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Pronunciation: a-LOE-se-tron HYE-droe-KLOR-ide
Class: 5-HT 3 receptor antagonist
- Tablets 0.5 mg
- Tablets 1 mg
Potent and selective serotonin (5-HT 3 ) antagonist that inhibits serotonin receptors in the GI tract.
Rapidly absorbed. T max is 1 h; C max is about 5 ng/mL (men) and about 9 ng/mL (women). Bioavailability is about 50% to 60%. Food decreases absorption about 25% and increases T max 15 min.
Vd is about 65 to 95 L; 82% protein bound.
Extensively metabolized by CYP2C9 (30%), CYP3A4 (18%), CYP1A2 (10%), and non–CYP-mediated phase I metabolic conversion (11%).
The half-life is about 1.5 h. Plasma Cl is about 600 mL/min. Renal Cl is about 112 mL/min. About 74% is excreted in the urine and 11% in the feces (1% as unchanged drug).
Special PopulationsRenal Function Impairment
Renal impairment (CrCl 4 to 56 mL/min) has no effect on renal elimination. The effect of renal impairment on the pharmacokinetics of alosetron metabolites has not been studied.Hepatic Function Impairment
Exposure to alosetron is increased.Elderly
Plasma levels are elevated by about 40% in patients 65 yr of age and older.Gender
Plasma concentrations are 30% to 50% lower and less variable in men.
Indications and Usage
Treatment of women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have chronic IBS symptoms (generally lasting at least 6 mo), who have had anatomic or biochemical abnormalities of the GI tract excluded, and who have not responded to conventional therapy.
History of chronic or severe constipation or sequelae from constipation; history of intestinal obstruction, stricture, toxic megacolon, GI perforation, or adhesions; history of ischemic colitis; history of Crohn disease or ulcerative colitis, impaired intestinal circulation, thrombophlebitis, hypercoagulable state, or active diverticulitis; history of severe hepatic impairment; coadministration of fluvoxamine. Do not initiate therapy in patients with constipation. Do not prescribe to patients who are unable to understand or comply with the patient-physician agreement.
Dosage and AdministrationAdults
PO Start with 0.5 mg twice daily. If constipation occurs after starting treatment at 0.5 twice daily, discontinue alosetron until constipation resolves. Treatment may be restarted at 0.5 mg once daily. If constipation recurs, immediately discontinue alosetron. Patients well controlled on 0.5 mg once or twice daily may be maintained on this dose. If after 4 weeks the dosage is well tolerated but does not adequately control IBS symptoms, the dosage may be increased to 1 mg twice daily. Discontinue treatment in patients who have not had adequate control of IBS symptoms after 4 weeks of treatment with 1 mg twice daily.
- Administer without regard to meals. Administer with food if GI upset occurs.
Store at 59° to 86°F. Protect from light and moisture.
Coadministration is contraindicated.Moderate CYP1A2 inhibitors (eg, cimetidine, quinolone antibiotics [eg, ciprofloxacin])
Has not been evaluated but should be avoided unless administration is clinically necessary.Strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, ketoconazole, protease inhibitors [eg, ritonavir], telithromycin, voriconazole)
Alosetron plasma concentrations may be elevated, increasing the pharmacologic effects and adverse reactions.
Laboratory Test Interactions
None well documented.
Constipation (29%); abdominal discomfort and pain (7%); nausea (6%); GI discomfort and pain (5%); diarrhea, flatulence, hemorrhoidal hemorrhage, hemorrhoids, upper abdominal pain (3%); abdominal distention, regurgitation and reflux (2%); impaction, perforation, small bowel mesenteric ischemia, ulceration (postmarketing).
Cough, nasopharyngitis, sinusitis, upper respiratory tract infection, UTI, viral gastroenteritis (3% or more); elevated ALT (1%).
Serious adverse reactions have been reported with use, including ischemic colitis and serious complications of constipation, which have resulted in hospitalization, blood transfusions, surgery, and death.Restricted prescribing program
Can only be prescribed by physicians enrolled in the prescribing program and only for women who have severe diarrhea-predominant IBS refractory to conventional therapy who have signed the Patient-Physician Agreement .
Discontinue immediately upon signs of constipation or symptoms of ischemic colitis. Do not resume therapy in patients who develop ischemic colitis.
Assess IBS symptoms prior to starting therapy and periodically during therapy. Frequently assess patient for alosetron-induced GI adverse reactions during treatment.
Category B .
Safety and efficacy not established.
May be at higher risk of constipation.
Renal function impairment (CrCl 4 to 56 mL/min) has no effect on alosetron renal elimination.
Use with caution in patients with mild to moderate hepatic function impairment. Exposure to alosetron is likely to be increased. Use is contraindicated in patients with severe hepatic function impairment.
Special Risk Patients
Debilitated patients and patients taking additional medications that decrease GI motility may be at greater risk of serious complications of constipation; use with caution.
Serious complications of constipation have been reported. Discontinue use immediately in patients who develop constipation. Do not use in patients who are constipated.
Has been reported. Discontinue immediately in patients with signs or symptoms of ischemic colitis (eg, bloody diarrhea, new or worsening abdominal pain, rectal bleeding).
Physicians must be enrolled in prescribing program for alosetron. Patients must sign Patient-Physician Agreement . Program stickers must be affixed to all prescriptions.
Doses as large as 16 mg (8 times the recommended total daily dose) have been administered without adverse reactions.
- Instruct patient to read the Medication Guide before starting therapy and to read and check for new information each time the medication is refilled.
- Review Patient-Physician Agreement , answer all questions, and give copy of signed agreement to patient.
- Caution patients not to start therapy with alosetron if they are constipated.
- Advise patient that medication is started at one 0.5 mg tablet twice daily for 4 wk and then may be increased by health care provider to one 1 mg tablet twice daily if needed for improved symptom control and if no adverse reactions have been noted. Caution patient not to change the dose unless advised by health care provider.
- Advise patient to take prescribed dose without regard to meals but to take with food if stomach upset occurs.
- Instruct patient to discontinue use and contact health care provider if IBS symptoms have not been controlled after 4 wk of therapy on the 1 mg twice-daily dosage.
- Instruct patient to stop using and contact health care provider immediately if any of the following occur: bloody diarrhea, constipation, new or worsening stomach pain, rectal bleeding. Advise patient to notify health care provider again if constipation does not resolve after stopping alosetron.
- Warn patient that if medication has been stopped because of intestinal adverse reactions not to restart medication unless advised by health care provider.
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