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boxed warning
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 [see Indications and Usage ( 1 )] . 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 [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.1 ), ( 5.2 )]. WARNING: SERIOUS GASTROINTESTINAL ADVERSE REACTIONS See full prescribing information for complete boxed warning. 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. ( 1 ) Discontinue LOTRONEX immediately in patients who develop constipation or symptoms of ischemic colitis. Do not resume LOTRONEX in patients who develop ischemic colitis. ( 2.1 , 5.1 , 5.2 )
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warnings and cautions
5 WARNINGS AND PRECAUTIONS Serious Complications of Constipation: May occur in some patients without warning. Includes 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. ( 5.1 ) Discontinue LOTRONEX immediately if constipation occurs. ( 5.1 ) 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). ( 5.2 ) Discontinue LOTRONEX immediately if signs of ischemic colitis occur, such as rectal bleeding, bloody diarrhea, or new or worsening abdominal pain. ( 5.2 ) 5.1 Serious Complications of Constipation Some patients have experienced serious complications of constipation without warning. Serious complications of constipation, including obstruction, ileus, impaction, toxic megacolon, and secondary bowel ischemia, have been reported with use of LOTRONEX during clinical trials. Complications of constipation have been reported with use of 1 mg twice daily and with lower doses. A dose response relationship has not been established for serious complications 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 addition, rare cases of perforation and death have been reported from postmarketing clinical practice. In some cases, complications of constipation required intestinal surgery, including colectomy. Patients who are elderly, debilitated, or taking additional medications that decrease gastrointestinal motility may be at greater risk for complications of constipation. LOTRONEX should be discontinued immediately in patients who develop constipation [see Boxed Warning ]. 5.2 Ischemic Colitis Some patients have experienced ischemic colitis without warning. Ischemic colitis has been reported in patients receiving LOTRONEX in clinical trials as well as during marketed use of the drug. 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)...
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adverse reactions
6 ADVERSE REACTIONS The following adverse reactions are described in more detail in other sections of the label: Complications of constipation [see Boxed Warning , Warnings and Precautions ( 5.1 )] Ischemic colitis [see Boxed Warning , Warnings and Precautions ( 5.2 )] Most common adverse reactions (incidence >2% and >placebo) in clinical studies were constipation, abdominal discomfort and pain, nausea, and gastrointestinal discomfort and pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sebela at 1-844-732-3521 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Patients with Irritable Bowel Syndrome: Table 1 summarizes adverse reactions from 22 repeat-dose studies in patients with IBS who were treated with 1 mg of LOTRONEX twice daily for 8 to 24 weeks. The adverse reactions in Table 1 were reported in 1% or more of patients who received LOTRONEX and occurred more frequently on LOTRONEX than on placebo. A statistically significant difference was observed for constipation in patients treated with LOTRONEX compared to placebo (p
adverse reactions table
Table 1. Adverse Reactions Reported in ≥1% of Patients with Irritable Bowel Syndrome and More Frequently on LOTRONEX 1 mg Twice Daily Than PlaceboLOTRONEXBody SystemPlacebo1 mg twice dailyAdverse Reaction(n = 2,363)(n = 8,328)GastrointestinalConstipation6%29%Abdominal discomfort and pain4%7%Nausea5%6%Gastrointestinal discomfort and pain3%5%Abdominal distention1%2%Regurgitation and reflux2%2%Hemorrhoids1%2%