Alosetron Hydrochloride

Trade Names:
Lotronex
- Tablets 0.5 mg (as base)
- Tablets 1 mg (as base)

Potent and selective serotonin (5о“Ñ‘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%). Biologic activity of metabolites is unknown.

The t Ð… is about 1.5 h. Plasma Cl is about 600 mL/min. Renal Cl is about 94 mL/min. About 73% is excreted in the urine, 24% in the feces (1% as unchanged drug), and 7% of dose is recovered as unchanged drug.

Renal function impairment (Ccr 4 to 56 mL/min) has no effect on renal elimination.

Plasma levels are elevated by about 40% in patients 65 yr of age and older.

Plasma concentrations are 30% to 50% lower and less variable in men.

Treatment of irritable bowel syndrome (IBS) in women whose predominant bowel syndrome is diarrhea.

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; current or history of Crohn disease or ulcerative colitis, impaired intestinal circulation, thrombophlebitis, or hypercoagulable state; active diverticulitis. Do not initiate therapy in patients with constipation (ie, fewer than 3 bowel movements a week, hard or lumpy stools, straining during bowel movement).

PO 0.5 mg twice daily initially. Increase dose to 1 mg twice daily after 4 wk if well tolerated but IBS symptoms not adequately controlled. Discontinue use after 4 wk of 1 mg twice-daily dosing if IBS symptoms are not adequately controlled.

• Administer without regard to meals. Administer with food if GI upset occurs.

Store tablets at controlled room temperature (59° to 86°F). Protect from light and moisture.

Because alosetron plasma levels may be increased, use with caution.

Alosetron plasma levels may be elevated, increasing the pharmacologic and adverse reactions.

None well documented.

Hypertension.

Headache (postmarketing).

Rash (postmarketing).

Constipation (29%); abdominal discomfort and pain (7%); nausea (6%); GI discomfort and pain (5%); abdominal distention, hemorrhoids, regurgitation and reflux (2%); ischemic colitis (less than 1%); ileus, impaction, obstruction, perforation, ulceration, small bowel mesenteric ischemia (postmarketing).

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.

Can only be prescribed by physicians enrolled in the prescribing program and only for women who have diarrhea-predominant IBS refractory to conventional therapy who have signed 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 .

Undetermined.

Safety and efficacy not established.

May be at higher risk of constipation.

Use with caution; increased exposure to alosetron is likely to occur in patients with hepatic function impairment.

Serious complications of constipation have been reported. Patients who are elderly, debilitated, or taking additional medications that decrease GI motility may be at higher risk for complications of constipation. 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 Lotronex . 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 that if a dose is missed to skip that dose and take the next dose at the regularly scheduled time. Caution patient to never take 2 doses to try to catch up.
• 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 dose.
• 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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