prucalopride and Diarrhea

There has been no definitive systematic review and meta-analysis to date examining the effect of laxatives and pharmacological therapies in chronic idiopathic constipation (CIC).. To assess efficacy of these therapies systematically in CIC.. Systematic review and meta-analysis of randomised controlled trials (RCTs).. MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (up to September 2010).. Placebo-controlled trials of laxatives or pharmacological therapies in adult CIC patients were eligible. Minimum duration of therapy was 1 week. Trials had to report either a dichotomous assessment of overall response to therapy at last point of follow-up in the trial, or mean number of stools per week during therapy.. Symptom data were pooled using a random effects model. Effect of laxatives or pharmacological therapies compared to placebo was reported as RR of failure to respond to therapy, or a weighted mean difference (WMD) in mean number of stools per week, with 95% CIs.. Twenty-one eligible RCTs were identified. Laxatives (seven RCTs, 1411 patients, RR=0.52; 95% CI 0.46 to 0.60), prucalopride (seven trials, 2639 patients, RR=0.82; 95% CI 0.76 to 0.88), lubiprostone (three RCTs, 610 patients, RR=0.67; 95% CI 0.56 to 0.80), and linaclotide (three trials, 1582 patients, RR=0.84; 95% CI 0.80 to 0.87) were all superior to placebo in terms of a reduction in risk of failure with therapy. Treatment effect remained similar when only RCTs at low risk of bias were included in the analysis. Diarrhoea was significantly more common with all therapies.. Only two RCTs were conducted in primary care, and total adverse events data for laxatives and linaclotide were sparse.. Laxatives, prucalopride, lubiprostone and linaclotide are all more effective than placebo for the treatment of CIC.

Topics: Alprostadil; Benzofurans; Chronic Disease; Constipation; Diarrhea; Humans; Laxatives; Lubiprostone; Peptides; Randomized Controlled Trials as Topic; Treatment Outcome

Prucalopride is effective at alleviating symptoms of chronic constipation in women. The aim of this study was to assess the efficacy of 12 weeks of prucalopride treatment compared with placebo in men with chronic constipation.. This was a multicenter, stratified, randomized, parallel-group, double-blind, placebo-controlled, phase 3 study (ClinicalTrials.gov identifier: NCT01147926). The primary end point was the proportion of patients with a mean of three or more spontaneous complete bowel movements (SCBMs) per week across the treatment period. Efficacy end points were assessed using daily electronic diaries, global assessment of the severity of constipation and efficacy of treatment, and Patient Assessment of Constipation-Symptoms (PAC-SYM) and Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaires.. In total, 374 patients were enrolled in the study. Significantly more patients achieved a mean of three or more SCBMs per week in the prucalopride group (37.9%) than in the placebo group (17.7%, P<0.0001). The proportion of patients rating their constipation treatment as "quite a bit" to "extremely" effective at the final on-treatment visit was 46.7 and 30.4% in the prucalopride and placebo groups, respectively. The difference between treatment groups was statistically significant (P<0.0001). The proportion of patients with an improvement of at least 1 point in PAC-QOL satisfaction subscale score was 52.7 and 38.8% in the prucalopride and placebo groups, respectively (P=0.0035). Prucalopride had a good safety profile and was well tolerated.. Prucalopride is effective, has a good safety profile, and is well tolerated for the treatment of men with chronic constipation.

Topics: Abdominal Pain; Adult; Aged; Benzofurans; Chronic Disease; Defecation; Diarrhea; Double-Blind Method; Headache; Humans; Male; Medical Records; Middle Aged; Nausea; Quality of Life; Serotonin 5-HT4 Receptor Agonists; Severity of Illness Index; Surveys and Questionnaires

This integrated analysis aimed to identify the factors associated with the most frequently re-ported treatment-emergent adverse events (TEAEs) in Asian and non-Asian patients with chronic constipation (CC) who receive prucalopride or placebo over 12 weeks.. Pooled data from four randomized, double-blind, placebo-controlled, multicenter, phase III studies (NCT00488137, NCT00483886, NCT00485940, and NCT01116206) on pa-tients treated with prucalopride 2 mg or placebo were ana-lyzed. The associations between predictors and TEAEs were evaluated based on a logistic regression model.. Overall, 1,821 patients (Asian, 26.1%; non-Asian, 73.9%) were analyzed. Prucalopride treatment was significantly as-sociated with diarrhea, headache, and nausea (p<0.001), but not with abdominal pain, compared with placebo. Differ-ences in the prevalence of TEAEs between prucalopride and placebo decreased greatly after the first day of treatment. Compared with non-Asians, Asians were more likely to expe-rience diarrhea and less likely to develop abdominal pain, headache, and nausea. Prior laxative use, CC duration, and body weight were not predictive of any of these TEAEs. Con-clusions Prucalopride treatment was positively associated with diarrhea, headache, and nausea. Asian patients tended to have a higher frequency of diarrhea but lower frequencies of headache, abdominal pain, and nausea compared with non-Asians. (Gut Liver, 2015;9208-213).

Topics: Abdominal Pain; Adult; Aged; Aged, 80 and over; Asian People; Benzofurans; Clinical Trials, Phase III as Topic; Constipation; Diarrhea; Double-Blind Method; Female; Headache; Humans; Male; Middle Aged; Multicenter Studies as Topic; Nausea; Randomized Controlled Trials as Topic; Regression Analysis