Racecadotril – Mechanism, Dosage & Uses

What is Racecadotril?

Racecadotril is an antidiarrhoeal agent used in the treatment of acute diarrhoea. It belongs to the class of enkephalinase inhibitors (also known as neprilysin inhibitors) and acts locally within the gastrointestinal tract without affecting the central nervous system. The drug is approved in many countries for use in infants, children, and adults, and is frequently used alongside oral rehydration therapy.

Indications

Racecadotril is indicated for:

• Acute secretory diarrhoea in infants, toddlers, and children
• Acute diarrhoea in adults requiring symptomatic relief
• Diarrhoea of infectious or non-infectious origin

Mechanism of Action

Racecadotril is a prodrug: after oral ingestion, it is converted in the body into its active metabolite thiorphan. Thiorphan inhibits the enzyme enkephalinase (neprilysin), which normally breaks down naturally occurring pain- and secretion-regulating peptides known as enkephalins.

By inhibiting enkephalinase, enkephalins remain active for longer and can exert their effects at the delta-opioid receptors of the intestinal mucosa. This results in:

• Reduced secretion of water and electrolytes into the intestinal lumen (antisecretory effect)
• Normalisation of intestinal motility without completely suppressing it

Unlike loperamide, racecadotril has minimal effect on gut motility, which means the risk of bloating caused by trapped gas is considerably lower.

Dosage

Dosing of racecadotril depends on the patient's age and body weight:

• Infants and young children: Typically 1.5 mg/kg body weight, three times daily, administered as granules or sachets dissolved in liquid
• Adults: Usually 100 mg, three times daily with meals
• Treatment duration should generally not exceed 7 days or should continue until diarrhoea resolves

Important: Racecadotril does not replace fluid and electrolyte replacement. Oral rehydration therapy remains the cornerstone of diarrhoea management, especially in children.

Side Effects

Racecadotril is generally well tolerated. Known side effects include:

• Headache
• Vomiting
• Skin rash or allergic reactions (rare)
• Constipation (less common than with loperamide)

Serious adverse effects are rare. The medication should not be taken if there is a known hypersensitivity to racecadotril or any of its excipients.

Contraindications and Interactions

Racecadotril should not be used in cases of:

• Hypersensitivity to racecadotril or thiorphan
• Severe hepatic or renal impairment (use with caution)
• Concomitant use of other enkephalinase inhibitors

Drug interactions are rarely reported; however, caution is advised when combining racecadotril with loperamide, as this may result in excessive suppression of intestinal motility.

Clinical Relevance

Racecadotril is particularly valuable in paediatric medicine, as it can significantly reduce the duration of diarrhoea and fluid loss in children without the typical motility-inhibiting side effects associated with other antidiarrhoeal agents. Multiple clinical trials and meta-analyses have confirmed its efficacy and safety in children with acute diarrhoea.

References

1. Lehert P, Chéron G, Calatayud GA, et al. - Racecadotril for childhood gastroenteritis: an individual patient data meta-analysis. Digestive and Liver Disease, 2011; 43(9): 707-713.
2. European Medicines Agency (EMA) - Hidrasec (Racecadotril): Product information and assessment report. Available at: www.ema.europa.eu
3. Szajewska H, Ruszczyński M, Chmielewska A, Wieczorek J - Systematic review: racecadotril in the treatment of acute diarrhoea in children. Alimentary Pharmacology and Therapeutics, 2007; 26(6): 807-813.