Tegaserod

• Irritable Bowel Syndrome with Constipation
• Functional Constipation
• Chronic Constipation

Tegaserod is a selective serotonin 5-HT4 receptor partial agonist that was re-approved with restrictions for treating irritable bowel syndrome with constipation (IBS-C) in women under 65 years of age who have not responded adequately to other therapies. It stimulates gastrointestinal motility and secretion.

Mechanism of Action

Tegaserod works through serotonin receptor activation in the GI tract:

• 5-HT4 receptor partial agonist: Binds to and activates 5-HT4 receptors in the enteric nervous system
• Stimulates peristaltic reflex: Triggers coordinated intestinal contractions
• Increases chloride secretion: Promotes fluid secretion into the intestinal lumen
• Accelerates GI transit: Speeds colonic and small intestinal transit times
• Reduces visceral sensitivity: May decrease abdominal pain perception

Available Formulations

Tegaserod is available as oral tablets:

• 6 mg tablets (Zelnorm)

Distribution is restricted through the Zelnorm REMS program due to cardiovascular safety concerns.

Medical Uses

FDA-Approved Indication:

• Treatment of IBS-C in women less than 65 years of age who have had an inadequate response to other therapies

This restricted indication reflects a careful benefit-risk assessment following cardiovascular safety concerns that led to its withdrawal in 2007 and subsequent re-approval in 2019.

Dosing Guidelines

Adults (Women <65 years with IBS-C):

• 6 mg orally twice daily, before meals
• Discontinue after 4-6 weeks if no response

Administration:

• Take shortly before meals
• Swallow tablets whole with water

Important Safety Information

Contraindications:

• History of myocardial infarction, stroke, TIA, or angina
• History of ischemic colitis or intestinal ischemia
• Severe renal impairment (CrCl <15 mL/min) or ESRD
• Moderate or severe hepatic impairment (Child-Pugh B or C)
• History of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi dysfunction, or abdominal adhesions
• Current or history of suicidal ideation or behavior

Warnings and Precautions:

• Cardiovascular ischemic events: Risk of myocardial infarction and stroke; only for women <65 without CV risk factors
• Ischemic colitis and intestinal ischemia: Discontinue immediately if symptoms develop
• Diarrhea: May be severe; can cause serious complications
• Suicidal ideation: Monitor for new or worsening depression

REMS Program Requirements:

• Prescribers must enroll and complete training
• Patients must sign acknowledgment form
• Dispensed only through certified pharmacies

Drug Interactions

• No significant CYP450 interactions: Tegaserod is not significantly metabolized by CYP enzymes
• Digoxin: May reduce digoxin levels by 15%; monitor if clinically indicated
• Antacids: No significant interaction
• Oral contraceptives: No significant interaction with ethinyl estradiol/levonorgestrel

Special Populations

• Age restriction: Only approved for women <65 years
• Sex restriction: Only approved for women (not men)
• Renal Impairment: Contraindicated in severe impairment (CrCl <15 mL/min)
• Hepatic Impairment: Contraindicated in moderate to severe impairment
• Pregnancy: Category B; use only if clearly needed
• Lactation: Unknown if excreted in breast milk; use with caution
• Cardiovascular disease: Contraindicated in patients with CV history or risk factors