A multinational comparison of racecadotril and loperamide in the treatment of acute watery diarrhoea in adults

BACKGROUND: Racecadotril (acetorphan) is an orally active, potent inhibitor of enkephalinase, which exerts an antihypersecretory effect without increasing intestinal transit time. The aim of this study was to compare the efficacy, safety and tolerability of racecadotril with those of loperamide by assessing their effects on the resolution of the signs and symptoms of diarrhoea in patients in developing countries who had acute watery diarrhoea of less than 5 days' duration. METHODS: 945 outpatients from 21 centres in 14 countries received racecadotril (100 mg) or loperamide (2 mg) three times daily in a single-blind study. Duration of diarrhoea was the primary measure of efficacy; secondary criteria were overall clinical response, occurrence and duration of abdominal pain and distension, and occurrence of other associated signs and symptoms. Occurrence of constipation and adverse events were the main safety assessments. RESULTS: Diarrhoea resolved rapidly with both racecadotril and loperamide (55.0 h in both groups), 92% of patients on racecadotril and 93% on loperamide being treatment successes. Racecadotril produced a significantly greater reduction in abdominal pain and distension than loperamide (P = 0.024 and 0.03, respectively). The duration of abdominal distension was significantly shorter with racecadotril (5.4 versus 24.4 h; P = 0.0001), and constipation was also significantly less frequent (16% versus 25%; P = 0.001). One-hundred-and-eighty patients (19%) experienced one or more adverse event during the study: 67 (14.2%) in the racecadotril group and 113 (23.9%) in the loperamide group (P = 0.001). CONCLUSIONS: Racecadotril resolved the symptoms of acute diarrhoea rapidly and effectively, and produced more rapid resolution of abdominal symptoms and less constipation than loperamide.