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8/15/2000

Alosetron Approved for Treatment of Irritable Bowel Syndrome

Jane L. Miller

Glaxo Wellcome has received approval to market a serotonin-receptor antagonist, alosetron hydrochloride (Lotronex), for use by women with diarrhea-predominant irritable bowel syndrome (IBS). The company expected to introduce the product by mid-March.

In dose-ranging studies of alosetron, only women appeared to benefit from treatment. Thus, only women with diarrhea-predominant IBS were enrolled in efficacy studies of the drug. In these studies, alosetron proved superior to placebo in relieving the pain and discomfort associated with IBS. Alosetron also reduced stool frequency, improved stool consistency, and reduced the proportion of days with urgency. 

In the clinical trials, constipation was reported by 25-30% of patients taking alosetron and prompted 10% of patients to stop taking the drug. Other adverse events occurred at similar frequencies with placebo and alosetron. Four cases of acute ischemic colitis were reported in alosetron-treated patients during the studies. 

Alosetron is rapidly absorbed after oral administration, is 50-60% bioavailable, and has a terminal elimination half-life of about 1.5 hours. At least 13 metabolites have been detected. The metabolic pathways involve cytochrome P-450 (CYP) 2C9, 3A4, and 1A2, as well as non-CYP Phase I conversion reactions. Only about 6% of a dose is eliminated unchanged in the urine. 

Alosetron does not appear to interfere with the clearance of drugs metabolized by the major CYP isoenzymes. 

The recommended dosage of alosetron is 1 mg orally twice daily. Lotronex is supplied as 1-mg tablets in bottles of 60 and 120 and unit dose packages of 60.