Diphenoxylate + Atropine is a fixed-dose combination antidiarrheal agent. Diphenoxylate is a synthetic opioid derivative that acts as a peripheral μ-opioid receptor agonist in the myenteric plexus of the intestinal wall, slowing intestinal motility and fluid secretion. Atropine sulfate is added in a sub-therapeutic dose (1/100th of diphenoxylate) to discourage deliberate abuse and overdose by producing unpleasant anticholinergic side effects at higher doses. It is a Schedule H drug in India, primarily used for the symptomatic management of acute, non-infectious diarrhea.
Adult: Initial: 2 tablets (5 mg diphenoxylate) four times daily. Maintenance: Once diarrhea is controlled, reduce dose to as low as 2 tablets per day. Maximum initial daily dose: 20 mg diphenoxylate (8 tablets).
Note: Take orally with or without food. Do not crush or chew. Swallow whole with a glass of water. Use only for acute episodes; therapy beyond 48-72 hours without medical supervision is not recommended. Must be used as part of rehydration therapy (Oral Rehydration Solution - ORS).
Diphenoxylate acts locally on the μ-opioid receptors in the myenteric plexus of the intestinal wall. This activation inhibits acetylcholine release, leading to decreased peristalsis, increased segmental contractions, and enhanced intestinal transit time. It also promotes absorption of water and electrolytes. Atropine, an antimuscarinic agent, inhibits parasympathetic nervous system activity. In this sub-therapeutic dose, it primarily serves to cause unpleasant side effects (dry mouth, blurred vision) if the tablets are taken in excessive quantities to deter abuse.
Pregnancy: Category C (US FDA). Use only if potential benefit justifies potential risk to the fetus. Not recommended during pregnancy, especially near term (risk of neonatal withdrawal).
Driving: May cause dizziness and drowsiness. Patients should be cautioned against driving or operating machinery until their response is known.
| CNS Depressants (Alcohol, Benzodiazepines, Barbiturates, Opioids) | Additive CNS and respiratory depression. | Major |
| Monoamine Oxidase Inhibitors (MAOIs) - e.g., Phenelzine | Risk of hypertensive crisis (theoretical). | Major |
| Anticholinergic drugs (Tricyclic antidepressants, Antipsychotics, Antihistamines) | Additive anticholinergic side effects (dry mouth, urinary retention, hyperthermia). | Moderate |
| Macrolide antibiotics (Erythromycin, Clarithromycin) | May inhibit metabolism of diphenoxylate, increasing levels and toxicity. | Moderate |
| Protease Inhibitors (Ritonavir) | May increase diphenoxylate levels. | Moderate |
Same composition (Diphenoxylate (2.5mg) + Atropine (0.025mg)), different brands: