Cilansetron

Abstract

Irritable bowel syndrome is an extremely common disorder affecting approximately 10-20% of the population of North America and Europe. This disorder is characterized by abdominal pain and altered bowel habit. The altered bowel habit can take a number of forms. These include a predominant diarrhea form, a form with constipation and one in which patients alternate between diarrhea and constipated forms of the disorder. Irritable bowel syndrome to date has not been associated with any excess mortality. However, the morbidity associated with irritable bowel syndrome is quite high. This mainly takes on the form of impairment in health-related quality of life, interference with activities of daily living and a considerable degree of human suffering. Likewise, the economic impact of irritable bowel syndrome is not trivial and has been estimated to be between US$20 to 30 billion in the United States alone. In an effort to address this common disabling disorder, a number of new drugs have been developed. One of the latest is cilansetron, which is a competitive type 3 serotonin (5-HT3) receptor antagonist. In phase III trials, cilansetron has been shown to be efficacious for the relief of a wide spectrum of symptoms related to irritable bowel syndrome with diarrhea both in male and female patients. By and large, cilansetron is extremely well tolerated and highly efficacious. The most common side effect of cilansetron is constipation, which is seen in 3-12% of subjects at 6 months. Ischemic colitis, a side effect associated with previous drugs of this class, has been seen in eight subjects (six women and two men) to date. All of these ischemic colitis events have been self-limited and did not require surgery. Because of its high degree of efficacy, the fact that it is well tolerated by the overwhelming majority of patients and that it shows efficacy in both genders, cilansetron represents a major advance in the treatment of irritable bowel syndrome with diarrhea predominance.