With better control of severe D-IBS symptoms, your pateints may have less interference with social activities

Your Patients And Severe D-IBS

The following sections will help you answer your patients' questions about severe D-IBS and LOTRONEX^®:

Who Is an Appropriate Candidate?

LOTRONEX is indicated only for women with severe D-IBS.

LOTRONEX is indicated only for women with severe diarrhea-predominant irritable bowel syndrome who have:

Chronic IBS symptoms (generally lasting 6 months or longer),
Had anatomic or biochemical abnormalities of the gastrointestinal tract excluded, and
Not responded adequately to conventional therapy.

Diarrhea-predominant IBS is severe if it includes diarrhea and one or more of the following:

Frequent and severe abdominal pain/discomfort
Frequent bowel urgency or fecal incontinence
Disability or restriction of daily activities due to IBS

Because of infrequent but serious gastrointestinal adverse events associated with LOTRONEX, the indication is restricted to those patients for whom the benefit-to-risk balance is most favorable. Clinical studies have not been performed to adequately confirm the benefits of LOTRONEX in men.

PEDIATRIC USE: Safety and effectiveness have not been established in pediatric patients.

Information for Pharmacists

LOTRONEX may be dispensed only on presentation of a prescription for LOTRONEX with a sticker for the Prescribing Program for LOTRONEX attached. A Medication Guide for LOTRONEX must be given to the patient each time LOTRONEX is dispensed as required by law. No telephone, facsimile, or computerized prescriptions are permitted with this program. Refills are permitted to be written on prescriptions.

Please consult the Medication Guide.

Drug Interactions

Because alosetron is metabolized by a variety of hepatic CYP drug-metabolizing enzymes, inducers or inhibitors of these enzymes may change the clearance of alosetron.
Fluvoxamine is a known strong inhibitor of CYP1A2 and also inhibits CYP3A4, CYP2C9, and CYP2C19. Concomitant administration of alosetron and fluvoxamine is contraindicated.
Concomitant administration of alosetron and moderate CYP1A2 inhibitors, including quinolone antibiotics and cimetidine should be avoided unless clinically necessary because of similar potential drug interactions.
Ketoconazole is a known strong inhibitor of CYP3A4. Caution should be used when alosetron and ketoconazole are administered concomitantly. Coadministration of alosetron and strong CYP3A4 inhibitors, such as clarithromycin, telithromycin, protease inhibitors, voriconazole, and itraconazole should be undertaken with caution because of similar potential drug interactions.
Although not studied, concomitant administration of alosetron with drugs such as isoniazid, procainamide, and hydralazine may have clinically relevant consequences.
The effect on CYP1A2 was explored in a clinical interaction study with theophylline and no effect was observed.
Alosetron had no clinically significant effect on plasma concentrations of the oral contraceptive agents ethinyl estradiol and levonorgestrel (CYP3A4 substrates).
The effects of alosetron on monoamine oxidases and on intestinal first pass secondary to high intraluminal concentrations have not been examined.
Alosetron does not appear to induce the major cytochrome P450 (CYP) drug metabolizing enzyme 3A. Alosetron also does not appear to induce CYP enzymes 2E1 or 2C19. It is not known whether alosetron might induce other enzymes.

IMPORTANT SAFETY INFORMATION: 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. Some patients have experienced serious complications of constipation or ischemic colitis without warning. 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.

LOTRONEX should be discontinued immediately in patients who develop constipation or symptoms of ischemic colitis such as rectal bleeding, bloody diarrhea or new or worsening abdominal pain. 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.

LOTRONEX should not be initiated in IBS patients who are constipated. LOTRONEX is contraindicated in patients with a history of chronic or severe constipation or a history of sequelae from constipation; with a history of intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation, and/or adhesions; with a history of ischemic colitis, impaired intestinal circulation, thrombophlebitis, or hypercoagulable state; with current or a history of Crohn's disease or ulcerative colitis; with severe hepatic impairment; with active diverticulitis or a history of diverticulitis; in patients who are unable to understand or comply with the Patient-Physician Agreement; and/or in patients with known hypersensitivity to any component of the product. Concomitant administration of alosetron with fluvoxamine is contraindicated.

Please consult the Complete Prescribing Information.