Glaxo Wellcome’s new drug for treating irritable bowel syndrome has been
found to produce serious adverse reactions in a small number of patients. The
drug, alosetron (Lotronex), is not yet marketed in the United Kingdom but has
been available in the United States since February.
The US Food and Drug Administration recently issued a warning about gastrointestinal
reactions to the drug. It said that, between February 1 and June 1, it had had
seven reports of serious complications of constipation, resulting in hospitalisation
of six patients, three of whom required surgery. The FDA said that 25 to 30
per cent of patients in clinical trials experienced constipation but it had
received no reports of serious complications before marketing.
There have also been eight reports of ischaemic colitis in patients taking alosetron
since marketing, plus four cases in premarketing studies. All 12 patients recovered
when the drug was discontinued.
Alosetron is a 5HT3 antagonist marketed for treatment of the diarrhoea-predominant
form of irritable bowel syndrome in women. (It has not been shown to help men.)
The FDA comments that irritable bowel syndrome can be severely incapacitating
and that it believes the benefits of alosetron outweigh the risks if the drug
is used acccording to revised instructions. It has asked Glaxo Wellcome to produce
a “medication guide”, which will be supplied with each pack of the
drug. Lotronex is the first drug to have a medication guide, under regulations
that became effective in 1999. The guide contains patient information that US
pharmacists must distribute with products that the FDA has determined “pose
a serious risk, for which patient labelling can help prevent that risk.”
Patients will be advised to contact their doctor straight away if they become
constipated while taking alosetron, and to stop taking the drug immediately
if they develop certain gastrointestinal symptoms, such as abdominal pain or
blood in the stools, which could be early signs of serious side effects.
Glaxo Wellcome has written to pharmacists in the US with details of the reported
reactions to the drug. It said that the serious complications of constipation
included obstruction, perforation, impaction, toxic megacolon and secondary
ischaemia. Prescribing information for the drug has been revised to take account
of new precautions.
In the UK, Glaxo Wellcome is hoping to market alosetron in 2001. A spokesman
for Glaxo Wellcome in the UK said this week that the medication guide should
help to ensure that alosetron was used in the correct patient population.