Tegaserod (Zelmac®, Norvatis) was registered in Singapore in April 2002. It is a serotonin 5-HT4 receptor partial agonist indicated for the symptomatic treatment of abdominal pain and discomfort, bloating and altered bowel function relating to irritable bowel syndrome (IBS) in female patients whose main symptoms are pain/discomfort and constipation.
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FDA updates tegaserod label with new risk information
The US Food and Drug Administration (FDA) has recently approved the amended package insert of Zelmac® to include safety information regarding diarrhoea with serious complications associated with the drug and post-marketing reports of ischaemic colitis (IC). In conjunction with FDA's announcement, the manufacturer, Norvatis, issued a letter to health professionals in the US highlighting the label changes which include the following:
a) Serious consequences of diarrhoea (such as hypovolaemia, hypotension and syncope, some of which required hospitalisation for rehydration) have been reported in the clinical studies (0.04%) and during the post-market use of the drug. The drug should be discontinued immediately in patients who develop hypotension or syncope, and should not be initiated in patients who are currently experiencing or frequently experience diarrhoea.
b) Ischaemic colitis has been reported in patients receiving tegaserod during the marketed use of the drug. The drug should be discontinued in patients who develop symptoms of IC (such as rectal bleeding, bloody diarrhoea or new or worsening abdominal pain). The patients should be evaluated promptly and have appropriate diagnostic testing performed. Treatment with tegaserod should not be resumed in patients who develop findings consistent with IC.
a) Serious consequences of diarrhoea (such as hypovolaemia, hypotension and syncope, some of which required hospitalisation for rehydration) have been reported in the clinical studies (0.04%) and during the post-market use of the drug. The drug should be discontinued immediately in patients who develop hypotension or syncope, and should not be initiated in patients who are currently experiencing or frequently experience diarrhoea.
b) Ischaemic colitis has been reported in patients receiving tegaserod during the marketed use of the drug. The drug should be discontinued in patients who develop symptoms of IC (such as rectal bleeding, bloody diarrhoea or new or worsening abdominal pain). The patients should be evaluated promptly and have appropriate diagnostic testing performed. Treatment with tegaserod should not be resumed in patients who develop findings consistent with IC.
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Comments
The FDA's regulatory action follows the worldwide post-marketing reports of 21 cases of diarrhoea with serious consequences, 21 cases of IC and 3 cases of other forms of intestinal ischaemia. To-date, HSA has not received any local reports of serious ADRs associated with tegaserod.
As the current information is based on spontaneous ADR reports, a causal relationship between tegaserod and IC has not been established. Placebo controlled clinical trials of 7,000 patients for 3-month duration showed no cases of these events, and would suggest that the rate of these events is low. Observational population-based studies have suggested that IBS is one of the risk factors that increases the incidence of IC.
HSA is working with the company to update the local package insert to reflect the new safety information.
As the current information is based on spontaneous ADR reports, a causal relationship between tegaserod and IC has not been established. Placebo controlled clinical trials of 7,000 patients for 3-month duration showed no cases of these events, and would suggest that the rate of these events is low. Observational population-based studies have suggested that IBS is one of the risk factors that increases the incidence of IC.
HSA is working with the company to update the local package insert to reflect the new safety information.
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References
- Higgins PD et. al. Systematic review: the epidemiology of ischaemic colitis. Aliment Pharmacol Ther. 2004 Apr 1;19(7):729-38.2.
- Cole JA et. al. The occurrence of colonic ischemia, complications of constipation, and bowel surgery in relation to irritable bowel syndrome. Pharmacoepidemiology and Drug Safety 11:S0-S0(2002); S28.
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