What are the guidelines for using racecadotril (enkephalinase inhibitor) in pediatric patients with acute diarrhea?

Racecadotril in Pediatric Acute Diarrhea

Racecadotril is not available in North America (United States and Canada) and should not be considered part of standard management for pediatric acute diarrhea, where oral rehydration therapy remains the cornerstone of treatment. 1, 2

Geographic Availability and Regulatory Status

• Racecadotril is unavailable in the United States and Canada, limiting its practical application in North American pediatric practice 2
• The drug is available in some European, Latin American, and Asian countries where it may be used as an adjunct to oral rehydration therapy 2

Mechanism and Safety Profile

• Racecadotril works through antisecretory mechanisms (enkephalinase inhibition) rather than slowing gut motility, making it theoretically safer than antimotility drugs like loperamide 2
• Unlike loperamide, which is absolutely contraindicated in all children <18 years of age due to risks of respiratory depression and serious cardiac adverse reactions, racecadotril does not share these contraindications 1, 3
• The drug appears to be well-tolerated with mostly mild and transient adverse effects when they occur 4, 5

Evidence for Efficacy

Stool Output Reduction

• Individual trials show racecadotril reduces 48-hour stool output by approximately 46-50% compared to placebo (92 g/kg vs 170 g/kg in one study, P<0.001) 4, 6
• This reduction in stool output translates to decreased oral rehydration solution requirements 4

Duration of Diarrhea

• Some studies report median duration reduction from 72 hours (placebo) to 28 hours (racecadotril) 4
• A 2016 systematic review concluded racecadotril probably reduces the duration of acute diarrhea in pediatric patients 7

Overall Clinical Benefit

• However, the most comprehensive 2019 Cochrane review of 7 RCTs with 1,140 participants concluded that racecadotril has little benefit in improving acute diarrhea in children under five years of age and does not support routine use outside of placebo-controlled trials 5
• The Cochrane review found insufficient evidence to reach conclusions about duration of diarrhea and number of stools in the first 48 hours 5

Dosing (Where Available)

• The standard dose is 1.5 mg/kg administered orally every 8 hours (three times daily) 4, 6
• Always used as adjunct to oral rehydration therapy, never as monotherapy 4, 6

Clinical Recommendation

In regions where racecadotril is available, it may be considered as an adjunct to oral rehydration therapy in children 3 months to 5 years of age with acute watery diarrhea, but it should not replace standard rehydration protocols and offers only modest clinical benefit. 2, 5

Standard of Care Remains Unchanged

• Oral rehydration therapy with reduced osmolarity ORS remains the cornerstone of treatment regardless of racecadotril availability 1
• Administer 50 ml/kg ORS over 2-4 hours for mild dehydration (3-5% deficit) 1, 3
• Administer 100 ml/kg ORS over 2-4 hours for moderate dehydration (6-9% deficit) 1, 3
• Immediate IV rehydration with 20 mL/kg boluses of isotonic fluids for severe dehydration (≥10% deficit) until stabilized, then transition to ORS 1, 3

Key Caveats

• Racecadotril does not reduce the risk of rehydration failure meaningfully (RR 0.41,95% CI 0.13 to 1.23) 5
• Length of hospital stay is not significantly affected 5
• The drug should never delay or replace appropriate rehydration therapy 1, 2
• Continue breastfeeding and resume age-appropriate diet immediately upon rehydration regardless of any adjunctive therapy 1, 3