What is the recommended adult dosing for Lomotil (diphenoxylate hydrochloride with atropine sulfate)?

Lomotil Adult Dosing

For adults with acute diarrhea, the FDA-approved initial dose of Lomotil is 5 mg (two 2.5 mg tablets) four times daily until diarrhea is controlled, followed by dose reduction; however, loperamide is strongly preferred as first-line therapy due to superior efficacy and safety profile. 1

FDA-Approved Adult Dosing

Initial Dose:

• 5 mg (two 2.5 mg tablets) orally four times daily until diarrhea is initially controlled 1
• This translates to 20 mg total daily dose during the acute phase 1

Maintenance Dose:

• After initial control, reduce to as little as 5 mg (two tablets) daily as needed 1
• Do not exceed the recommended dosage due to risk of respiratory depression, coma, and potential for dependence at high doses 1

Critical Clinical Context

Lomotil is NOT first-line therapy:

• The American Gastroenterological Association recommends loperamide over Lomotil because it is more effective with fewer central nervous system effects 2, 3
• Lomotil should only be considered when loperamide is ineffective or contraindicated 2, 4
• In cancer patients with chemotherapy-induced diarrhea, Lomotil is a third-line option after loperamide and octreotide 2

Absolute Contraindications

Never use Lomotil in:

• Severe dysentery with high fever or bloody stools 2, 4
• Suspected infectious diarrhea from invasive organisms (Shigella, Salmonella, STEC) 2, 4
• Children under 2 years of age 4, 1

Important Safety Warnings

Abuse Potential:

• Lomotil is a Schedule V controlled substance due to the opioid component (diphenoxylate) 1
• At doses of 100-300 mg/day (40-120 tablets), opiate withdrawal symptoms occur 1
• Requires prescription due to potential for central nervous system effects 3

Drug Interactions:

• Potentiates effects of alcohol, barbiturates, and tranquilizers 1
• May interact with MAO inhibitors 1
• Can inhibit hepatic microsomal enzymes, potentially prolonging half-lives of other medications 1

Atropine-Related Effects:

• The subtherapeutic dose of atropine added to prevent abuse can cause atropinism, particularly in children with Down syndrome 1
• Patients should be cautioned about drowsiness, dizziness, and impaired ability to operate machinery 1

Neutropenic Patients:

• Require careful risk-benefit assessment, as overdosage may cause iatrogenic ileus with increased bacteremia risk 4

Clinical Pitfalls to Avoid

• Do not use in infectious diarrhea: Antimotility agents can worsen outcomes and prolong illness, particularly with Shigella dysenteriae 4, 5
• Do not exceed recommended doses: Risk of severe respiratory depression, coma, and permanent brain damage 1
• Keep out of reach of children: Accidental pediatric ingestion can be fatal 1
• Exclude infection first: In cancer patients or immunocompromised individuals, always rule out infectious causes before initiating therapy 2, 4