Linaclotide for treatment of irritable bowel syndrome--the view of European regulators.

Irritable bowel syndrome (IBS) is a chronic functional gastroinestinal disorder characterised by intestinal pain or discomfort ogether with alteration of bowel habit, abdominal distension, loating, constipation or diarrhoea [1–4]. Symptoms usually wax nd wane for many years, often resulting in reduced quality of life nd work productivity. The pathophysiology of IBS is incompletely nderstood. Despite affecting 5–20% of the Western population, no medicine as authorised in the European Union specifically for the treatent of IBS until recently. Patients and prescribers were limited o general symptomatic treatments such as laxatives, antidiarhoeals and antispasmodics, which are recommended in current uidelines but on the basis of weak evidence [1,5,6]. Alternatively, hey may use unapproved treatments such as antidepressants and on-absorbable antibiotics when lifestyle modifications such as educing stress, altering diet or psychological interventions have hown to be ineffective. On 26 November 2012, the European-wide marketing authoriation of Constella (linaclotide) was issued for adults with moderate o severe IBS with constipation (IBS-C), a common subtype of the isease. This authorisation is based on a positive recommendaion from the European Medicines Agency’s (EMA’s) Committee for edicinal Products for Human Use (CHMP) [7]. The recommended ose is one capsule (290 g) once daily, to be taken at least 30 min efore a meal. Linaclotide, a synthetic 14-amino-acid peptide, is new oral compound that works by increasing intestinal fluid ecretion and accelerated transit. It stimulates guanylate-cyclaseubtype-C (GC-C) receptors on the luminal surface of the intestinal pithelium, leading to increased intraand extracellular levels of yclic guanosine monophosphate (cGMP). The increase in intraellular cGMP in turn activates the cystic fibrosis transmembrane onductance regulator (CFTR), leading to secretion of chloride and icarbonate into the intestinal lumen [7–10].