Adverse Reactions Leading to Dose Reductions

In the open-label, long-term trials, 2147 patients with IBS-C received 290 mcg of LINZESS daily for up to 18 months. In these trials, 29% of patients had their dose reduced or suspended secondary to adverse reactions, the majority of which were diarrhea or other GI adverse reactions.

Other Adverse Reactions

Adverse reactions that were reported in at least 1% and less than 2% of IBS-C patients in the LINZESS treatment group and at an incidence greater than in the placebo treatment group are listed below by body system:

Gastrointestinal Disorders: gastroesophageal reflux disease, vomiting

General Disorders and Administration Site Conditions: fatigue

Other Adverse Events

In placebo-controlled trials in patients with IBS-C, less than 1% LINZESS-treated patients and no placebo-treated patients reported hematochezia; no patient in either treatment group reported melena. Less than 1% of LINZESS-treated and placebo treated patients reported allergic reactions, urticaria, or hives as adverse events.

Chronic Idiopathic Constipation (CIC)

Most Common Adverse Reactions

The data described below reflect exposure to LINZESS in the two double-blind placebo-controlled clinical trials of 1275 adult patients with CIC (Trials 3 and 4). Patients were randomized to receive placebo or 145 mcg LINZESS or 290 mcg LINZESS once daily on an empty stomach, for at least 12 weeks. Demographic characteristics were comparable between both LINZESS treatment groups and placebo [see Clinical Studies (14.2)]. Only data for the recommended LINZESS 145 mcg dose and placebo are presented. Table 2 provides the incidence of adverse reactions reported in at least 2% of CIC patients in the 145 mcg LINZESS treatment group and at an incidence that was greater than in the placebo treatment group.

Table 2: Adverse Reactions Reported in at least 2% of 145 mcg LINZESS-treated Patients and at an Incidence Greater than in Placebo Group Patients in the Two Phase 3 Placebo-controlled Trials (3 and 4) in CIC  a: “Abdominal pain” term includes the abdominal pain, upper abdominal pain, and lower abdominal pain
 
Adverse Reactions LINZESS
145 mcg
[N=430]
% 
Placebo
[N=423]
% 
Gastrointestinal
     Diarrhea
     Abdominal paina
     Flatulence
     Abdominal distension 
16
7
6
3 
5
6
5
2 
Infections and Infestations
     Upper respiratory tract infection
     Sinusitis 
5
3 
4
2 

Diarrhea

Diarrhea was the most commonly reported adverse reaction of the LINZESS-treated patients in the two pooled placebo-controlled CIC trials. In these trials, 16% of LINZESS-treated patients reported diarrhea compared to 5% of placebo-treated patients. Severe diarrhea was reported in 2% of the 145 mcg 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