MOTOFEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MOTOFEN (MOTOFEN).
Combination of diphenoxylate (opioid agonist) and atropine (anticholinergic). Diphenoxylate acts on μ-opioid receptors in the gut to slow peristalsis and reduce fluid secretion; atropine is added to discourage abuse by causing unpleasant anticholinergic effects at high doses.
| Metabolism | Diphenoxylate is extensively metabolized via ester hydrolysis to diphenoxylic acid (active metabolite) and further conjugated; CYP3A4 and other CYP enzymes may be involved. Atropine is metabolized via hepatic enzymes including CYP2D6. |
| Excretion | Renal: ~60%; Fecal/Biliary: ~40% |
| Half-life | Terminal elimination half-life: 20-24 hours; clinical context: once-daily dosing recommended |
| Protein binding | ~95%; primarily bound to albumin |
| Volume of Distribution | 3-5 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: ~60% (first-pass metabolism reduces systemic availability) |
| Onset of Action | Oral: 30-60 minutes |
| Duration of Action | 6-8 hours; clinical note: antidiarrheal effect may persist longer in some patients |
| Molecular Weight | 344.88 |
1 to 2 tablets orally every 6 hours as needed, not to exceed 8 tablets per day.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in severe renal impairment (GFR <30 mL/min). No adjustment required for mild to moderate impairment (GFR 30-89 mL/min). |
| Liver impairment | Contraindicated in Child-Pugh class C cirrhosis. Use with caution in Child-Pugh class A or B; reduce dose by 50% or extend dosing interval. |
| Pediatric use | Not recommended for children under 12 years. For children 12 years and older, same as adult dosing. |
| Geriatric use | Initiate at lower dose (1 tablet every 8 hours) due to increased sensitivity to anticholinergic effects and potential for prolonged QT interval. |
| 1st trimester | Limited human data; animal studies suggest risk. Generally avoided due to potential teratogenic effects. |
| 2nd trimester | Avoid use; may cause neonatal respiratory depression and withdrawal symptoms. |
| 3rd trimester | Avoid use; high risk of neonatal respiratory depression, hypotonia, and withdrawal. |
Clinical note
Comprehensive clinical and safety monograph for MOTOFEN (MOTOFEN).
| Placental transfer | Crosses placenta; distributed to fetal tissues. |
| Breastfeeding | Excreted into breast milk in low concentrations. However, due to risk of sedation and respiratory depression in the infant, use is not recommended. |
| Lactation Rating |
■ FDA Black Box Warning
Not FDA-approved for use in children under 6 years due to risk of respiratory depression and anticholinergic toxicity.
| Serious Effects |
Hypersensitivity to diphenoxylate or atropineObstructive jaundiceDiarrhea associated with pseudomembranous enterocolitis or enterotoxin-producing bacteriaChildren under 2 years of age
| Precautions | Respiratory depression (especially in children), anticholinergic effects (tachycardia, urinary retention, dry skin, blurred vision), hepatotoxicity, risk of toxic megacolon in inflammatory bowel disease, drug dependence with prolonged use. |
| Food/Dietary | No significant food interactions. Avoid alcohol due to additive CNS depression. |
Loading safety data…
| L4 |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no teratogenicity at therapeutic doses; theoretical risk of anticholinergic effects on fetal development. Second/Third trimester: No known teratogenicity; potential for fetal anticholinergic effects (tachycardia, decreased GI motility) with high maternal doses; avoid near term due to possible neonatal anticholinergic syndrome. |
| Fetal Monitoring | Monitor maternal heart rate, blood pressure, and bowel function; fetal heart rate monitoring if high doses used; ultrasound for fetal growth if prolonged use. |
| Fertility Effects | No known adverse effects on human fertility; animal studies show no impairment of fertility at therapeutic doses. |
| Clinical Pearls |
| Motofen (difenoxin/atropine) is a schedule IV controlled substance; anticholinergic effects from atropine may cause dry mouth, blurred vision, and urinary retention; use with caution in patients with glaucoma, myasthenia gravis, or hepatic impairment; not recommended in children under 6 years; avoid use in acute diarrhea due to infectious colitis (e.g., C. difficile) due to risk of toxic megacolon. |
| Patient Advice | Take exactly as prescribed; do not exceed recommended dose. · Do not take for more than 2 days; see doctor if diarrhea persists. · May cause drowsiness or dizziness; avoid driving or operating machinery. · Avoid alcohol and other CNS depressants. · Report severe constipation, abdominal pain, or bloody stools immediately. · Keep out of reach of children; this medication can cause severe breathing problems in children. |