What is the appropriate dosing, contraindications, and use of racecadotril as an adjunct to oral rehydration for acute watery diarrhea in children and adults?

Racecadotril Use in Acute Watery Diarrhea

Racecadotril can be given as an adjunct to oral rehydration therapy in children ≥3 months and adults with acute watery diarrhea, but only in regions where it is available—it is not marketed in the United States or Canada—and current evidence shows only modest clinical benefit that does not justify routine use. 1

Geographic Availability: The Critical Limitation

• Racecadotril is not available in North America, which eliminates its practical application in the United States and Canada. 1
• The drug is marketed in Europe, Latin America, and parts of Asia, so clinicians in those regions may consider its use. 1

Dosing Recommendations

Pediatric Dosing

• Administer 1.5 mg/kg orally every 8 hours (three times daily) in children ≥3 months of age. 1, 2, 3
• Racecadotril should be used only after adequate oral rehydration therapy has been established—never as a substitute for ORS. 1
• Treatment duration typically ranges from 3–5 days or until diarrhea resolves. 2, 3

Adult Dosing

• Clinical trials demonstrate efficacy in adults with acute watery diarrhea, though pediatric-focused guidelines do not specify an adult regimen. 1
• Based on available adult studies, the typical dose is 100 mg three times daily. 1

When to Consider Racecadotril

Use racecadotril when ALL of the following criteria are met:

• The patient has acute watery diarrhea (not bloody, not inflammatory). 1
• Adequate oral rehydration has been initiated and is ongoing. 1
• The patient is ≥3 months of age. 1
• The drug is available in your geographic region. 1
• You have ruled out conditions requiring antimicrobial therapy (see below). 1

Absolute Contraindications

Do NOT use racecadotril when:

• The patient has inflammatory or bloody diarrhea with fever—these cases require diagnostic workup and possible antimicrobial therapy. 1
• Adequate oral rehydration has not been established—ORS is the cornerstone of treatment and must come first. 1, 4
• You are practicing in North America where the drug is unavailable. 1
• The patient is <3 months of age. 1

Evidence of Efficacy: Modest Benefit Only

• A 2019 Cochrane systematic review of 7 RCTs (1,140 children) found that racecadotril may reduce the risk of rehydration failure (RR 0.41,95% CI 0.13–1.23), but the evidence is low-certainty and insufficient to support routine use. 5
• Individual trials show racecadotril reduces stool output by approximately 46–50% in the first 48 hours compared to placebo. 2, 3, 6
• However, the clinical significance of this reduction is modest, and the Cochrane review concluded that racecadotril "has little benefit in improving acute diarrhoea in children under five years of age." 5
• The IDSA guidelines note that while racecadotril can lower stool output, its unavailability in North America and limited clinical benefit prevent any formal recommendation for routine use. 1

Safety Profile: Favorable Compared to Loperamide

• Racecadotril is an antisecretory agent that does not affect intestinal motility, giving it a more favorable safety profile than antimotility drugs like loperamide. 1
• Adverse events in clinical trials were mild and transient, with no significant difference in overall adverse event rates compared to placebo (RR 0.90,95% CI 0.66–1.22). 5, 3
• Loperamide must never be used in children <18 years due to serious adverse events including ileus and death. 7, 1, 4

Critical Clinical Cautions

Do Not Delay Necessary Diagnostics or Antimicrobial Therapy

• Racecadotril is only an adjunct—it must not postpone timely evaluation for signs of inflammatory or invasive diarrhea. 1
• Obtain stool cultures and initiate appropriate antimicrobial therapy when indicated by:
  • Bloody diarrhea with fever and systemic toxicity (suggesting Shigella, Salmonella, enterohemorrhagic E. coli). 7, 1
  • Immunocompromised patients with severe illness. 7
  • Clinical features of sepsis or enteric fever. 7

Oral Rehydration Remains the Priority

• Reduced-osmolarity ORS is the first-line therapy for mild-to-moderate dehydration and must be initiated immediately. 7, 4
• Racecadotril provides no benefit if adequate rehydration is not maintained. 1
• Resume age-appropriate diet during or immediately after rehydration—do not withhold food. 7, 4

Guideline Stance: Limited Recommendation

• The IDSA 2017 guidelines acknowledge racecadotril's ability to reduce stool output but do not recommend it for routine use due to limited-to-moderate quality evidence and unavailability in North America. 1
• The Cochrane 2019 review explicitly states that "current evidence does not support routine use of racecadotril in management of acute diarrhoea in children under five outside of the context of placebo controlled RCTs." 5

Practical Algorithm for Decision-Making

1. Assess hydration status and initiate ORS immediately for mild-to-moderate dehydration. 7, 4
2. Rule out inflammatory/bloody diarrhea requiring antimicrobial therapy. 7, 1
3. Confirm geographic availability of racecadotril (not available in US/Canada). 1
4. If all criteria are met (watery diarrhea, adequate ORS, ≥3 months age, drug available), consider racecadotril 1.5 mg/kg PO every 8 hours as adjunct therapy. 1, 2, 3
5. Continue ORS and age-appropriate diet throughout treatment. 7, 4
6. Monitor for red flags (bloody stools, high fever, altered mental status) requiring escalation of care. 7, 1, 4

Common Pitfalls to Avoid

• Do not use racecadotril as a substitute for ORS—rehydration is the cornerstone of treatment. 1, 4
• Do not prescribe racecadotril in North America—it is not available. 1
• Do not use racecadotril in inflammatory or bloody diarrhea—these cases require diagnostic workup and possible antibiotics. 1
• Do not delay antimicrobial therapy in patients with fever, bloody stools, or systemic toxicity while waiting to see if racecadotril works. 1
• Do not confuse racecadotril with loperamide—loperamide is contraindicated in children <18 years and in any patient with fever or bloody diarrhea. 7, 1, 4