar to meperidine hydrochloride, the concurrent use of MOTOFEN ® with monoamine oxidase inhibitors may, in theory, precipitate a hypertensive crisis. MOTOFEN ® may potentiate the action of barbiturates, tranquilizers, narcotics, and alcohol. When these medications are used concomitantly with MOTOFEN ® , the patient should be closely monitored. Diphenoxylate hydrochloride, from which the principal active metabolite difenoxin is derived, was found to inhibit the hepatic microsomal enzyme system at a dose of 2 mg/kg/day in studies conducted with male rats. Therefore, difenoxin has the potential to prolong the biological half-lives of drugs for which the rate of elimination is dependent on the microsomal drug metabolizing enzyme system.

DESCRIPTION Each five-sided dye free MOTOFEN ® tablet contains: 1 mg of difenoxin (equivalent to 1.09 mg of difenoxin hydrochloride) and 0.025 mg of atropine sulfate (equivalent to 0.01 mg of atropine). Difenoxin hydrochloride, 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxylic acid monohydrochloride, is an orally administered antidiarrheal agent which is chemically related to the narcotic meperidine. The structural formula is: Atropine sulfate is present to discourage deliberate overdose. Atropine sulfate, an anticholinergic, is benzeneacetic acid, α-(hydroxymethyl)-, 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester, endo-(±)-, (2:1) (salt), monohydrate and has the following structural formula: Inactive Ingredients: calcium stearate, cellulose, lactose, corn starch. Difenoxin Hydrochloride Atropine Sulfate

OVERDOSAGE Diagnosis and Treatment In the event of overdosage (initial signs may include dryness of the skin and mucous membranes, flushing, hyperthermia and tachycardia followed by lethargy or coma, hypotonic reflexes, nystagmus, pinpoint pupils and respiratory depression) gastric lavage, establishment of a patent airway and possibly mechanically assisted respiration are advised. The narcotic antagonist naloxone may be used in the treatment of respiratory depression caused by narcotic analgesics of pharmacologically related compounds such as MOTOFEN ® tablets. When naloxone is administered intravenously, the onset of action is generally apparent within two minutes. Naloxone may be administered subcutaneously or intramuscularly providing a slightly less rapid onset of action but a more prolonged effect. To counteract respiratory depression caused by MOTOFEN ® overdosage, the following dosage schedule for naloxone should be followed: Adult Dosage: The usual initial adult dose of naloxone is 0.4 mg (one mL) administered intravenously. If respiratory function does not adequately improve after the initial dose, the same IV dose may be repeated at two-to-three minute intervals. Children: The usual adult dose of naloxone for children is 0.01 mg/kg of body weight administered intravenously and repeated at two-to-three minute intervals if necessary. Since the duration of action of difenoxin hydrochloride is longer than that of naloxone, improvement of respiration following administration may be followed by recurrent respiratory depression. Consequently, continuous observation is necessary until the effect of difenoxin hydrochloride on respiration (which effect may persist for many hours) has passed. Supplemental intramuscular doses of naloxone may be utilized to produce a longer lasting effect. TREAT ALL POSSIBLE MOTOFEN ® OVERDOSAGES AS SERIOUS AND MAINTAIN MEDICAL OBSERVATION FOR AT LEAST 48 HOURS, PREFERABLY UNDER CONTINUOUS HOSPITAL CARE. Although signs of overdosage and respiratory depression may not be evident soon after ingestion of difenoxin hydrochloride, respiratory depression may occur from 12 to 30 hours later.

HOW SUPPLIED MOTOFEN ® is available as a white, dye-free, five-sided, scored tablet with “0200” on the scored side and "M" on the other side. Each tablet contains 1 mg difenoxin and 0.025 mg atropine sulfate. Supplied in bottles of 100 tablets (NDC 83107-011-10). Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].