What is the treatment protocol for a patient with acute or chronic diarrhea using Racecadotril (acetorphan), considering their medical history and demographics?

Racecadotril Treatment Protocol for Acute and Chronic Diarrhea

Racecadotril is recommended as first-line symptomatic treatment for Grade 1 immunotherapy-induced diarrhea in cancer patients and can be used interchangeably with loperamide, offering the advantage of antisecretory action without slowing intestinal transit or increasing toxic megacolon risk. 1, 2

Mechanism and Clinical Advantage

Racecadotril works through enkephalinase inhibition, providing antisecretory effects rather than antimotility effects like loperamide. 2 This mechanism offers a critical safety advantage: it does not slow intestinal transit or increase the risk of toxic megacolon in inflammatory conditions. 2 The drug inhibits pathologic secretion from the gut without changing gastrointestinal transit time or motility. 3

Dosing Protocol

Adults

• Standard dose: 100 mg orally three times daily 4, 5
• Combine with oral rehydration therapy for optimal outcomes 1

Children (3 months to 5 years)

• Dose: 1.5 mg/kg orally every 8 hours 6
• Always administer as adjunct to oral rehydration solution 7, 6

Clinical Context and Grading

Immunotherapy-Induced Diarrhea (Cancer Patients)

Grade 1 diarrhea:

• Use racecadotril OR loperamide with oral rehydration as symptomatic treatment 1
• This carries Level III evidence with Grade A recommendation from ESMO 2

Grade 2 diarrhea:

• Add budesonide 9 mg once daily if no bloody diarrhea 1
• Escalate to oral corticosteroids (0.5-1 mg/kg/day prednisone equivalent) if diffuse ulceration, bleeding, or persistent symptoms after 3 days 1

Grade 3-4 diarrhea:

• Avoid loperamide and opioids at this stage 1
• Use intravenous corticosteroids (1-2 mg/kg/day prednisone equivalent) 1

Efficacy Evidence

Adult Acute Diarrhea

• Racecadotril produces significant reduction in stool weight during the first day of treatment compared to placebo (P = 0.025) 5
• Significantly fewer diarrheal stools after 1 day of treatment versus placebo (P = 0.027) 5
• Similar efficacy to loperamide but with less rebound constipation and less abdominal discomfort 4
• More efficacious than placebo or Saccharomyces boulardii 4

Pediatric Acute Diarrhea

• In hospitalized boys with acute watery diarrhea, racecadotril reduced 48-hour stool output by 46% (92 g/kg vs 170 g/kg with placebo, P<0.001) 6
• Median duration of diarrhea was 28 hours with racecadotril versus 72 hours with placebo (P<0.001) 6
• However, a 2019 Cochrane review concluded that racecadotril has little benefit in improving acute diarrhea in children under five and does not support routine use outside placebo-controlled trials 7

Safety Profile

• Tolerability similar to placebo 4, 5
• Fewer adverse events than loperamide, particularly less rebound constipation 4, 3
• In pediatric studies, only mild and transient adverse effects reported 6
• Overall adverse event rate not increased (RR 0.90,95% CI 0.66 to 1.22) 7
• Does not cross the blood-brain barrier 3

Critical Caveats

When NOT to use racecadotril:

• Grade 3-4 immunotherapy-induced diarrhea/colitis (use corticosteroids instead) 1
• Severe disease requiring hospitalization and antibiotics (octreotide is more efficacious in this setting) 4

Pediatric consideration:

• Despite positive individual trial results, current systematic review evidence does not support routine use in children under five outside research settings 7

Dietary Modifications (Adjunctive)

• Avoid spices, coffee, and alcohol 1
• Reduce insoluble fiber intake 1
• Avoid milk and dairy products (except yogurt and firm cheeses) during chemotherapy-related diarrhea 1