Diphenoxylate and atropine

Drug interactions Alcohol Alcohol may increase the CNS depressant effects of diphenoxylate hydrochloride and atropine sulfate and may cause drowsiness (see WARNINGS ). Avoid concomitant use of diphenoxylate hydrochloride and atropine sulfate with alcohol. Other Drugs that Cause CNS Depression The concurrent use of diphenoxylate hydrochloride and atropine sulfate with other drugs that cause CNS depression (e.g., barbiturates, benzodiazepines, opioids, buspirone, antihistamines, muscle relaxants), may potentiate the effects of diphenoxylate hydrochloride and atropine sulfate (see WARNINGS ).

Either diphenoxylate hydrochloride and atropine sulfate 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 diphenoxylate hydrochloride and atropine sulfate in patients who take MAOIs and monitor for signs and symptoms of hypertensive crisis (headache, hyperthermia, hypertension).

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. Diphenoxylate hydrochloride and atropine sulfate should be used during pregnancy only if the anticipated benefit justifies the potential risk to the fetus.

Nursing mothers Caution should be exercised when diphenoxylate hydrochloride and atropine sulfate is administered to a nursing woman, since the physicochemical characteristics of the major metabolite, diphenoxylic acid, are such that it may be excreted in breast milk and since it is known that atropine is excreted in breast milk.