Zelnorm

(tegaserod maleate, Novartis)

A serotonin-4 receptor (5-[HT.sub.4]) agonist for short-term treatment of women with constipation-predominant irritable bowel syndrome (IBS), the second IBS drug and the first approved for this specific type of IBS.

* Recommended Dosage: 6 mg twice a day, before meals, for 4-6 weeks. Another 4-6 weeks can be considered for responders.

* Special Considerations: In studies, diarrhea was reported by 9% of patients on Zelnorm vs. 4% of those on placebo; most cases were one episode, occurred during the first week of therapy, and resolved as treatment continued; 1.6% of those on Zelnorm stopped treatment because of diarrhea. More patients on Zelnorm had abdominal surgery: 9 patients (0.3%) on Zelnorm vs. 3 (0.2%) on placebo, due mainly to more cholecystectomies among the former. No causal relationship has been established, the Food and Drug Administration said, Not for patients with diarrhea-predominant lBS.

* Comment: Zelnorm activates g[HT.sub.4] receptors in the GI tract, thereby stimulating the peristaltic reflex and intestinal secretion, and inhibiting visceral sensitivity This drug is the first that can alleviate the three cardinal symptoms of the typical patient with constipation-predominant IBS: abdominal pain, constipation, and bloating, said Dr. John Johanson, a principal investigator in the trials and a gastroenterologist in private practice in Rockford, Ill. He is on the speakers' bureau for and has served as a consultant to Novartis.

In three studies of 2,430 women with IBS symptoms that included abdominal pain, bloating, and constipation, significantly more of those on Zelnorm had a response (considerably or completely relieved of symptoms for at least 2 of 4 weeks) during the first and third months of treatment.

During the first month, response rates were 13%-14% greater among those treated with Zelnorm. During the third month, the difference was 5% greater in two studies and 11% greater in one study, indicating that the drug's effectiveness "may decrease over time," the FDA said in a statement. Response rates ranged from 31% to 44% in Zelnorm-treated patients.

The approval of Zelnorm came more than 2 years after an FDA advisory panel recommended approval; conflicting efficacy data and unresolved safety questions led the FDA to request more data from the manufacturer.

One issue discussed at that meeting was the higher number of ovarian cysts in subjects treated with Zelnorm (eight cases vs. one in placebo patients). An advocacy group, Public Citizen's Health Research Group, wrote a letter to the FDA a year ago, calling for an ultrasound study that could assess the drug's role in ovarian cyst formation, but such a study has not been done. Ovarian cysts are listed in the product labeling among the adverse events that were reported more frequently in patients on Zelnorm than on placebo, and that are "possibly related" to the drug.

COPYRIGHT 2002 International Medical News Group
COPYRIGHT 2002 Gale Group