LOMOTIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LOMOTIL (LOMOTIL).
Diphenoxylate is a meperidine congener that acts as an opioid receptor agonist, inhibiting gastrointestinal motility and prolonging transit time; atropine is added to discourage abuse at high doses.
| Metabolism | Diphenoxylate is metabolized primarily by the liver to diphenoxylic acid (active metabolite); CYP enzymes involved (mainly CYP3A4). |
| Excretion | Primarily renal (50-70% as metabolites, <5% unchanged) and fecal (30-50% via biliary excretion). |
| Half-life | Diphenoxylate: 2.5-3.5 hours; Difenoxin (active metabolite): 12-24 hours. Clinically, antidiarrheal effect is prolonged due to metabolite accumulation. |
| Protein binding | 90% (diphenoxylate) and 80% (difenoxin) bound primarily to albumin. |
| Volume of Distribution | Diphenoxylate: 3.0-5.0 L/kg; difenoxin: 2.5-4.0 L/kg. Indicates extensive tissue distribution. |
| Bioavailability | Oral: approximately 90% (first-pass metabolism to difenoxin). |
| Onset of Action | Oral: 30-60 minutes for clinical effect. |
| Duration of Action | Oral: 3-4 hours for diphenoxylate; up to 24 hours for metabolite effects. Clinical notes: Duration is extended with repeated dosing due to active metabolite. |
| Molecular Weight | 452.55 |
| Brand Substitutes | Phenotil Tablet |
Adults: 2 tablets (2.5 mg diphenoxylate/0.025 mg atropine) orally four times daily until control of diarrhea is achieved; maintenance dose is 2 tablets once or twice daily. Maximum dose: 8 tablets (20 mg diphenoxylate) per day.
| Dosage form | TABLET |
| Renal impairment | Not studied. Use with caution due to potential accumulation of active metabolites. No specific GFR-based dosing recommendations; avoid in severe renal impairment. |
| Liver impairment | Child-Pugh A: No adjustment; dose cautiously. Child-Pugh B: Reduce dose by 50% or avoid. Child-Pugh C: Do not use. |
| Pediatric use | Children 2-12 years: Use oral solution (0.25 mg diphenoxylate/mL). Dose: 0.3-0.4 mg/kg of diphenoxylate orally per day in 4 divided doses. Maximum: 4 mL (1 mg diphenoxylate) per dose for 2-5 years; 6 mL (1.5 mg) per dose for 5-8 years; 8 mL (2 mg) per dose for 8-12 years. Not recommended for children <2 years. |
| Geriatric use | Initiate at lower doses (e.g., 2 tablets once daily) due to increased sensitivity to anticholinergic effects (atropine), risk of dehydration, and potential for central nervous system toxicity. Titrate cautiously; avoid prolonged use. |
| 1st trimester | Risk of congenital malformations based on limited human data. Avoid use unless benefit outweighs risk. |
| 2nd trimester | Use only if clearly needed; potential for fetal effects based on animal studies. |
| 3rd trimester | Avoid due to risk of neonatal respiratory depression and withdrawal symptoms. |
Clinical note
Comprehensive clinical and safety monograph for LOMOTIL (LOMOTIL).
| Placental transfer | Diphenoxylate and difenoxin cross the placenta; evidence from animal studies and limited human data. |
| Breastfeeding | Diphenoxylate and its active metabolite (difenoxin) are excreted into breast milk in small amounts. Monitor infant for sedation, respiratory depression, and constipation. Use with caution, especially in preterm infants or those with glucose-6-phosphate dehydrogenase deficiency. |
■ FDA Black Box Warning
Risk of respiratory depression, especially in children; not recommended in children younger than 6 years. Concomitant use with alcohol or CNS depressants may increase risk.
| Serious Effects |
Hypersensitivity to diphenoxylate or atropineChildren under 6 years of ageObstructive jaundiceSevere hepatic impairmentAcute diarrhea associated with pseudomembranous colitis or enterotoxin-producing bacteriaGlaucomaMyasthenia gravis
| Precautions | May cause respiratory depression, particularly at high doses or in children, Risk of anticholinergic effects from atropine component, Potential for abuse and dependence, Use with caution in patients with hepatic impairment, May precipitate toxic megacolon in patients with acute colitis, Discontinue if ileus or abdominal distention develops |
| Food/Dietary | No specific food interactions reported. However, avoid grapefruit juice as it may theoretically affect metabolism via CYP3A4 inhibition (diphenoxylate is metabolized by CYP3A4). Maintain adequate fluid intake to prevent dehydration. Avoid alcohol during therapy. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited data; diphenoxylate and atropine are not associated with major malformations in animal studies, but human data are insufficient. Second and third trimesters: No evidence of fetal harm, but prolonged use may cause neonatal withdrawal or anticholinergic effects. Use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal vital signs and signs of anticholinergic toxicity (tachycardia, dry mouth, urinary retention). For fetus, monitor growth and amniotic fluid volume with prolonged use. Observe neonate for withdrawal symptoms if used near term. |
| Fertility Effects | No known negative impact on fertility in animal or human studies. Anticholinergic effects may theoretically affect sperm motility, but clinical significance is unestablished. |
| Clinical Pearls | Lomotil (diphenoxylate/atropine) is an antidiarrheal with opioid agonist activity; use cautiously in patients with inflammatory bowel disease due to risk of toxic megacolon. Avoid in children under 6 years. Monitor for CNS depression, especially in combination with other CNS depressants. Atropine component may cause anticholinergic effects (dry mouth, blurred vision, urinary retention). Onset is rapid, but avoid exceeding recommended doses; may cause physical dependence with prolonged use. |
| Patient Advice | Take exactly as prescribed; do not exceed the recommended dose. · Do not use for more than 2 days unless directed by a doctor. · Avoid alcohol and other CNS depressants (e.g., sedatives, tranquilizers) as they may increase drowsiness and dizziness. · Drink plenty of clear fluids to prevent dehydration caused by diarrhea. · Contact your healthcare provider if diarrhea persists for more than 2 days or if you develop a fever or blood in stool. · This medication may cause dry mouth, blurred vision, or constipation; report any severe or persistent symptoms. · Keep out of reach of children; accidental overdose can cause severe respiratory depression. · Do not use if you have a history of glaucoma, enlarged prostate, or liver disease without consulting your doctor. |