Tegaserod

Tegaserod tablet is indicated for the treatment of adult women less than 65 years of age with irritable bowel syndrome with constipation (IBS-C).

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.

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

Pediatric Use: Safety and effectiveness of Tegaserod in pediatric patients have not been established.

Geriatric Use: Tegaserod is not indicated in patients 65 years of age and older.

Renal Impairment: Tegaserod is contraindicated in patients with severe renal impairment (eGFR <15 mL/min/1.73 m2) or end stage renal disease.

Hepatic Impairment: Tegaserod is contraindicated in patients with moderate or severe hepatic impairment.

Patient should be advised to take Tegaserod (6 mg twice daily) 30 minutes before meal.

Patient should also be made aware of the possible occurrence of diarrhea during therapy. In most cases, the diarrhea occurred early, is transient, is most often observed as a single episode during the 12 week treatment period, and resolved with continued therapy.

Patients should be instructed to consult their physician if they experience new or worsening abdominal pain not typical of their IBS symptoms.

No clinically relevant drug-drug interactions have been observed with dextromethorphan, theophylline, digoxin, oral contraceptives, and warfarin.

Tegaserod is contraindicated in patients with:

• A history of myocardial infarction (MI), stroke, transient ischemic attack (TIA), 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 and severe hepatic impairment
• A history of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi dysfunction, or abdominal adhesions
• Hypersensitivity to tegaserod.

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

Available data from case reports with Tegaserod use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are no data regarding the presence of tegaserod in human milk, the effects on the breastfed infant, or the effects on milk production. Tegaserod and its metabolites are present in rat milk; the milk to plasma concentration ratio for tegaserod is very high.

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 Tegaserod 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 Tegaserod if symptoms develop.

Volume Depletion Associated with Diarrhea: Avoid use in patients with severe diarrhea. Instruct patients to discontinue Tegaserod and contact their healthcare provider if severe diarrhea, hypotension or syncope occur.

Suicidal Ideation and Behavior: Monitor patients for clinical worsening of depression and emergence of suicidal thoughts and behaviors, especially during the initial few months of treatment. Instruct patients to immediately discontinue Tegaserod and contact their healthcare provider if their depression is persistently worse or they are experiencing emergent suicidal thoughts or behaviors.

Drugs for Irritable Bowel Syndrome

Store at a cool and dry place, protected from light and moisture.