Hidrasec: novel antihypersecretory agent for acute diarrhoea

Racecadotril is an antidiarrhoeal with a novel mechanism of action licensed for use in adults and as an adjunct to oral rehydration in children aged three months and over.

Racecadotril is the only agent licensed in the UK for the treatment of acute diarrhoea in infants and children from three months
Racecadotril is the only agent licensed in the UK for the treatment of acute diarrhoea in infants and children from three months

PHARMACOLOGY

Racecadotril is an antihypersecretory agent. It inhibits the enzyme enkephalinase in the small intestine, thereby reducing the intestinal hypersecretion of water and electrolytes induced by cholera toxin or inflammation. Racecadotril does not affect basal secretory activity and exerts rapid antidiarrhoeal action without modifying intestinal transit time.1

CLINICAL STUDIES

Meta-analysis in children

The efficacy of racecadotril in the treatment of watery diarrhoea was demonstrated in a meta-analysis of individual patient data from 9 randomised controlled trials involving 1,384 children (aged 1 month to 15 years, median 12 months) with acute diarrhoea of varying severity. All trials compared the effectiveness of racecadotril plus oral rehydration solution with placebo, oral rehydration solution alone or kaolin-pectin.1,2

The primary outcome measure used in the meta-analysis was the duration of diarrhoea, calculated as the period between the first drug intake and the last unformed stool before recovery (defined as the occurrence of 2 consecutive formed stools or no stool for 12 hours). Other endpoints were stool output during the first 48 hours (inpatient trials) and the total number of diarrhoeic stools until recovery (outpatient trials).2

The overall median duration of diarrhoea after study treatment was 1.75 days for racecadotril compared with 2.81 days for placebo. The proportion of recovered patients was significantly greater in the racecadotril groups, with more than twice as many patients recovered at any time compared with the placebo group (hazard ratio 2.04; p<0.001).2

In inpatient studies (n=637), the ratio of mean stool output for racecadotril versus placebo was 0.59 (p<0.001). For outpatient studies (n=695), the ratio of the mean number of diarrhoeic stools for racecadotril versus placebo was 0.63 (p<0.001).2

All findings were irrespective of baseline dehydration level and rotavirus status. There were no significant differences in the rate of adverse events for racecadotril compared with placebo.2 

Efficacy vs loperamide in children

In a separate study of 102 children aged 2 to 10 years, racecadotril was found to be as effective as loperamide in treating acute diarrhoea. However, racecadotril had a superior tolerability and safety profile with significantly more patients in the loperamide group experiencing constipation (58% versus 36.5%; p=0.03).3

Studies in adults

Use of racecadotril in adults with acute diarrhoea was assessed in a double-blind study (n=70) comparing a dose of 100mg three times daily with placebo. Racecadotril was associated with a 28.9% decrease in stool weight during the first day of treatment compared with placebo (p=0.025). In addition, the mean number of diarrhoeic stools passed after one day of treatment was significantly lower in the racecadotril group than in the placebo group (4.3 versus 5.4; p=0.027).4

Racecadotril and placebo had a similar tolerability profile in this study, with 3.1% of patients on racecadotril reporting adverse events on day 4 compared with 5.3% of those on placebo.4 

In another study to compare the efficacy of racecadotril and loperamide in the treatment of acute watery diarrhoea in adults (n=944), the two drugs were associated with a similarly rapid resolution of diarrhoea. However, racecadotril was found to produce significantly faster resolution of abdominal distension (p=0.0001) and significantly less constipation than loperamide (p=0.001).5

Tolerability

The predominant adverse effects in paediatric patients treated with racecadotril were tonsillitis, rash and erythema, although these were all seen uncommonly. The most commonly reported adverse event in adults was headache.1

References:

  1. Hidrasec Summaries of Product Characteristics, June 2012.
  2. Lehert P et al. Dig Liver Dis 2011; 43: 707-13.
  3. Turck D et al. Aliment Pharmacol Ther 1999; 13 (Suppl 6): 27-32.
  4. Hamza H et al. Aliment Pharmacol Ther 1999; 13 (Suppl 6): 15-19.
  5. Prado D. Scand J Gastroenterol 2002; 37: 656-61.

View Hidrasec drug record
 
Further information: Abbott

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