Reassessing the benefits and risks of alosetron: what is its place in the treatment of irritable bowel syndrome?

Functional gastrointestinal disorders such as the irritable bowel syndrome (IBS) cause substantial morbidity and a high amount of healthcare utilisation. However, no direct mortality can be attributed to functional disorders. Hence, drug treatment of IBS must not only be highly efficient to relieve clinical symptoms but also very safe for the long-term use in humans with such chronic disorders. Alosetron is a potent and highly selective serotonin 5-HT(3 )receptor antagonist that in large randomised controlled clinical trials has been shown to be clinically efficient in female patients with diarrhoea-predominant IBS. The efficacy data along with a low number of serious adverse effects in the preclinical and clinical trials suggested a favourable benefit/risk profile that led to US FDA approval of alosetron in early 2000. However, postmarketing experience has proven that several serious adverse effects, including death, occurred in the treated patient population, which resulted (for a time) in the withdrawal of alosetron from the US market by the producer (GlaxoSmithKline). In the meantime, both public pressure and the proposal of a careful postmarketing surveillance have led the FDA to re-approve alosetron to the US drug market under severe restrictions. These restrictions aim to ensure a safer use of the drug with a more favourable safety profile. Under these restrictions, however, it is not very likely that alosetron will become a major treatment option for many patients, but presumably the continued use of this first selective serotonin antagonist will open an avenue for the development of similar drugs with more favourable benefit/risk profiles in the near future.