Motofen

Clinical summary

Indications and usage 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 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. Warnings and cautions WARNINGS MOTOFEN ® IS NOT AN INNOCUOUS DRUG AND DOSAGE RECOMMENDATIONS SHOULD BE STRICTLY ADHERED TO. MOTOFEN ® IS NOT RECOMMENDED FOR CHILDREN UNDER 2 YEARS OF AGE. OVERDOSAGE MAY RESULT IN SEVERE RESPIRATORY DEPRESSION AND COMA, POSSIBLY LEADING TO PERMANENT BRAIN DAMAGE OR DEATH (SEE OVERDOSAGE ). THEREFORE, KEEP THIS MEDICATION OUT OF THE REACH OF CHILDREN. FLUID AND ELECTROLYTE BALANCE – THE USE OF MOTOFEN® DOES NOT PRECLUDE THE ADMINISTRATION OF APPROPRIATE FLUID AND ELECTROLYTE THERAPY. DEHYDRATION, PARTICULARLY IN CHILDREN, MAY FURTHER INFLUENCE THE VARIABILITY OF RESPONSE TO MOTOFEN ® AND MAY PREDISPOSE TO DELAYED DIFENOXIN INTOXICATION. DRUG-INDUCED INHIBITION OF PERISTALSIS MAY RESULT IN FLUID RETENTION IN THE COLON, AND THIS MAY FURTHER AGGRAVATE DEHYDRATION AND ELECTROLYTE IMBALANCE. IF SEVERE DEHYDRATION OR ELECTROLYTE IMBALANCE IS MANIFESTED, MOTOFEN ® SHOULD BE WITHHELD UNTIL APPROPRIATE CORRECTIVE THERAPY HAS BEEN INITIATED. Ulcerative Colitis – 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 MOTOFEN ® therapy should be discontinued promptly if abdominal distention occurs or if other untoward symptoms develop. Liver and Kidney Disease – MOTOFEN ® should be used with extreme caution in patients with advanced hepatorenal disease and in all patients with abnormal liver function tests since hepatic coma may be precipitated. Atropine – A subtherapeutic dose of atropine has been added to difenoxin hydrochloride to discourage deliberate overdosage. Usage of MOTOFEN ® in recommended doses is not likely to cause prominent anticholinergic side effects, but MOTOFEN ® should be avoided in patients in whom anticholinergic drugs are contraindicated. The warnings and precautions for use of anticholinergic agents should be observed. In children, signs of atropinism may occur even with recommended doses of MOTOFEN ® , particularly in patients with Down’s Syndrome. Drug interactions 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. Pregnancy Pregnancy/Teratogenic Effects Pregnancy Category C. Reproduction studies in rats and rabbits with doses at 31 and 61 times the human therapeutic dose respectively, on a mg/kg basis, demonstrated no evidence of teratogenesis due to MOTOFEN ® . Pregnant rats receiving oral doses of difenoxin hydrochloride/atropine 20 times the maximum human dose had an increase in delivery time as well as a significant increase in the percent of stillbirths. Neonatal survival in rats was also reduced with most deaths occurring within four days of delivery. There are no well controlled studies in pregnant women. MOTOFEN ® should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus.