Instruct patients to stop LINZESS if severe diarrhea occurs and to contact their healthcare provider, who should consider dose suspension [see Patient Counseling Information (17)].

66 ADVERSE REACTIONS

6.16.1 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

During clinical development, approximately 2570, 2040, and 1220 patients with either IBS-C or CIC were treated with LINZESS for 6 months or longer, 1 year or longer, and 18 months or longer, respectively (not mutually exclusive).

Irritable Bowel Syndrome with Constipation (IBS-C)

Most Common Adverse Reactions

The data described below reflect exposure to LINZESS in the two placebo-controlled clinical trials involving 1605 adult patients with IBS-C (Trials 1 and 2). Patients were randomized to receive placebo or 290 mcg LINZESS once daily on an empty stomach for up to 26 weeks. Demographic characteristics were comparable between treatment groups [see Clinical Studies (14.1)]. Table 1 provides the incidence of adverse reactions reported in at least 2% of IBS-C patients in the LINZESS treatment group and at an incidence that was greater than in the placebo group.

Table 1: Adverse Reactions Reported in at least 2% of LINZESS-treated Patients and at an Incidence Greater than in Placebo Group Patients in the Two Phase 3 Placebo-controlled Trials (1 and 2) in IBS-C  a: “Abdominal pain” term includes abdominal pain, upper abdominal pain, and lower abdominal pain.
 
Adverse Reactions
 LINZESS
290 mcg
[N=807]
% 
Placebo
[N=798]
% 
Gastrointestinal
     Diarrhea
     Abdominal paina
     Flatulence
     Abdominal distension 
20
7
4
2 
3
5
2
1 
Infections and Infestations
     Viral Gastroenteritis 
3 
1 
Nervous System Disorders
     Headache 
4 
3 

Diarrhea

Diarrhea was the most commonly reported adverse reaction of the LINZESS-treated patients in the pooled IBS-C pivotal placebo-controlled trials. In these trials, 20% of LINZESS-treated patients reported diarrhea compared to 3% of placebo-treated patients. Severe diarrhea was reported in 2% of the LINZESS-treated patients versus less than 1% of the placebo-treated patients, and 5% of LINZESS-treated patients discontinued due to diarrhea vs less than 1% of placebo-treated patients. The majority of reported cases of diarrhea started within the first 2 weeks of LINZESS treatment. Fecal incontinence and dehydration were each reported in less than or equal to 1% of patients in the LINZESS treatment group [see Warnings and Precautions (5.2)].

Adverse Reactions Leading to Discontinuation

In placebo-controlled trials in patients with IBS-C, 9% of patients treated with LINZESS and 3% of patients treated with placebo discontinued prematurely due to adverse reactions. In the LINZ