Zelnorm - Short-term treatment option for women with constipation-predominanat irritable bowel syndrome.
Tegaserod is a selective partial agonist at the serotonin-4 (5-HT4) receptor and possesses gastrointestinal prokinetic activity. Growing evidence suggests 5-HT plays a pivotal role in the maintenance of overall GI motor function. Activation of 5-HT4 receptors in the GI tract by tegaserod stimulates the peristaltic reflex and intestinal secretion, in addition to inhibiting visceral sensitivity. Tegaserod, by acting as an agonist at neuronal 5-HT4 receptors, triggers the release of further neurotransmitters such as calcitonin gene-related peptide from sensory neurons. The drug has minimal to no binding affinity for 5-HT3, dopamine, muscarinic, histamine (H1), opioid, or alpha-1 or alpha-2 adrenergic receptors.
|Volume of distribution||368 L|
|Metabolism||Presystemic hydrolysis in stomach followed by oxidation and conjugation in liver to inactive metabolites|
|Excretion||Feces (67%) Urine (33%)|
|Half-life (terminal)||11 hours|
The approval of tegaserod was based on the results of three 12-week, multicenter, controlled clinical trials involving 2,470 women with constipation-predominant IBS. The primary efficacy end point in these studies was the subject's global assessment (SGA) of relief of IBS symptoms overall. Secondary end points included the individual symptoms of abdominal pain/discomfort and bloating. Study results showed that the proportion of patients responding to tegaserod therapy after one month ranged from 31%-35%, compared with 17%-22% for the placebo group. After three months of therapy, the proportion of responders was 39%-44% for tegaserod patients, compared with 28%-39% for placebo patients. In addition, tegaserod-treated patients experienced less abdominal pain/discomfort and bloating and had an increase in the number of bowel movements per week compared with placebo patients during the study period. Comparative studies with other agents used for the treatment of IBS are not available.
Severe renal impairment
Moderate or severe hepatic impairment
History of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi dysfunction, or abdominal adhesions
Patients currently experiencing or frequently experience diarrhea
The most common adverse effects, occurring in 5%- 15% of patients, were headache, abdominal pain, diarrhea, nausea, flatulence, and back pain.
Tegaserod is a 5-HT4 agonist that has demonstrated efficacy in the short-term treatment of women with IBS whose primary bowel symptom is constipation. Tegaserod is a prokinetic agent that enhances motility throughout the GI tract, reducing the abdominal pain, bloating, and constipation associated with constipation- predominant IBS. Clinical studies have shown that the proportion of patients responding to tegaserod are greater at month one than month three, suggesting that efficacy may decrease over time. Efficacy beyond 12 weeks has not been studied. Novartis is also planning to study its potential use for GERD, chronic constipation, and functional dyspepsia.
Published September 2002. Content based on medical literature and product information available at that time.
P&T Portfolio - Zelnorm.