tegaserod (Rx)

>10%

Headache (14%)

Abdominal pain (11%)

1-10%

Nausea (8%)

Diarrhea (8%)

Flatulence (6%)

Dyspepsia (4%)

Dizziness (4%)

Anemia (<2%)

Vertigo (<2%)

Rectal hemorrhage (<2%)

Asthenia (<2%)

Increased CPK (<2%)

Increased appetite (<2%)

Arthropathy (<2%)

Tendonitis (<2%)

Migraine (<2%)

<1%

Cardiovascular (CV) ischemic events (0.06-0.1%)

Suicidal ideation/behavior (0.08%)

Major adverse cardiac events (MACE), overall population (0.03-0.06%)

MACE, female population (0.01-0.03%)

Postmarketing Reports

Ischemic colitis, mesenteric ischemia, gangrenous bowel, and rectal bleeding

Severe diarrhea resulting in syncope, hypotension, hypovolemia, electrolyte disorders

Sphincter of Oddi spasm; bile duct stone; cholecystitis with elevated transaminases; elevation in ALT, AST, and bilirubin; hepatitis

Alopecia

Hypersensitivity reactions, including anaphylaxis

Contraindications

History of myocardial infarction (MI), stroke, transient ischemic attack (TIA), or angina

History of ischemic colitis or other forms of intestinal ischemia

Severe renal impairment (eGFR <15 mL/min/1.73 m²) or ESRD

Moderate and severe hepatic impairment (Child-Pugh B or C)

History of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi dysfunction, or abdominal adhesions

Hypersensitivity

Cautions

Stroke, MI, and CV death (MACE) have been reported in adults who had an increased CV risk based on their medical history; contraindicated with history of MI, stroke, TIA, or angina; assess women aged <65 yr for a history of CV disease/risk factors before initiating; discontinue if MI, stroke, TIA, or angina occurs

Ischemic colitis and other forms of intestinal ischemia reported, including cases requiring hospitalization; discontinue if symptoms develop, such as rectal bleeding, bloody diarrhea, or new or worsening abdominal pain

Diarrhea commonly occurs; may result in rare, but serious consequences, including hypovolemia, hypotension, and syncope; avoid use with current or frequently occurring diarrhea

Suicide, suicidal attempt and ideation, and self-injurious behavior reported in clinical trials of IBS-C and other gastrointestinal motility disorders; frequency of suicidal ideation or attempts with tegaserod treatment (8 of 10,003 patients) was higher than with placebo (1 of 5,425 patients) and more frequent among patients receiving antidepressants; monitor for worsening depression and emergence of suicidal thoughts and behaviors; instruct patients to discontinue immediately and contact their physician if symptoms emerge or worsen

Pregnancy

Available data from case reports with use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Animal studies

• Decreased survival of rat pups observed with maternal dietary administration of tegaserod at 71 times the recommended dose during organogenesis and through lactation
• Decreased body weight and delays in developmental landmarks in rat pups were observed with maternal dietary administration of 45 times the recommended dose

Lactation

There are no data regarding the presence in human milk, effects on breastfed infants, or on milk production

Tegaserod and its metabolites are present in rat milk; the milk-to-plasma concentration ratio for tegaserod is very high

When a drug is present in animal milk, it is likely that the drug will be present in human milk

Because of the potential for serious reactions in the breastfed infant, including tumorigenicity, advise lactating women not to breastfeed during tegaserod treatment

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Serotonin type-4 (5-hydroxytryptamine-4 [5-HT4]) receptor partial agonist

Stimulates the peristaltic reflex and intestinal secretion, inhibits visceral sensitivity, enhances basal motor activity, and normalizes impaired motility throughout the gastrointestinal tract

Absorption

Bioavailability: ~10% (fasting)

Peak plasma time: ~1 hr

Peak plasma concentration: 2.9 ng/mL

AUC: 10.5 h·ng/mL (single dose); increases proportionally at steady-state over dosage range

Food: Reduces peak plasma concentration by ~20-40% and AUC by 40-65%

Distribution

Vd: 368 L

Protein bound: 98%

Metabolism

Metabolized via hydrolysis and direct glucuronidation; undergoes hydrolysis in stomach followed by oxidation and conjugation, which produces the M29 metabolite (negligible affinity for 5-HT4)

Elimination

Half-life: 4.6-8.1 hr

Plasma clearance: 77 L/hr (IV administration)

Excretion: ~66% feces (unchanged); ~33% urine (as metabolites)

Oral Administration

Take at least 30 minutes before meals

Storage

Store at 20-25°C (68-77°F)

Protect from moisture