|Diphenoxylate||Mu opiate receptor agonist|
|Atropine||Muscarinic acetylcholine receptors antagonist|
|AHFS/Drugs.com||Professional Drug Facts|
Diphenoxylate/atropine, also known as co-phenotrope, is a combination of the medications diphenoxylate and atropine, used to treat diarrhea. It should not be used in those in whom Clostridioides difficile infection is a concern. It is taken by mouth. Onset is typically within an hour.
Side effects may include abdominal pain, angioedema, glaucoma, heart problems, feeling tired, dry mouth, and trouble seeing. It is unclear if use in pregnancy is safe and use when breastfeeding may result in side effects in the baby. It works by decreasing contractions of the bowel.
The combination was approved for medical use in the United States in 1960. It is available as a generic medication.  In 2019, it was the 339th most commonly prescribed medication in the United States, with more than 900 thousand prescriptions. It is sold under the brand name Lomotil among others. The medication is in Schedule V in the United States.
- Patients under 6 years of age
- Allergy to diphenoxylate or atropine
- Diarrhea associated with pseudomembranous enterocolitis, diarrhea caused by antibiotic treatment, or diarrhea caused by enterotoxin-producing bacteria, such as Clostridium difficile
- Obstructive jaundice
The drug combination is generally safe in short-term use and with recommended dosage. In doses used for the treatment of diarrhea, whether acute or chronic, diphenoxylate has not produced addiction.
It may cause several side-effects, such as dry mouth, headache, constipation and blurred vision. Since it may also cause drowsiness or dizziness, it should not be used by motorists, operators of hazardous machinery, etc. It is not recommended for children under two years of age.
Interactions with other drugs:
- Antidepressants (e.g. Elavil, Prozac)
- Monoamine oxidase inhibitors (e.g. Nardil, Parnate)
- Opioid analgesics
- Sedatives (e.g. Ambien, Sonata)
It may cause serious health problems when overdosed. Signs and symptoms of adverse effects may include any or several of the following: convulsions, respiratory depression (slow or stopped breathing), dilated eye pupils, nystagmus (rapid side-to-side eye movements), erythema (flushed skin), gastrointestinal constipation, nausea, vomiting, paralytic ileus, tachycardia (rapid pulse), drowsiness and hallucinations. Symptoms of toxicity may take up to 12 hours to appear.
Mechanism of action
Diphenoxylate is anti-diarrheal and atropine is anticholinergic. A subtherapeutic amount of atropine sulfate is present to discourage deliberate overdosage. Atropine has no anti-diarrheal properties, but will cause tachycardia when overused. The medication diphenoxylate works by slowing down the movement of the intestines. In some cases it has been shown to ease symptoms of opiate withdrawal.
Society and culture
As of 2018, the combination drug is marketed in the US and some other countries under the following brands: Atridol, Atrolate, Atrotil, Co-Phenotrope, Dhamotil, Dimotil, Intard, Logen, Lomanate, Lomotil, Lonox, and Reasec.
- "Lomotil- diphenoxylate hydrochloride and atropine sulfate tablet". DailyMed. U.S. National Library of Medicine. 25 October 2021. Retrieved 20 February 2022.
- British National Formulary (76th ed.). Pharmaceutical Press. 2018. p. 66. ISBN 9780857113382.
- Jain M, Wylie WP (June 2021). "Diphenoxylate and Atropine". StatPerls. Treasure Island (FL): StatPearls Publishing. PMID 32644726.
- "Diphenoxylate hydrochloride and atropine sulfate solution". DailyMed. U.S. National Library of Medicine. Retrieved 22 March 2019.
- "Diphenoxylate and Atropine (Professional Patient Advice)". Drugs.com. Retrieved 22 March 2019.
- "Atropine / diphenoxylate Pregnancy and Breastfeeding Warnings". Drugs.com. Retrieved 3 March 2019.
- "Atropine; Diphenoxylate - Drug Usage Statistics". ClinCalc. Retrieved 7 December 2021.
- Rio V (15 August 2019). "Lomotil (diphenoxylate/atropine)". Medical News Today. Archived from the original on 28 September 2020.
- "Lomotil". RxList. Archived from the original on 28 October 2008.
- "Diphenoxylate and atropine drug information". UpToDate. Retrieved 14 February 2017.
- Jain M, Wylie WP (2023). "Diphenoxylate and Atropine". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 32644726. Retrieved 23 June 2023.
- "Memorandum for the Secretary of Defense" (PDF). Archived (PDF) from the original on 16 September 2017. Retrieved 28 July 2013.
- "Diphenoxylate international brands". Drugs.com. Retrieved 11 May 2018.
- DEA, Title 21, Section 829
- "Atropine sulfate mixture with diphenoxylate hydrochloride". Drug Information Portal. U.S. National Library of Medicine.