Loperamide is a synthetic piperidine derivative, classified as an opioid-receptor agonist, used as an antidiarrheal agent. It acts primarily on the μ-opioid receptors in the myenteric plexus of the large intestine, decreasing peristalsis and increasing intestinal transit time. It also enhances anal sphincter tone and reduces fecal volume while increasing viscosity. In the Indian context, it is a widely available, first-line OTC and prescription medication for acute, non-specific diarrhea, but its use in infectious diarrhea is cautioned due to risk of prolonging infection.
Adult: Acute Diarrhea: Initial dose 4 mg (two 2 mg capsules/tablets), followed by 2 mg after each unformed stool. Maximum: 16 mg per day. Chronic Diarrhea: Individualized maintenance dose, typically 4-8 mg/day in divided doses.
Note: Administer orally with or without food. Capsules/Tablets should be swallowed whole with water. Do not crush or chew. For liquid formulations, use the measuring device provided. Maintain adequate hydration (ORS solution) during acute diarrhea.
Loperamide binds to opioid receptors (primarily μ-type) on the circular and longitudinal muscles of the intestinal wall. This activates G-proteins, inhibiting presynaptic acetylcholine and substance P release. The net effect is a decrease in peristaltic activity, prolongation of gastrointestinal transit time, enhancement of intestinal water and electrolyte absorption, and increased anal sphincter tone.
Pregnancy: Category B2 (Australian) / Category C (US FDA). Animal studies show no risk, but human data inadequate. Use only if clearly needed and benefit outweighs risk. Avoid in first trimester unless essential.
Driving: May cause dizziness or drowsiness. Patients should not drive or operate machinery if affected.
| Ketoconazole, Itraconazole, Ritonavir | Potent CYP3A4/P-gp inhibitors. Increase loperamide plasma levels, risk of toxicity (CNS effects, cardiac arrhythmias). | Major |
| Quinidine, Amiodarone, Sotalol | QT prolonging agents. Additive risk of life-threatening cardiac arrhythmias. | Major |
| Opioid Analgesics (e.g., Codeine, Morphine) | Additive constipating effect and CNS depression. | Moderate |
| Anticholinergics (e.g., Atropine, Dicyclomine) | Additive anticholinergic side effects (dry mouth, urinary retention). | Moderate |
| Saquinavir, Nelfinavir (Protease Inhibitors) | Inhibit CYP3A4, increase loperamide levels. | Moderate |
| Rifampicin | Potent CYP3A4 inducer. May decrease loperamide efficacy. | Moderate |