Antidiarrhoeal Drugs

Antidiarrhoeal drugs reduce stool volume and frequency by slowing transit, reducing secretion or binding fluid, bile acids or toxins. Oral rehydration remains the treatment that prevents death in acute diarrhoea.

Classification. Opioid receptor agonists (loperamide, codeine, diphenoxylate), enkephalinase inhibitors (racecadotril), bismuth salts, bile acid sequestrants, somatostatin analogues, and zinc.

• Low-osmolarity oral rehydration solution (sodium 75 mmol/L, glucose 75 mmol/L, 245 mOsm/L): children under 2 years 50 to 100 mL and children 2 to 10 years 100 to 200 mL after each loose stool; older patients as desired.
• Zinc 20 mg daily for 10 to 14 days in children over 6 months; 10 mg daily under 6 months.
• Loperamide 4 mg initially, then 2 mg after each loose stool; maximum 16 mg daily.
• Racecadotril 100 mg three times daily in adults.
• Codeine phosphate 30 mg up to four times daily.
• Cholestyramine 4 g once to four times daily for bile acid diarrhoea.
• Octreotide for refractory high-output diarrhoea, under specialist direction.

Differences. Loperamide does not cross the blood-brain barrier at usual doses. Codeine is sedating and constipating.

• Acute watery diarrhoea: oral rehydration first; loperamide for adults without fever or blood; zinc in children.
• Cholera: aggressive rehydration with oral or intravenous fluids, and a single antibiotic dose in severe disease (doxycycline 300 mg or azithromycin 1 g in adults); antimotility drugs are not advised.
• Chronic functional diarrhoea: loperamide as needed.
• Bile acid diarrhoea: cholestyramine.
• Short bowel and high-output stoma: loperamide up to 16 mg daily, codeine, then octreotide.

Selection. Exclude infection, coeliac disease, inflammatory bowel disease and medicines (metformin, magnesium, laxatives, antibiotics) in chronic diarrhoea.

Contraindications. Loperamide and opioids in bloody diarrhoea, fever, suspected Clostridioides difficile infection, severe colitis, toxic megacolon, ileus, and in children under 12 years (under 2 years absolutely).

Adverse effects. Constipation, bloating and ileus. High-dose loperamide (misuse) causes QT prolongation, torsades de pointes and cardiac arrest. Codeine causes sedation and dependence.

Interactions. Loperamide levels rise with ritonavir, itraconazole, quinidine and gemfibrozil; cholestyramine binds many drugs, so give others 1 hour before or 4 to 6 hours after.

Special groups.

• Pregnancy: loperamide short term acceptable; prioritise rehydration.
• Breastfeeding: loperamide small amounts; acceptable.
• Children: oral rehydration solution and zinc; no antimotility drugs.
• Liver impairment: caution with loperamide.
• Kidney impairment: no adjustment; watch electrolytes.

Monitoring. Hydration status, urine output, sodium and potassium, stool frequency, and ECG with high-dose loperamide.

Referral and escalation. Admit severe dehydration, blood in stool with fever, diarrhoea over 14 days, immunosuppression (including advanced HIV), recent antibiotics with colitis, or age under 6 months.