What is the proper administration and dosing of Lomotil (diphenoxylate hydrochloride with atropine sulfate)?

Lomotil Administration and Dosing

Lomotil (diphenoxylate/atropine) is NOT a first-line agent for diarrhea—loperamide is preferred due to superior efficacy and fewer side effects—but when used, adults receive 5 mg (2 tablets) four times daily initially, then reduced to 5 mg daily as needed, while children ≥2 years receive weight-based dosing with extreme caution. 1, 2

Critical Safety Restrictions

Age Restrictions

• Contraindicated in children under 2 years of age due to risk of serious central and peripheral nervous system effects related to immature hepatic function and blood-brain barrier 2, 3
• Use with special caution in young children due to greater variability of response 3

Absolute Contraindications

• Never use in severe dysentery with high fever or bloody stools—it worsens outcomes and is no more effective than placebo 1, 2
• Avoid in suspected infectious diarrhea caused by invasive organisms (Shigella, Salmonella, STEC) as it may prolong illness and increase complications 1, 4
• Neutropenic patients require careful risk-benefit assessment due to risk of iatrogenic ileus and bacteremia 2

Adult Dosing

Oral Administration

• Initial dose: 5 mg (2 tablets) four times daily 3
• Maintenance: Reduce to 5 mg once daily or as needed after symptoms are controlled 3
• Maximum: Do not exceed recommended dosage—addiction is possible at 100-300 mg/day (40-120 tablets) 3

Pediatric Dosing (≥2 years only)

Weight-Based Dosing

• Use liquid formulation for precise dosing in children 3
• Dosing should be accompanied by appropriate fluid and electrolyte therapy 3
• Exercise extreme caution due to high risk of toxicity—respiratory depression is the most threatening reaction and may occur with delayed onset 5

Clinical Context for Use

Positioning in Treatment Algorithm

• First-line: Loperamide is recommended as initial therapy 1
• Second-line: Consider Lomotil only when loperamide is ineffective or contraindicated 1, 2
• Third-line in cancer patients: After loperamide and octreotide have failed, and only after excluding infectious causes 1, 2

Required Precautions

• Always exclude infectious diarrhea before initiating therapy 1, 2
• Monitor for signs of toxic megacolon or ileus 2
• Avoid concurrent use with MAO inhibitors, barbiturates, tranquilizers, and alcohol 3
• Diphenoxylate inhibits hepatic microsomal enzymes and may prolong half-lives of other drugs 3

Special Populations

Pregnancy and Lactation

• Pregnancy Category C: Use only if benefit justifies potential fetal risk 3
• Nursing mothers: Exercise caution—diphenoxylic acid and atropine are secreted in breast milk 3

Abuse Potential Warning

• Classified as Schedule V controlled substance 3
• At therapeutic doses, lacks morphine-like subjective effects, but exhibits codeine-like effects at high doses 3
• Reports of dependence exist, particularly in patients with opioid use history 6

Common Pitfall

The most dangerous error is using Lomotil in infectious diarrhea, particularly Shiga dysentery, which can result in prolonged toxic illness lasting months to years despite appropriate antibiotic therapy 4. Always rule out invasive bacterial pathogens before prescribing.