What is the evidence.
See evidence matrix  in Epistemonikos later

We found five systematic reviews [1],[2],[3],[4],[5] including ten randomized controlled trials, reported in nine references [6],[7],[8],[9],[10],[11],[12],[13],[14] (one reference reports two studies [12]). One of the trials [14] compares racecadotril with loperamide, so we did not include it in the analysis.

What types of patients were included

All trials restricted inclusion to pediatric population, between 3 to 71 months old, with acute diarrhea of viral or bacterial etiology. Four studies considered inpatients only [6],[7],[10],[12] and five outpatients only [8],[9],[11],[12],[13]. Stool output and number of diarrheic stools per day before inclusion were registered, showing no difference between racecadotril and placebo groups. 

What types of interventions were included

Trials evaluated oral racecadotril; in six the dose was 1.5 mg/kg [6],[7],[8],[9],[10],[11], two administered 10 mg or 20 mg three times a day adjusted by body weight (over or under 9 kg) [12] and one did not specify dosage [13]

What types of outcomes
were measured

Proportion of responders (defined as diarrhea duration less than 48 hours), proportion of patients not cured at fifth day of therapy, daily stool output and volume, number of vomits the first 48 hours of treatment and adverse effects reported during treatment. 

To whom this evidence does and does not apply

• This evidence applies to pediatric patients with clinical diagnosis of acute diarrhea of viral or bacterial etiology, hospitalized or in ambulatory care.
• This evidence does not apply to immunosuppressed patients or with severe comorbidity. 

• We selected “proportion of responders” as outcome because it was the only outcome critical for decision-making according to the opinion of the authors of this summary. It was also the only one included in all randomized trials available and was subject of individual patient analysis in one of the systematic reviews [5] included in this summary.
• This update includes one meta-analysis reporting adverse effects with racecadotril, providing quantitative data about the safety of this therapy.
• It might be relevant to address outcomes such as need for hospitalization, need for intravenous hydration, additional emergency department visits, among others. 

• Racecadotril is a safe therapy for pediatric population [15]. There was no difference in the rate of adverse effects reported between groups. Events reported for placebo and racecadotril groups included vomiting, abdominal distension, abdominal pain, rash and one case of aminotransferase level increase (racecadotril) [1].
• None of the studies reported important adverse effects with racecadotril. It is also an approved therapy for pediatric population [14].
• The certainty of the evidence is moderate, but there is a probable benefit of the intervention in terms of decreasing diarrhea duration and it would be a low risk therapy. 

• Racecadotril is a complement to acute diarrhea treatment and does not replace the use of oral rehydration solutions.
• Pediatric practice involves parents and/or patient caregivers. It is important to consider their concerns about disease. In this scenario and highlighting acute diarrhea is usually a self-limited condition, it is reasonable to suggest racecadotril as an adjuvant therapy that may have benefits but involves costs.

• Racecadotril is still not widely available and adds costs to standard treatment for acute diarrhea (oral rehydration solution). Considering it would shorten the duration of the disease which might lower risk of dehydration, using racecadotril could decrease costs (hospital bed use, emergency department visits). However, it is not possible to make an appropriate cost-benefit analysis with the evidence available, especially because of the lack of information on other important outcomes. 

Differences between this summary and other sources

• Our summary is consistent with the systematic reviews identified.
• The new evidence incorporated in this update does not change conclusions from the previous version. One of the systematic reviews [1] adds a multiple comparisons (network) meta-analysis; it shows racecadotril was better when compared to placebo or other adjuvants. Nevertheless, the difference in methods does not allow comparison with the other systematic reviews considered in this summary.
• We reviewed the Evidence-Based Guidelines for the Management of Acute Gastroenteritis in Children of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Pediatric Infectious Diseases [16]. Their recommendations are consistent with the conclusion of our summary. 

• The certainty of the available evidence is moderate, although only one outcome about efficacy was analyzed.
• We are aware of ongoing randomized controlled trials about racecadotril for acute diarrhea in children and a new systematic review with a network meta-analysis with the aim to determine the relative effectiveness of pharmacological and nutritional treatments for reducing the duration of acute diarrhea in children [17]. So it is possible that they provide new information for this question in the future.