Prucalopride. In chronic constipation: poorly documented risks

Constipation is a frequent complaint, especially in women and the elderly. It is sometimes drug-induced, and is only occasionally secondary to a functional or organic disorder. The risks associated with constipation are often overestimated. Prucalopride, a 5-HT4 serotonin receptor agonist, chemically related to some neuroleptics, has been authorised in the European Union for symptomatic treatment of chronic constipation in women dissatisfied with laxatives. A combined analysis of 3 randomised double-blind trials in a total of 1999 patients (87.9% women) complaining of chronic constipation showed that about 36% of women considered it effective at a dose of 2 or 4 mg/day, versus 18% of women receiving placebo. Normal bowel movements resumed in respectively 23.6% and 24.7% of patients taking 2 and 4 mg/day prucalopride, versus 11.3% of patients on placebo (p < 0.001). No statistically significant difference was found between the 2 doses of prucalopride. Palpitations were more frequent in patients treated with prucalopride. The incidence of ischaemic cardiovascular events was 0.2% with prucalopride versus 0.1% with placebo. Increases in heart rate and blood pressure were observed in pigs and dogs treated with prucalopride. Prucalopride seems to increase prolactin levels. Tumours of the liver and thyroid were observed in rats. Prucalopride also carries a risk of poorly defined pharmacokinetic and pharmacodynamic interactions. Prucalopride may reduce the efficacy of oral contraceptives. Miscarriages were reported in clinical trials. Prucalopride should not be taken during pregnancy. In addition, all women of child-bearing age should use effective contraception while taking prucalopride. In practice, prucalopride should be avoided. It is better to focus on lifestyle and behavioural changes, and rational use of laxatives.