Difenoxin and atropine

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/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.

Nursing Mothers Because of the potential for serious adverse reactions in nursing infants from MOTOFEN ® , a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.