he US Food and Drug Administration (FDA) has approved the reintroduction of tegaserod oral tablets (Zelnorm; Sloan Pharma) for irritable bowel syndrome with constipation (IBS-C) in women younger than age 65; therefore US WorldMeds Holdings has announced. “They are excited about what the reintroduction of Zelnorm means for patients suffering from irritable bowel syndrome with constipation.
They have continually heard from patients and clinicians alike that the IBS-C community is eager to have Zelnorm return to the US as an available treatment option;” P. Breckinridge Jones, CEO of US WorldMeds, said in the news release. “The re-approval of Zelnorm is very good news for patients. We believe it will provide renewed access to a treatment option where other new medications have been insufficient for meeting patients’ needs;” added Jeffery Roberts, patient advocate and founder of the IBS Patient Group.
Tegaserod for IBS-C has had a checkered past. The drug was first approved by the FDA in 2002 for the short-term treatment of women with IBS-C. It is suspend from the US market in March 2007 due to potential cardiovascular (CV) safety concerns. In July 2007; the FDA announced that it would allow restrict use of the drug for IBS-C and chronic idiopathic constipation in women younger than 55 years with no history of heart problems.
Last October, following a safety review; the FDA’s Gastrointestinal Drugs Advisory Committee (GIDAC) recommended overwhelmingly (11 yes, 1 no) to recommend reintroducing tegaserod for IBS-C in women without a history of CV ischemic disease and who have no more than one risk factor for CV disease.
The committee reviewed clinical data from 29 placebo-controlled trials and newly-available sources of treatment outcome data. Pooled data from the clinical trials showed a statistically nonsignificant trend toward increased angina among those who took the drug in the clinical trial on which the drug’s approval was based in 2002; however; a recent analysis of 18,000 participants in the entire clinical database found adverse CV events in 13 of 11,614 patients (0.11%) taking tegaserod; compared with only one patient (0.01%) out of 7031 in the placebo group; a difference that was statistically significant; according to information in an FDA briefing document for the committee.
Imbalance in CV
“While an imbalance in CV safety events associated with tegaserod was noted, the strength of the signal was difficult to interpret due to limitations of the meta-analysis for example; the trials were not designed to specifically evaluate CV safety, were of short duration; included a low CV-risk population, and involved retrospective assessment of CV information.
In addition, the etiology of [CV ischemic] events related to the use of tegaserod is not well understood;” the FDA explained in the briefing document. Tegaserod is the only selective serotonin-4 (5-HT4) receptor agonist approved to treat IBS-C, US WorldMeds notes in the release.