Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea

Cilansetron is a novel serotonin type-3 (5-hydroxytryptamine; 5-HT) receptor subtype 3 (5-HT(3)) receptor antagonist currently being evaluated for the treatment of female and male patients with irritable bowel syndrome with diarrhoea predominance (IBS-D). 5-HT(3) receptor antagonists such as cilansetron have been shown to affect gastrointestinal motility. Whether cilansetron affects visceral sensation independent of effects on visceral compliance remains controversial. Results from two large, randomised, double-blind, placebo-controlled, parallel-group Phase III clinical trials of cilansetron in patients with IBS-D have recently been presented in abstract form. These studies found that cilansetron was more effective than placebo at improving overall, as well as individual symptoms, including abdominal pain and diarrhoea in female and male IBS-D patients. The most commonly reported side effect with cilansetron has been constipation and, in general, the drug has been well tolerated in clinical trials. Although rare, the most concerning side effect observed with cilansetron has been suspected ischaemic colitis. The event rate for suspected ischaemic colitis associated with cilansetron from clinical trials is 3.77 per 1000 person years of exposure. This rate appears to be greater than that expected in the IBS population and similar to that observed with alosetron, another 5--HT(3) receptor antagonist. All of the cases of suspected ischaemic colitis reported with cilansetron have resolved without serious sequelae. How issues surrounding the safety of cilansetron will affect the approval process in various countries remains to be determined. However, the risk-benefit of cilansetron is likely to be most favourable in patients with IBS-D who have failed to respond to conventional medical therapies. A detailed risk management plan and post-marketing surveillance programme will be required should this drug become available for the treatment of patients with IBS-D.