Alosetron in irritable bowel syndrome: strategies for its use in a common gastrointestinal disorder.
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterised by recurrent abdominal pain and altered bowel habits in the absence of any discernible structural, biochemical and physiological abnormalities. Although there is no specific biological marker for the diagnosis of this disorder, recently developed symptom-based criteria provide the tools necessary to make a diagnosis. The precise underlying pathophysiology of IBS remains unknown. However, disturbances in the brain-gut axis involving the central nervous system and the enteric nervous system have emerged as an underlying concept for IBS. In this regard, conventional treatment has been recognised as unsatisfactory for many patients with IBS and novel, neuroenteric modulatory compounds have been introduced for use by clinicians. Specifically, compounds interacting with the 5-hydroxytryptamine (5-HT, serotonin) receptors of the 5-HT3 and 5-HT4 subtype have been demonstrated of benefit in some patients for the treatment of IBS. In this leading article, we present the current data on the pharmacology, clinical trials, indications and adverse effects of alosetron, a potent and selective 5-HT3 antagonist. As a result of the recognition of serious adverse effects, the indication for alosetron has been restricted and it is now indicated only for women with severe diarrhoea-predominant IBS who have symptoms for at least 6 months and who have failed to respond to conventional therapy. Prescribing restrictions and the risk-management programme implemented as required by the US FDA is reviewed along with a summary of the studies to be performed after reintroduction of alosetron to monitor safety.
Lembo
Anthony
A
Department of Gastroenterology, Beth Israel Deaconess Hospital, Boston, Massachusetts 02215, USA. alembo@bidmc.harvard.edu
Weber
H Christian
HC
Farraye
Francis A
FA
D002243:Carbolines / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000075202:Contraindications; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000175:diagnosis / Q000188:drug therapy*; D011788:Quality of Life; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D012737:Sex Factors; D014481:United States; D014486:United States Food and Drug Administration
D002243:Carbolines; D005765:Gastrointestinal Agents; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; C090840:alosetron; D012701:Serotonin