5-HT₃ Receptor Antagonist

Treatment of irritable bowel syndrome (IBS) in women whose predominant bowel symptom is diarrhea; use in males with IBS has not been substantiated

B

No adequate and well-controlled studies have been done in pregnant women. Alosetron should be used in pregnant women only if clearly needed. Animal studies indicate that alosetron and/or metabolites are excreted in breast milk. It is not known if alosetron in excreted in human milk. Caution should be used in administering alosetron to a nursing woman.

Hypersensitivity to alosetron or any component

Constipation is a frequent, dose-related side effect. Patients who have not had a bowel movement in 3-4 days should be instructed to hold therapy until bowel movements resume. Acute ischemic colitis has been reported during alosetron treatment. Discontinue in patients who experience rectal bleeding or a sudden worsening of abdominal pain. Use with caution in patients with a history of bowel obstruction. Safety and efficacy have not been established in pediatric or male patients.

>10%: Gastrointestinal: Constipation (28%)

1% to 10%:

Central nervous system: Sleep disorders (3%), depression (2%)

Cardiovascular: Hypertension (2%)

Gastrointestinal: Nausea (7%), gastrointestinal discomfort and pain (5%), abdominal discomfort and pain (5%), gastrointestinal gaseous symptoms (3%), viral infections (2%), dyspepsia (3%), abdominal distention (2%), hemorrhoids (2%)

Otic: Bacterial ear infection (1%)

Respiratory: Allergic rhinitis (2%); throat and tonsil discomfort and pain (1%); bacterial ear, nose and throat infection (1%)

<1%: Elevated hepatic transaminases (0.5%), acute ischemic colitis, arrhythmias, contusions, hematomas, photophobia, proctitis, abnormal bilirubin levels, breathing disorders, cough, sedation and abnormal dreams, allergies, allergic reactions, unusual odors and taste, anxiety, menstrual disorders, sexual function disorders, acne, folliculitis, urinary infections, polyuria, diuresis

Case report: Hepatitis

There is not a specific antidote for overdose; manage with appropriate supportive therapy

CYP2C9, CYP3A4, and CYP1A2 enzyme substrate; inhibits CYP1A2, 2E1 only at extremely high concentrations (no clinical significance)

Store at 15°C to 30°C (59°F to 86°F)

Alosetron is a potent and selective antagonist of a subtype of the serotonin receptor, 5-HT₃ receptor. 5-HT₃ receptors are extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels affect the regulation of visceral pain, colonic transit, and gastrointestinal secretions. In patients with irritable bowel syndrome, improvement in pain, abdominal discomfort, urgency, and diarrhea may occur.

Distribution: V_d: 65-95 L

Protein binding: 82%

Metabolism: Extensive hepatic metabolism. Alosetron is metabolized by CYP2C9, 3A4, and 1A2. Thirteen metabolites have been detected in the urine. Biological activity of these metabolites in unknown.

Bioavailability: Mean: 50% to 60% (range: 30% to >90%)

Half-life: 1.5 hours for alosetron

Time to peak: 1 hour after oral administration

Elimination: Urine (73%) and feces (24%); 7% is recovered as unchanged drug (1% in the feces and 6% in the urine)

Adults: Female: Oral: 1 mg twice daily with or without food. Patients who experience constipation may need to interrupt therapy.

Dosage adjustment in renal impairment: No dosage adjustment is recommended for patients with Cl_cr 4-56 mL/minute; use in Cl_cr <4 mL/minute or hemodialysis patients has not been studied

Dosage adjustment in hepatic impairment: Specific guidelines are not available

Elderly: Dosage adjustment is not required

Take with or without food

No information available to require special precautions

No effects or complications reported

Take with or without food. Do not take if you are frequently constipated; constipation is a common side effect. Call your healthcare provider if you do not have a bowel movement for 3-4 days. If you have sudden worsening of abdominal pain or blood in your stool call your healthcare provider immediately. Notify your healthcare provider if you are pregnant, plan on becoming pregnant, or if you are breast-feeding.

Monitor for improvement in cramping abdominal pain, abdominal discomfort, urgency and diarrhea

Tablet: 1 mg