Has Lomotil (diphenoxylate/atropine) ever been classified as a controlled substance?

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Lomotil (Diphenoxylate/Atropine) Controlled Substance Status

Yes, Lomotil has been classified as a Schedule V controlled substance since its approval, and remains so today. 1

Current DEA Classification

Diphenoxylate hydrochloride (the active opioid component of Lomotil) is classified as a Schedule V controlled substance under the Controlled Substances Act. 1 This classification reflects the drug's potential for abuse and dependence, albeit lower than Schedule II-IV substances.

Rationale for Controlled Status

The FDA drug label explicitly states that diphenoxylate is "chemically related to the narcotic analgesic meperidine" and possesses opioid properties. 1 Several factors justify its controlled status:

  • At therapeutic doses (used for diarrhea), diphenoxylate does not produce morphine-like subjective effects or addiction. 1

  • At high doses (100-300 mg/day, equivalent to 40-120 tablets), diphenoxylate exhibits codeine-like subjective effects and can produce opiate withdrawal symptoms when discontinued after 40-70 days of use. 1

  • The insolubility of diphenoxylate in aqueous media prevents intravenous self-administration, which reduces but does not eliminate abuse potential. 1

Comparison to Other Antidiarrheal Agents

Unlike loperamide (Imodium), which is available over-the-counter and is not a controlled substance, Lomotil requires a prescription specifically because of its greater potential for central nervous system effects and abuse. 2 The addition of atropine to the diphenoxylate formulation was intended as a deterrent to abuse by causing unpleasant anticholinergic side effects at supratherapeutic doses. 1

Clinical Implications of Controlled Status

  • Prescribers must follow DEA regulations when prescribing Lomotil, including limitations on refills and proper documentation. 1

  • The recommended dosage should not be exceeded, as addiction to diphenoxylate is possible at high doses. 1

  • Lomotil is generally considered inferior to loperamide for acute diarrhea due to more problematic side effects and its controlled status. 2

Historical Context

The controlled substance classification has been in place since the drug's approval in 1959. 3 This early classification reflects recognition of diphenoxylate's opioid structure and pharmacology, even though the therapeutic dose is "widely separated from the dose which causes central nervous system effects." 1

References

2
Guideline

Mechanism of Action and Clinical Effects of Lomotil and Loperamide

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

3
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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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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