Tegaserod is an agonist of serotonin type-4 (5-HT4) receptors that stimulates the peristaltic reflex and intestinal secretion, inhibits visceral sensitivity, enhances basal motor activity, and normalizes impaired motility throughout the gastrointestinal tract. Based on in vitro binding affinity and functional assessment, at clinically relevant plasma concentrations, tegaserod is an antagonist at 5-HT2B receptors in humans. It is expected to have minimal binding to 5-HT1 receptors. Tegaserod has no affinity for 5-HT3 or dopamine receptors. The main metabolite, M29, has negligible affinity for 5-HT4 receptors in vitro. In vivo studies showed that tegaserod enhanced basal motor activity and normalized impaired motility throughout the gastrointestinal tract. In addition, studies demonstrated that tegaserod moderated visceral sensitivity during colorectal distension in animals.

ZELNORM is a serotonin-4 (5-HT4) receptor agonist indicated for the treatment of adult women less than 65 years of age with irritable bowel syndrome with constipation (IBS-C). Limitations of Use:
• The safety and effectiveness of ZELNORM in men with IBS-C have not been established

The recommended dosage in adult women less than 65 years of age is 6 mg taken twice daily orally at least 30 minutes before meals. Discontinue ZELNORM in patients who have not had adequate control of symptoms after 4 to 6 weeks of treatment.

Most common adverse reactions (>2%) are headache, abdominal pain, nausea, diarrhea, flatulence, dyspepsia, and dizziness.

ZELNORM is contraindicated in patients with:
• A history of myocardial infarction, stroke, transient ischemic attack, or angina.
• A history of ischemic colitis or other forms of intestinal ischemia.
• Severe renal impairment (eGFR< 15 mL/min/1.73 m2 ) or end-stage renal disease.
• Moderate or severe hepatic impairment (Child-Pugh B or C).
• A history of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi dysfunction, or abdominal adhesions.
• Hypersensitivity to tegaserod.

• Cardiovascular Ischemic Events, Including Major Adverse Cardiovascular Events (MACE): The potential risks of treatment must be balanced with expectations in improvements in symptoms of IBS-C. Discontinue ZELNORM treatment in patients who experience a myocardial infarction, stroke, transient ischemic attack or angina. Evaluate the risks and benefits of continued treatment in patients who develop clinical or other evidence of cardiovascular ischemic heart disease and/or experience changes in health status that could increase cardiovascular risk during treatment.
• Ischemic Colitis: Monitor for rectal bleeding, bloody diarrhea, and new or worsening abdominal pain and discontinue ZELNORM if symptoms develop.
• Volume Depletion Associated with Diarrhea: Avoid use in patients with severe diarrhea. Instruct patients to discontinue ZELNORM and contact their healthcare provider if severe diarrhea, hypotension or syncope occur. See package insert for complete information.