When is racecadotril (acetorphan) used in the treatment of acute diarrhea?

When to Use Racecadotril

Racecadotril can be considered as adjunctive therapy to oral rehydration in acute watery diarrhea, particularly in regions where it is available (not North America), but current evidence does not support its routine use as it provides only modest clinical benefit compared to oral rehydration alone. 1, 2

Geographic Availability and Regulatory Context

• Racecadotril is not available in North America, limiting its practical application in the United States and Canada 1
• The drug is available in Europe, Latin America, and parts of Asia where it has been studied and used clinically 3, 4, 5

Mechanism and Clinical Effects

• Racecadotril works as an antisecretory agent by inhibiting neutral endopeptidase (enkephalinase), which reduces pathologic intestinal secretion without affecting gastrointestinal motility or transit time 3
• This distinguishes it fundamentally from antimotility agents like loperamide, making it theoretically safer in inflammatory diarrhea 3
• The drug reduces stool volume by approximately 40-50% when added to oral rehydration therapy 4, 6

Evidence-Based Indications

Children (3 months to 5 years)

• Racecadotril may be used as adjunct to oral rehydration solution in acute diarrhea at a dose of 1.5 mg/kg three times daily 4
• Studies show reduced stool output in the first 48 hours and faster recovery time 4, 5
• However, a 2019 Cochrane review concluded that while racecadotril appears safe, it has little benefit in improving acute diarrhea and does not support routine use outside of research settings 2
• The drug may reduce emergency department revisits during the same diarrheal episode 5

Adults

• Racecadotril has demonstrated efficacy in reducing stool volume in adults with acute diarrhea 1, 3
• It should only be considered after adequate hydration is achieved, as it is not a substitute for fluid and electrolyte therapy 1
• The drug is mentioned in guidelines but without strong recommendations for routine use 1

Clinical Decision Algorithm

Use racecadotril when:

• Patient has acute watery (non-inflammatory) diarrhea 3
• Adequate hydration has been established or is being maintained with oral rehydration solution 1
• The drug is available in your geographic region 1
• Patient is ≥3 months of age 4

Do NOT use racecadotril when:

• Patient has inflammatory diarrhea (bloody stools, high fever) - though it lacks the motility effects that make loperamide dangerous in this setting, evidence for safety is limited 1
• Adequate oral rehydration has not been initiated - fluid replacement remains the cornerstone of treatment 1
• In North America, where the drug is unavailable 1

Comparison with Loperamide

• Racecadotril has a superior safety profile compared to loperamide, with fewer adverse events and less rebound constipation 3
• Unlike loperamide, racecadotril does not slow intestinal transit, theoretically making it safer in bacterial diarrhea 3
• Loperamide is contraindicated in children <18 years with acute diarrhea, whereas racecadotril has been studied in children as young as 3 months 1, 4

Important Caveats

• The primary treatment for acute diarrhea remains oral rehydration therapy - racecadotril is only an adjunct 1, 2
• Despite mechanistic advantages and some positive individual studies, the most recent high-quality systematic review (2019 Cochrane) found insufficient evidence to recommend routine use 2
• Most studies showing benefit were conducted in inpatient settings or resource-limited countries where baseline dehydration and rotavirus prevalence differ from developed nations 2, 6
• The drug appears safe with adverse event rates similar to placebo 2

Practical Recommendation

Given the conflicting evidence between individual trials showing benefit and the Cochrane review showing minimal clinical impact, racecadotril should be reserved for cases where standard oral rehydration is insufficient to control symptoms and the drug is locally available, rather than used routinely 2. The 2017 IDSA guidelines acknowledge its stool-reducing effects but notably do not include it in formal recommendations, partly due to North American unavailability 1.