Does Lomotil (diphenoxylate and atropine) cause side effects?

Lomotil (diphenoxylate and atropine) is a combination of a man-made narcotic and an anticholinergic used to treat acute diarrhea (diarrhea of limited duration). 

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.

Common side effects of Lomotil include

Serious side effects of Lomotil include

Drug interactions of Lomotil include monoamine oxidase inhibitors (MAO's) because the combination can cause severe high blood pressure with the possibility of a cerebrovascular accident (stroke).

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 are the important side effects of Lomotil (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.

Lomotil (diphenoxylate and atropine) side effects list for healthcare professionals

The following serious adverse reactions are described elsewhere in labeling:

At therapeutic doses of Lomotil, the following other adverse reactions have been reported; they are listed in decreasing order of severity, but not of frequency:

The following adverse reactions related to atropine sulfate are listed in decreasing order of severity, but not of frequency:

What drugs interact with Lomotil (diphenoxylate and atropine)?


  • Alcohol may increase the CNS depressant effects of Lomotil and may cause drowsiness. Avoid concomitant use of Lomotil with alcohol.

Other Drugs That Cause CNS Depression

  • The concurrent use of Lomotil with other drugs that cause CNS depression (e.g., barbiturates, benzodiazepines, opioids, buspirone, antihistamines, muscle relaxants), may potentiate the effects of Lomotil.
  • Either Lomotil 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

Does Lomotil (diphenoxylate and atropine) cause addiction or withdrawal symptoms?

Drug Abuse And Dependence

Controlled Substance
  • Lomotil is classified as a Schedule V controlled substance by federal regulation. Diphenoxylate hydrochloride is chemically related to the narcotic analgesic meperidine.
Drug Abuse And Dependence
  • In doses used for the treatment of diarrhea, whether acute or chronic, diphenoxylate has not produced addiction.
  • Diphenoxylate hydrochloride is devoid of morphine-like subjective effects at therapeutic doses.
  • At high doses it exhibits codeine-like subjective effects.
  • The dose which produces antidiarrheal action is widely separated from the dose which causes central nervous system effects.
  • The insolubility of diphenoxylate hydrochloride in commonly available aqueous media precludes intravenous self-administration.
  • A dose of 100 to 300 mg/day, which is equivalent to 40 to 120 tablets, administered to humans for 40 to 70 days, produced opiate withdrawal symptoms.
  • Since addiction to diphenoxylate hydrochloride is possible at high doses, the recommended dosage should not be exceeded.

Treatment & Diagnosis

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Medically Reviewed on 2/1/2021
FDA Prescribing Information

Professional side effects, drug interactions, and addiction sections courtesy of the U.S. Food and Drug Administration.