Important Safety Information

Please review the following important safety links as serious adverse events have been reported with the use of LOTRONEX:

>> Warnings
>> Contraindications
>> Tolerability and Safety Profile

Warnings

Infrequent but serious gastrointestinal adverse events have been reported with the use of LOTRONEX. These events, including ischemic colitis and serious complications of constipation, have resulted in hospitalization, and rarely, blood transfusion, surgery, and death.
The Prescribing Program for LOTRONEX^TM was implemented to help reduce risks of serious gastrointestinal adverse events. Only physicians who have enrolled in Prescribing Program for LOTRONEX, based on their understanding of the benefits and risks, should prescribe LOTRONEX.
LOTRONEX is indicated only for women with severe diarrhea-predominant IBS who have not responded adequately to conventional therapy. Before receiving the initial prescription for LOTRONEX, the patient must read and sign the Patient-Physician Agreement for LOTRONEX.
LOTRONEX should be discontinued immediately in patients who develop constipation or symptoms of ischemic colitis. Patients should immediately report constipation or symptoms of ischemic colitis to their physician. LOTRONEX should not be resumed in patients who develop ischemic colitis. Patients who have constipation should immediately contact their physician if the constipation does not resolve after LOTRONEX is discontinued. Patients with resolved constipation should resume LOTRONEX only on the advice of their treating physician.
In IBS clinical trials, approximately 10% of patients on LOTRONEX withdrew prematurely because of constipation. The incidence of serious complications of constipation was approximately 0.1% (1 per 1,000 patients) in women receiving either LOTRONEX or placebo.
In IBS clinical trials, the cumulative incidence of ischemic colitis in women receiving LOTRONEX was 0.2% (2 per 1,000 patients, 95% confidence interval 1 to 3) through 3 months and was 0.3% (3 per 1,000 patients, 95% confidence interval 1 to 4) through 6 months. Ischemic colitis was not reported in women receiving placebo.
The patient experience in controlled clinical trials is insufficient to estimate the incidence of ischemic colitis in patients taking LOTRONEX for longer than 6 months.

Contraindications
Please review the following important safety information before prescribing LOTRONEX:

LOTRONEX should not be initiated in patients with constipation.

LOTRONEX is contraindicated in patients with a history of the following:

chronic or severe constipation or sequelae from constipation
intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation and/or adhesions
ischemic colitis, impaired intestinal circulation, thrombophlebitis, or hypercoagulable state
Crohn's disease or ulcerative colitis
diverticulitis
severe hepatic impairment
hypersensitivity to any component of the product

LOTRONEX should not be used by patients who are unable to understand or comply with the Patient-Physician Agreement for LOTRONEX.

Concomitant administration of alosetron with fluvoxamine is contraindicated. Fluvoxamine, a known strong inhibitor of CYP1A2, has been shown to increase mean alosetron plasma concentrations (AUC) approximately 6-fold and prolong the half-life by approximately 3-fold.

Tolerability and Safety Profile
Please review the following important safety information before prescribing LOTRONEX:
Adverse events reported in IBS clinical trials.

Adverse events reported in ≥1% of IBS patients and more frequently on LOTRONEX
1 mg BID than placebo.

The incidence of constipation for patients with LOTRONEX 0.5 mg twice daily was 11% (n=243); 4% of patients withdrew from clinical studies due to constipation.

Please consult the Complete Prescribing Information.