1. Clinical Overview
Racecadotril is a peripherally-acting enkephalinase inhibitor used as an antisecretory agent for the symptomatic treatment of acute diarrhea in adults and children. It acts locally in the intestine without affecting intestinal motility, making it a preferred alternative to motility inhibitors like loperamide. It is a prodrug that is rapidly hydrolyzed to its active metabolite, thiorphan.
| Onset | Duration | Bioavailability |
|---|---|---|
| Within 30-60 minutes of oral administration. | Approximately 8 hours. | Approximately 10% (for the active metabolite, thiorphan). |
2. Mechanism of Action
Racecadotril is a prodrug hydrolyzed to thiorphan, which is a potent and selective inhibitor of membrane-bound enkephalinase (neprilysin) located on the brush border of enterocytes. Inhibition of this enzyme prevents the degradation of endogenous enkephalins (like met-enkephalin). Enkephalins then bind to delta-opioid receptors on enterocytes, activating a pertussis toxin-sensitive G-protein. This leads to a reduction in intracellular cyclic AMP and calcium levels, ultimately inhibiting the hypersecretion of water and electrolytes into the intestinal lumen without affecting normal peristalsis.
3. Indications & Uses
- Symptomatic treatment of acute diarrhea in adults
- Symptomatic treatment of acute diarrhea in children (≥3 months of age)
4. Dosage & Administration
Adult Dosage: 30mg (one capsule) three times daily, before main meals. Continue for a maximum of 7 days or until the first normal stool.
Administration: Capsule should be swallowed whole with a glass of water, preferably before meals. For pediatric sachets, mix the granules with a small amount of water, milk, or soft food (like yogurt) and administer immediately. Oral Rehydration Solution (ORS) must be used concurrently to prevent and treat dehydration.
5. Side Effects
Common side effects may include:
- Headache
- Constipation (less common than with loperamide)
- Nausea
- Drowsiness
- Skin rash
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| ACE Inhibitors (e.g., Ramipril, Enalapril) | Theoretical potential for additive inhibition of enkephalinase/bradykinin degradation, potentially increasing risk of angioedema. Clinical significance is uncertain. | Moderate |
| Antihypertensives | Potential additive hypotensive effect (rare). | Low |
| CNS Depressants (Alcohol, Benzodiazepines, Opioids) | May potentiate drowsiness or dizziness. | Low |
| Diuretics | Increased risk of electrolyte imbalance (hyponatremia, hypokalemia) in the context of diarrhea. | Moderate |
7. Patient Counselling
- DO take the capsule with water before meals.
- DO use Oral Rehydration Solution (ORS) liberally to prevent dehydration.
- DO continue breastfeeding or normal feeding in children.
- DO complete the course as advised, but stop after first normal stool if within 7 days.
- DONT use for more than 7 days without consulting a doctor.
- DONT use in children under 3 months of age.
- DONT use if you have high fever or blood in stools without consulting a doctor.
8. Toxicology & Storage
Overdose: Symptoms are an extension of side effects: severe drowsiness, marked constipation, nausea, vomiting, and potential for significant fluid/electrolyte imbalance due to over-correction of diarrhea.
Storage: Store below 30°C in a cool, dry place, protected from light and moisture. Keep out of reach of children. For granules/sachets: use immediately after mixing with liquid/food; do not store the mixture.