Why is Lomotil (diphenoxylate) a controlled substance?

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From the Guidelines

Lomotil is a controlled substance because it contains diphenoxylate, an opioid medication that can potentially be abused and cause physical dependence. This classification is due to its potential for abuse, despite the addition of atropine to discourage misuse 1. The combination of diphenoxylate and atropine in Lomotil is designed to treat diarrhea, but the diphenoxylate component can produce mild euphoric effects similar to other opioids, especially at higher-than-prescribed doses. Some key points to consider when prescribing Lomotil include:

  • The potential for physical dependence with prolonged use
  • The risk of abuse, particularly at higher doses
  • The importance of proper prescribing and dispensing practices to minimize these risks
  • The need for patients to be aware of the potential risks and to use Lomotil only as directed by a healthcare provider It's worth noting that alternative treatments, such as loperamide, are available and may be preferred due to their lower potential for abuse and dependence 1. However, Lomotil remains a controlled substance due to its potential for abuse and dependence, and its use should be carefully monitored and managed by healthcare providers.

From the FDA Drug Label

DRUG ABUSE AND DEPENDENCE Controlled Substance Diphenoxylate hydrochloride and atropine sulfate tablets are classified as a Schedule V controlled substance. Diphenoxylate hydrochloride is chemically related to the narcotic analgesic meperidine.

Lomotil is a controlled substance because it contains diphenoxylate hydrochloride, which is:

  • Chemically related to the narcotic analgesic meperidine
  • Classified as a Schedule V controlled substance
  • Can produce opiate withdrawal symptoms at high doses 2
  • Has the potential for addiction at high doses 2

From the Research

Reasons for Lomotil being a Controlled Substance

  • Lomotil, which contains diphenoxylate, has the potential for abuse due to its opioid component 3
  • The presence of diphenoxylate in Lomotil can lead to dependence, as seen in a study of 41 patients who presented with dependence on the medication as their primary substance of abuse 3
  • Regulatory controls are necessary to prevent the escalation of misuse of Lomotil, which is easily available as a prescription drug 3

Comparison with Other Antidiarrheal Agents

  • Loperamide, another antidiarrheal agent, has been found to be safe and effective, with few adverse reactions reported and a lack of significant abuse potential 4
  • Diphenoxylate, the active ingredient in Lomotil, has been compared to loperamide in a double-blind crossover study, which found loperamide to be superior in controlling chronic diarrhea 5

Use in Specific Patient Populations

  • Antimotility agents, including diphenoxylate, have been used to treat chronic diarrhea in people with HIV/AIDS, although there is limited evidence to support their effectiveness in this population 6
  • Loperamide is currently used to treat diarrhea-predominant irritable bowel syndrome (IBS-D), and emerging therapies such as eluxadoline and rifaximin may also be beneficial in this condition 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Lomotil (diphenoxylate) dependence in India.

Indian journal of psychological medicine, 2013

Research

Safety and efficacy of loperamide.

The American journal of medicine, 1990

Research

Antimotility agents for chronic diarrhoea in people with HIV/AIDS.

The Cochrane database of systematic reviews, 2008

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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