In which type of diarrhea can you give racecadotril (acetorphan) and when, and when should it be avoided in a patient with diarrhea?

Racecadotril Use in Diarrhea

Racecadotril is recommended for Grade 1 immunotherapy-induced diarrhea in cancer patients as part of symptomatic treatment alongside oral rehydration, and should be avoided in severe (Grade 3-4) diarrhea where loperamide and opioids are contraindicated. 1

When to Give Racecadotril

Immunotherapy-Induced Diarrhea (Primary Indication)

• Grade 1 diarrhea: Use racecadotril or loperamide as antidiarrheal treatment with oral rehydration 1
• This represents mild diarrhea (increase of <4 stools per day over baseline) in cancer patients receiving checkpoint inhibitors (anti-CTLA-4 or anti-PD-1 therapy) 1

Acute Watery Diarrhea (Research Context)

• Racecadotril has demonstrated efficacy in acute watery diarrhea as adjunct to oral rehydration therapy in both adults and children 2, 3, 4, 5
• It reduces stool output by approximately 46-50% and decreases duration of diarrhea 3, 4, 5
• However, a 2019 Cochrane review concluded that while safe, racecadotril has little benefit and is not recommended for routine use in children under 5 years outside clinical trials 6

When to Avoid Racecadotril

Severe Immunotherapy-Induced Diarrhea

• Grade 3 and 4 diarrhea/colitis: Racecadotril, loperamide, and all opioid antimotility agents should be avoided 1
• At this severity level, treatment requires high-dose corticosteroids (1-2 mg/kg/day prednisone equivalent) with IV administration initially 1
• Risk of toxic megacolon and bowel perforation makes antimotility agents dangerous 1

Inflammatory or Bloody Diarrhea

• Antimotility drugs should be avoided in suspected or proven inflammatory diarrhea or diarrhea with fever, as toxic megacolon may result 1
• Grade 2 immunotherapy-induced diarrhea with bloody stools contraindicates simple antidiarrheal therapy 1

Pediatric Use Considerations

• While racecadotril has been studied in children and appears safe, current evidence does not support routine use outside research settings 6
• General antimotility drugs (like loperamide) should not be given to children <18 years with acute diarrhea 1, 7

Clinical Algorithm for Decision-Making

Step 1: Identify the type and severity of diarrhea

• Is this immunotherapy-related? Grade the severity (1-4) 1
• Is there blood in stools, fever, or signs of colitis? 1
• Is the patient adequately hydrated? 1

Step 2: For Grade 1 immunotherapy-induced diarrhea

• Start oral rehydration solution 1
• Add racecadotril OR loperamide as antidiarrheal 1
• Continue immunotherapy 1

Step 3: For Grade 2 immunotherapy-induced diarrhea

• Stop immunotherapy 1
• If NO bloody diarrhea: Consider budesonide 9 mg daily plus symptomatic treatment 1
• If bloody diarrhea, diffuse ulceration, or symptoms persist >3 days: Start oral corticosteroids (0.5-1 mg/kg/day prednisone) 1

Step 4: For Grade 3-4 immunotherapy-induced diarrhea

• AVOID racecadotril, loperamide, and all opioids 1
• Start IV corticosteroids 1-2 mg/kg/day prednisone equivalent 1
• If no improvement in 3-5 days, add infliximab 5 mg/kg 1

Important Caveats

Mechanism of action: Racecadotril is an enkephalinase inhibitor with antisecretory properties that reduces intestinal hypersecretion without affecting motility, distinguishing it from antimotility agents 2, 3, 4

Limited general use: Despite demonstrated efficacy in reducing stool output and duration in research settings, racecadotril is not recommended for routine management of acute gastroenteritis outside the specific context of immunotherapy-induced diarrhea 7, 6

Rehydration priority: Regardless of whether racecadotril is used, adequate rehydration with oral rehydration solution (or IV fluids if severe dehydration) remains the cornerstone of diarrhea management 1, 7

Monitoring requirement: Patients on racecadotril for immunotherapy-induced diarrhea require close monitoring for progression to higher grades, which would necessitate immediate discontinuation and escalation to corticosteroid therapy 1