Usage
Tegaserod is indicated for the treatment of irritable bowel syndrome with constipation (IBS-C) in adult women younger than 65 years of age. It was previously indicated for chronic idiopathic constipation (CIC) in adults under 55. Tegaserod is classified as a serotonin-4 (5-HT4) receptor agonist, also known as a serotonergic neuroenteric modulator. It works by stimulating peristalsis, increasing intestinal fluid secretion, and potentially reducing visceral hypersensitivity in the gut.
Alternate Names
- Generic Name: Tegaserod maleate
- Brand Name: Zelnorm (no longer available in the U.S. except in limited emergency situations)
- Other Names: Zelmac, HTF 919, SDZ HTF-919.
How It Works
Pharmacodynamics: Tegaserod is a partial 5-HT4 receptor agonist. Stimulation of these receptors in the gastrointestinal tract enhances gastrointestinal motility, increases intestinal secretions, and may modulate visceral sensitivity.
Pharmacokinetics:
- Absorption: Well absorbed orally. Taking it with food can slightly reduce Cmax (maximum concentration) but does not affect overall exposure (AUC, area under the curve).
- Metabolism: Primarily metabolized by acid-catalyzed hydrolysis in the stomach followed by oxidation and conjugation, resulting in the main metabolite, 5-methoxyindole-3-carboxylic acid glucuronide (M 29.0), which is inactive. Direct glucuronidation is a minor pathway.
- Elimination: Primarily eliminated in feces (about two-thirds) and the rest in urine, mainly as M 29.0. Plasma clearance is around 77 L/h, with a terminal half-life of roughly 11 hours.
Dosage
Standard Dosage
Adults (Women < 65 years old):
- IBS-C: 6 mg orally twice daily, approximately 30 minutes before meals.
- Treatment should be discontinued if there is no adequate symptom control after 4-6 weeks.
Children:
- Not established. Safety and efficacy not determined.
Special Cases:
- Elderly Patients (≥65 years): Contraindicated.
- Patients with Renal Impairment: No dose adjustment needed for mild to moderate impairment. Contraindicated in severe renal impairment (eGFR < 15 mL/min/1.73 m²).
- Patients with Hepatic Dysfunction: No dose adjustment for mild to moderate dysfunction. Contraindicated in moderate or severe hepatic impairment (Child-Pugh Class B or C).
Clinical Use Cases
Tegaserod is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments may be considered in specific cases based on individual patient factors.
Side Effects
Common Side Effects
- Headache
- Diarrhea (often transient, occurring within the first week)
- Dizziness
- Abdominal pain
- Nausea
- Flatulence
Rare but Serious Side Effects
- Ischemic colitis (symptoms include rectal bleeding, bloody diarrhea, and new or worsening abdominal pain)
- Myocardial infarction (MI)
- Stroke
- Transient ischemic attack (TIA)
- Angina
Long-Term Effects
Long-term effects not well-established, as treatment duration is limited to a maximum of 12 weeks.
Adverse Drug Reactions (ADR)
Serious cardiovascular events (MI, stroke, TIA) and ischemic colitis.
Contraindications
- History of MI, stroke, TIA, or angina
- History of bowel obstruction, symptomatic gallbladder disease, sphincter of Oddi dysfunction, or abdominal adhesions
- History of ischemic colitis or other forms of intestinal ischemia
- Severe renal impairment or end-stage renal disease
- Moderate or severe hepatic impairment
- Hypersensitivity to tegaserod
- Diarrhea
- Age 65 or older
Drug Interactions
Limited clinically significant drug interactions are known. It may reduce the effectiveness of hormonal contraceptives. Concomitant use with drugs inhibiting P-glycoprotein (e.g., quinidine) may increase tegaserod exposure, but the clinical significance is unclear.
Pregnancy and Breastfeeding
- Pregnancy: Pregnancy Category B. While animal studies have shown some adverse effects at high doses, human data are limited. Use with caution if benefits outweigh risks.
- Breastfeeding: Not recommended. Tegaserod and/or metabolites are present in rat milk.
Drug Profile Summary
- Mechanism of Action: 5-HT4 receptor partial agonist stimulating gut motility and secretions.
- Side Effects: Headache, diarrhea, dizziness, abdominal pain, nausea. Serious: Ischemic colitis, MI, stroke.
- Contraindications: History of cardiovascular or intestinal ischemic events, severe renal/hepatic impairment, bowel obstruction. Age 65 or older.
- Drug Interactions: Limited clinical interactions.
- Pregnancy & Breastfeeding: Use with caution in pregnancy if benefits outweigh risks. Not recommended while breastfeeding.
- Dosage: 6 mg twice daily before meals for IBS-C (women <65 years). Max 12 weeks.
Popular Combinations
Not typically used in combination therapy.
Precautions
- Screen for contraindications.
- Monitor for cardiovascular and gastrointestinal side effects.
- Discontinue if symptoms of ischemic colitis or serious cardiovascular events occur.
- Be aware of the potential for suicidal thoughts and behavior.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Tegaserod?
A: For adult women under 65 with IBS-C, the recommended dose is 6 mg orally twice daily, 30 minutes before meals.
Q2: Can men take Tegaserod?
A: No, the safety and efficacy of Tegaserod have not been established in men.
Q3: How long can a patient take Tegaserod?
A: Treatment should not exceed 12 weeks. Discontinue if no response after 4-6 weeks.
Q4: What are the serious side effects to watch out for with Tegaserod?
A: Ischemic colitis (bloody diarrhea, new/worsening abdominal pain), serious cardiovascular events (chest pain, shortness of breath, weakness on one side of the body), and suicidal thoughts/behavior.
Q5: Is Tegaserod safe in pregnancy?
A: Pregnancy Category B. Limited human data. Use cautiously if benefits outweigh risks.
Q6: Can I breastfeed while taking Tegaserod?
A: Breastfeeding is not recommended.
Q7: What should I do if a patient experiences diarrhea while on Tegaserod?
A: Diarrhea is a common side effect, often occurring during the first week and resolving with continued treatment. However, if diarrhea is severe or associated with other symptoms like hypotension or syncope, the drug should be discontinued.
Q8: What if a patient has mild renal impairment?
A: No dose adjustment is needed for mild to moderate renal impairment.
Q9: Is Tegaserod available over-the-counter?
A: No, Tegaserod is available by prescription only, and only for emergency situations.
Q10: What is the mechanism of action of Tegaserod?
A: Tegaserod is a 5-HT4 receptor partial agonist. It acts by stimulating gut motility and secretions.
