Prescribing Information | Lotronex REMS Program | Patient Site

For women who have not responded adequately to conventional therapy for severe IBS-D

When her IBS-D symptoms keep closing in...Consider another path.

For appropriate patients, see what LOTRONEX can offer

In a retrospective analysis of two 12-week studies, women taking LOTRONEX reported significantly greater improvements in specific daily activities compared to those receive placebo.¹

Social Functioning	Working	Energy	Eating	Sleeping
Significantly improved social functioning versus placebo.	Significantly less interference with work or main activities versus placebo.	Significantly more energy versus placebo.	Significantly fewer eating problems versus placebo.	Significantly less difficult sleeping versus placebo.

*All P-values ≤0.032.

From a retrospective analysis of two 12-week studies. Data obtained from questionnaires at Week 12, against baseline. Changes in specific daily activities were evaluated in subpopulations (Study 1: N=291; Study 2: N=301) of women with severe IBS-D (severe defined as urgency on at least 10 of 14 days during screening) treated with either LOTRONEX or placebo. Change in the impact of IBS symptoms and problems in women who received LOTRONEX were not statistically different from those reported by women on placebo with regard to emotional and mental distress and physical and sexual activity.

Reference: 1. Data on file. Sebela Pharmaceuticals Inc.

Percent of patients reporting moderate or substantial improvement
	Lotronex (n=419)	Placebo (n=292)
Week 4	63%*	42%
Week 8	67%*	42%
Week 12	70%*	45%

INDICATIONS AND USAGE

LOTRONEX is indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS) 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 reactions 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.

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS GASTROINTESTINAL ADVERSE REACTIONS

Infrequent but serious gastrointestinal adverse reactions 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.

LOTRONEX is indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have not responded adequately to conventional therapy.
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 prescriber. LOTRONEX should not be resumed in patients who develop ischemic colitis. Patients who have constipation should immediately contact their prescriber if the constipation does not resolve after LOTRONEX is discontinued. Patients with resolved constipation should resume LOTRONEX only on the advice of their treating prescriber.

CONTRAINDICATIONS

Do not initiate in patients with constipation
History of 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
Concomitant use of fluvoxamine

WARNINGS AND PRECAUTIONS

Serious Complications of Constipation: May occur in some patients without warning. Include obstruction, ileus, impaction, toxic megacolon, and secondary bowel ischemia and in rare cases perforation and death have been reported. Risk is increased in patients who are elderly, debilitated, or taking medications that decrease bowel motility. The incidence of serious complications of constipation was approximately 0.1% (1 per 1,000 patients) in women receiving either LOTRONEX or placebo.
Discontinue LOTRONEX immediately if constipation occurs.
Ischemic colitis: May occur in some patients without warning. Promptly evaluate patients with signs of ischemic colitis (e.g., rectal bleeding, bloody diarrhea, new or worsening abdominal pain). 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.
Discontinue LOTRONEX immediately if signs of ischemic colitis occur, such as rectal bleeding, bloody diarrhea, or new or worsening abdominal pain.

ADVERSE REACTIONS

Most common adverse reactions (incidence >2% and >placebo) in clinical studies were constipation, abdominal discomfort and pain, nausea, and gastrointestinal discomfort and pain.

Please see the accompanying complete prescribing information for LOTRONEX, including Boxed Warning and Medication Guide.