1. Clinical Overview
Racecadotril is a peripherally-acting, selective enkephalinase inhibitor used as an antisecretory antidiarrheal agent. It acts locally in the intestinal mucosa to reduce hypersecretion of water and electrolytes without affecting intestinal motility or transit time, making it distinct from opioids like loperamide. It is a prodrug, hydrolyzed to its active metabolite thiorphan.
| Onset | Duration | Bioavailability |
|---|---|---|
| Within 30 minutes to 1 hour. | Approximately 6 to 8 hours. | Approximately 10% (as the prodrug). The active metabolite, thiorphan, is formed locally in the gut wall. |
2. Mechanism of Action
Racecadotril is a prodrug hydrolyzed to thiorphan, which is a potent and selective inhibitor of membrane-bound enkephalinase (neprilysin). This enzyme degrades endogenous enkephalins in the gastrointestinal tract. By inhibiting enkephalinase, racecadotril increases local concentrations of enkephalins. Enkephalins then activate delta-opioid receptors on enterocytes, which inhibits adenylate cyclase. This reduces intracellular cyclic AMP (cAMP) levels, leading to decreased secretion of water and electrolytes (chloride) into the intestinal lumen.
3. Indications & Uses
- Acute watery diarrhea in adults and children (as an adjunct to Oral Rehydration Solution - ORS).
- Acute secretory diarrhea of various etiologies (viral, bacterial).
4. Dosage & Administration
Adult Dosage: 100 mg (one 100mg capsule/tablet) three times daily. In some Indian brands, 10mg sachets are available for pediatric use; adult dosing uses the 100mg strength.
Administration: Administer orally, preferably before meals. The granules from the sachet should be mixed with a small amount of water, milk, or soft food (like yogurt) and consumed immediately. Do not swallow the granules dry. Capsules/Tablets should be swallowed whole with water. Continue administration until diarrhea stops, usually for a maximum of 7 days. MUST be co-administered with Oral Rehydration Solution (ORS) to prevent dehydration.
5. Side Effects
Common side effects may include:
- Headache (mild).
- Dizziness.
- Constipation (rare, compared to loperamide).
- Nausea.
- Abdominal pain.
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| ACE Inhibitors (e.g., Enalapril, Ramipril) | Theoretical additive risk of angioedema due to dual inhibition of kininase II (ACE) and enkephalinase. Clinical significance is uncertain but caution advised. | Moderate |
| Angiotensin Receptor Blockers (ARBs) | No known pharmacokinetic interaction. Theoretical pharmacodynamic interaction similar to ACE inhibitors is possible but less likely. | Low |
| Opioid Analgesics (e.g., Morphine, Codeine) | No significant pharmacokinetic interaction. However, concurrent use with centrally-acting opioids for diarrhea is not recommended as racecadotril is sufficient. | Low |
| Antibiotics (e.g., Ciprofloxacin, Metronidazole) | No interaction. Often co-prescribed for infectious diarrhea. Racecadotril does not interfere with antibiotic efficacy. | None |
7. Patient Counselling
- DO continue to drink plenty of fluids, especially Oral Rehydration Solution (ORS), to prevent dehydration.
- DO take the medicine as prescribed, usually before meals.
- DO mix the granules from the sachet with water/milk/food; do not swallow dry.
- DO complete the course as advised, but not beyond 7 days unless directed.
- DONT use for diarrhea with high fever or blood in stools without consulting a doctor.
- DONT take with other antidiarrheal medicines (like loperamide) unless prescribed.
- DONT stop ORS while taking this medicine.
8. Toxicology & Storage
Overdose: Limited data. Potential symptoms may include marked constipation, abdominal distension, drowsiness, dizziness, and nausea. Severe overdose could theoretically lead to ileus.
Storage: Store below 30°C in a cool, dry place, protected from light and moisture. Keep the sachets/tablets in the original packaging. Keep out of reach of children.