What is diphenoxylate and atropine, and how does it work (mechanism of action)?

Lomotil is a combination of two drugs, diphenoxylate and atropine. It is used to treat acute diarrhea (diarrhea of limited duration). Diphenoxylate is a man-made narcotic chemically related to meperidine (Demerol). Like other narcotics, diphenoxylate reduces diarrhea by interfering with the propulsion of intestinal contents through the intestines. Although diphenoxylate is chemically related to narcotics, it does not have pain– relieving (analgesic) actions like most other narcotics. In higher doses, however, like other narcotics, diphenoxylate can cause euphoria (elevation of mood) and physical dependence. In order to prevent abuse of diphenoxylate for its mood-elevating effects, atropine is combined with diphenoxylate in small quantities. As a result, if Lomotil is taken in greater than recommended doses unpleasant side effects from too much atropine will occur. Lomotil was approved by the FDA in 1960.

What brand names are available for diphenoxylate and atropine?

Lomotil, Lofene, Lonox

Is diphenoxylate and atropine available as a generic drug?


Do I need a prescription for diphenoxylate and atropine?


What are the side effects of diphenoxylate and atropine?

The most common side effects reported in persons taking diphenoxylate include:

Other important side effects include:

Although the dose of atropine in Lomotil is too low to cause side effects when taken in the recommended doses, side effects of atropine (including dryness of the skin and mucous membranes, increased heart rate, urinary retention, and increased body temperature) have been reported, particularly in children under two years of age and children with Down syndrome. Pancreatitis and toxic megacolon also have been reported.

What is the dosage for diphenoxylate and atropine?

In adults, the usual dose is 5 mg (2 tablets) of diphenoxylate three to four times per day initially. Thereafter, the dose may be decreased to 2.5 mg (1 tablet) two to three times a day. The dose for children (2 to 12 years old) is 0.3 to 0.4 mg/kg/day in four divided doses. If diarrhea is not better within 48 hours, diphenoxylate is not likely to be effective with more prolonged treatment.

Which drugs or supplements interact with diphenoxylate and atropine?

The combination of diphenoxylate and monoamine oxidase inhibitors (MAO’s), for example, isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate), and procarbazine (Matulane) can cause severe high blood pressure with the possibility of a cerebrovascular accident (stroke).

Drugs which increase the propulsion of intestinal contents theoretically can reduce the effectiveness of diphenoxylate. Such drugs include bethanechol (Urecholine), cisapride (Propulsid), metoclopramide (Reglan), and erythromycin.

Drugs which decrease the propulsion of intestinal contents may exaggerate the effects of diphenoxylate and cause constipation. Such drugs include hyoscyamine (Levsin; Cystospaz), antihistamines such as hydroxyzine (Vistaril, Atarax) and diphenhydramine (Benadryl), opiate agonists such as oxycodone (Percocet) and hydrocodone (Vicodin, Norco, etc.), some phenothiazine antipsychotics such as chlorpromazine (Thorazine), thioridazine (Mellaril) and triflupromazine (Stelazine), and some tricyclic antidepressants such as amitriptyline (Elavil, Endep), amoxapine (Asendin), clomipramine (Anafranil), doxepin (Sinequan), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil).

Taking diphenoxylate with alcohol or other chemicals or medications that can depress the central nervous system may cause excessive sedation. Such drugs include barbiturates, benzodiazepines, for example, lorazepam (Ativan), diazepam (Valium), temazepam (Restoril), oxazepam (Serax), or clonazepam (Klonopin), zolpidem (Ambien), narcotics, and tricyclic antidepressants (listed above).

Is diphenoxylate and atropine safe to take if I’m pregnant or breastfeeding?

Adequate studies of diphenoxylate in pregnant women have not been done, so diphenoxylate should be used during pregnancy only when clearly needed.

Diphenoxylic acid, a metabolite of diphenoxylate (that is, diphenoxylate that has been changed chemically by the body) is excreted into breast milk, as is atropine. Although there have not been problems reported in the infants of women who breastfeed, the benefits to the mother should be weighed against the potential risks to the nursing infant.

What else should I know about diphenoxylate and atropine?

What preparations of diphenoxylate and atropine are available?

Tablets (2.5 mg diphenoxylate and 0.025mg atropine); liquid (2.5mg diphenoxylate and 0.025mg atropine per teaspoonsful).

How should I keep diphenoxylate and atropine stored?

Lomotil should be stored at room temperature, 15-30 C (59- 86 F).

Digestive Disorders: Common Misconceptions

Medically Reviewed on 3/1/2019


Medically reviewed by John P. Cunha, DO, FACOEP; Board Certified Emergency Medicine


FDA Prescribing Information