Linaclotide. A bacterial enterotoxin derivative with a laxative action, nothing more

When patients complain of recurrent functional bowel disorders consisting of alterations in intestinal transit with abdominal pain or discomfort, treatment is purely symptomatic. Increased intake of dietary fibre or use of a bulk-forming or osmotic laxative is used when constipation is the main complaint. Linaclotide, a small peptide closely related to certain toxins secreted by diarrhoea-causing strains of Escherichia coli, has been authorised in the European Union for the treatment of adults with recurrent functional bowel disorders consisting mainly of constipation. Clinical evaluation of linaclotide includes no trials versus other laxatives. It is based on two placebo-controlled trials including a total of about 1600 patients, lasting 3 and 6 months. A pooled analysis of the results obtained at 3 months showed more frequent "relief" with linaclotide than with placebo. Adverse effects included gastrointestinal disorders, with diarrhoea occurring in one in five patients. Diarrhoea was sometimes severe or prolonged. About 10% of patients discontinued linaclotide because of gastrointestinal adverse effects (diarrhoea in half of these cases). The consequences of diarrhoea can be severe, particularly in patients predisposed to fluid and electrolyte imbalances. Co-administration of other laxative substances enhances the laxative effect of linaclotide. The laxative action is likely to reduce the gastrointestinal absorption of co-administered medications. Linaclotide should be avoided during pregnancy, as there are no relevant safety data. In practice, given the absence of head-to-head comparisons with other laxatives, linaclotide is currently just another laxative with no proven advantages over existing first-line options.