Impact of guideline awareness in public pharmacies on counseling of patients with acute or chronic constipation in a survey of pharmacy personnel.

BACKGROUND: Constipation is often self-managed by patients and guidelines are available to aid healthcare professionals in the counseling of patients for self-management. Therefore, we have explored the knowledge and attitude of pharmacy personnel towards guidelines for the management of acute and functional chronic constipation and how they affects their recommendations. METHODS: An online survey was conducted among 201 pharmacists and pharmacy technicians from an existing panel. They were presented with two typical cases, a 62-year old woman with functional chronic constipation and a 42-year old woman with travel plans. For each case, they were asked about their treatment recommendations and the underlying rationale. Thereafter, they were provided with contents from an applicable national guideline and asked again about their recommendations and the underlying rationale. In line with the exploratory nature, data were analyzed in a descriptive manner only. RESULTS: Before exposure to guideline content, the most frequent recommendations for chronic constipation were macrogol, fiber and lactulose and for acute constipation sodium picosulfate, bisacodyl and enemas. Following guideline exposure, the most frequent recommendations for chronic constipation were macrogol, bisacodyl and sodium picosulfate and for acute constipation bisacodyl, sodium picosulfate and macrogol (all three equally recommended by the guideline for the management of acute and chronic constipation). Correspondingly, the rationale behind the recommendations shifted with guideline conformity becoming a leading reason. CONCLUSIONS: Awareness of the content of an applicable guideline on the management of constipation was poor among pharmacy personnel. Accordingly, recommendations in many cases were not in line with the guideline. Greater awareness of guideline content is desirable to enable more evidence-based recommendations in the management of constipation.

Racecadotril in the treatment of acute diarrhea in children: a systematic, comprehensive review and meta-analysis of randomized controlled trials.

BACKGROUND: Racecadotril is a guideline-recommended option for the treatment of acute diarrhea in children but existing guidelines and previous reviews of the field are based on a small fraction of published evidence. Therefore, we have performed a systematic search for randomized controlled trials evaluating racecadotril as add-on or in comparison to other treatments. METHODS: A search was performed in PubMed, Scopus and Google Scholar without limits about country of origin or reporting language. A meta-analysis was conducted for the five most frequently used efficacy parameters. RESULTS: We have retrieved 58 trials, from nine countries including six in comparison to placebo, 15 in comparison to various active treatments and 41 as add-on to various standard treatments (some multi-armed studies allowing more than one comparison). Trials used 45 distinct efficacy parameters, most often time to cure, % of cured children after 3 days of treatment, global efficacy and number of stools on second day of treatment. Racecadotril was superior to comparator treatments in outpatients and hospitalized patients with a high degree of consistency as confirmed by meta-analysis for the five most frequently used outcome parameters. For instance, it reduced time to cure from 106.2 h to 78.2 h (mean reduction 28.0 h; P < 0.0001 in 24 studies reporting on this parameter). Tolerability of racecadotril was comparable to that of placebo (10.4% vs. 10.6% adverse events incidence) or that of active comparator treatments other than loperamide (2.4% in both groups). CONCLUSIONS: Based on a comprehensive review of the existing evidence, we conclude that racecadotril is more efficacious than other treatments except for loperamide and has a tolerability similar to placebo and better than loperamide. These findings support the use of racecadotril in the treatment of acute diarrhea in children.

A Comprehensive Comparison of the Efficacy and Tolerability of Racecadotril with Other Treatments of Acute Diarrhea in Adults.

Racecadotril is a guideline-recommended treatment to alleviate symptoms of acute diarrhea. A systematic review of randomized studies was performed comparing efficacy and safety of treatment with racecadotril to that with placebo or active treatments in adults. In five double-blind studies, racecadotril and placebo had comparable tolerability, but racecadotril was more effective. This was consistent across multiple efficacy parameters including duration of diarrhea, number of diarrheic stools, abdominal pain, and meteorism; it was also consistent across countries in Africa, Asia, and Europe. In six randomized studies in outpatients comparing racecadotril to loperamide, resolution of symptoms occurred with similar speed and efficacy; however, racecadotril treatment was associated with less rebound constipation and less abdominal discomfort. The seventh comparative study performed in geriatric nursing home residents reported a superior efficacy of racecadotril. In direct comparison with Saccharomyces boulardii treatment, racecadotril exhibited similar tolerability but was more efficacious. One study compared racecadotril to octreotide in patients with acute diarrhea requiring hospitalization, rehydration, and antibiotic treatment; in this cohort, octreotide was more efficacious than racecadotril. In conclusion, in adults with acute diarrhea, racecadotril is more efficacious than placebo or S. boulardii, similarly efficacious as loperamide and, in patients with moderate to severe disease as add-on to antibiotics, less than octreotide. The tolerability of racecadotril is similar to that of placebo or S. boulardii and better than that of loperamide, particularly with regard to risk of rebound constipation. Taken together, these data demonstrate that racecadotril is a suitable treatment to alleviate symptoms of acute diarrhea in adults.

A comprehensive review of the pharmacodynamics, pharmacokinetics, and clinical effects of the neutral endopeptidase inhibitor racecadotril.

Racecadotril, via its active metabolite thiorphan, is an inhibitor of the enzyme neutral endopeptidase (NEP, EC 3.4.24.11), thereby increasing exposure to NEP substrates including enkephalins and atrial natriuretic peptide (ANP). Upon oral administration racecadotril is rapidly and effectively converted into the active metabolite thiorphan, which does not cross the blood-brain-barrier. Racecadotril has mainly been tested in animal models and patients of three therapeutic areas. As an analgesic the effects of racecadotril across animal models were inconsistent. In cardiovascular diseases such as hypertension or congestive heart failure results from animal studies were promising, probably related to increased exposure to ANP, but clinical results have not shown substantial therapeutic benefit over existing treatment options in cardiovascular disease. In contrast, racecadotril was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal) secretion from the gut without changing gastro-intestinal transit time or motility. This included studies in both adults and children. In direct comparative studies with loperamide in adults and children, racecadotril was at least as effective but exhibited fewer adverse events in most studies, particularly less rebound constipation. Several guidelines recommend the use of racecadotril as addition to oral rehydration treatment in children with acute diarrhea.