Linzess is AbbVie's brand of linaclotide, a 14-amino-acid peptide that activates guanylate cyclase-C on the inner surface of the intestine. That switch pumps chloride and bicarbonate into the gut, water follows, and stool moves faster. FDA approved it on 30 August 2012 (Drugs@FDA, NDA 202811) and has approved efficacy supplements since, most recently on 12 June 2023, 4 November 2025 and 21 May 2026. The current label covers irritable bowel syndrome with constipation (IBS-C) in adults and children from 7, chronic idiopathic constipation (CIC) in adults, and functional constipation in children from 2.
Peptide Lexicon explains the molecule in its linaclotide entry. This page reports the side effects the label records, by indication and dose, with the dates. Nothing here is a recommendation; a change noticed on treatment is a question for the prescriber.
Why nearly every side effect is in the gut
The label's pharmacokinetics section is unusual: after 72, 145 or 290 mcg, neither linaclotide nor its active metabolite could be measured in plasma, so the usual figures (peak concentration, half-life, exposure) "cannot be calculated." The peptide is broken down inside the gut to smaller peptides and amino acids; only about 3% to 5% of the active peptide was recovered in stool.
That is the opposite of the problem most oral peptides have. On our oral peptides page the obstacle is getting a peptide past the gut wall; linaclotide works because it stays on the near side of it. The consequence for side effects is that the label tables are almost entirely diarrhoea, pain, gas and bloating, and the drug-interaction section reports no interaction studies because systemic exposure is negligible.
The numbers, by indication and dose
Every table below lists reactions reported in at least 2% of Linzess patients and more often than on placebo, from the label effective 21 May 2026.
Adults with IBS-C, 290 mcg, two trials of up to 26 weeks (Table 1)
| Reaction | Linzess 290 mcg (n = 807) | Placebo (n = 798) | Difference |
|---|---|---|---|
| Diarrhoea | 20% | 3% | +17 |
| Abdominal pain | 7% | 5% | +2 |
| Flatulence | 4% | 2% | +2 |
| Headache | 4% | 3% | +1 |
| Viral gastroenteritis | 3% | 1% | +2 |
| Abdominal distension | 2% | 1% | +1 |
A third IBS-C trial (614 patients, 12 weeks) reported reactions "similar to those in Table 1."
Adults with CIC, 145 mcg, two trials of at least 12 weeks (Table 2)
| Reaction | Linzess 145 mcg (n = 430) | Placebo (n = 423) | Difference |
|---|---|---|---|
| Diarrhoea | 16% | 5% | +11 |
| Abdominal pain | 7% | 6% | +1 |
| Flatulence | 6% | 5% | +1 |
| Upper respiratory tract infection | 5% | 4% | +1 |
| Sinusitis | 3% | 2% | +1 |
| Abdominal distension | 3% | 2% | +1 |
The 72 mcg dose (Trial 5, 1,223 CIC patients, 12 weeks)
| Reaction | 72 mcg (n = 411) | 145 mcg (n = 411) | Placebo (n = 401) |
|---|---|---|---|
| Diarrhoea | 19% | 22% | 7% |
| Abdominal distension | 2% | 1% | under 1% |
Trial 5 is the only head-to-head of two doses on the label, and it is the useful one for the question searchers ask most: halving the dose from 145 to 72 mcg moved diarrhoea from 22% to 19%, a 3-point difference, while placebo sat at 7%. Severe diarrhoea is where the lower dose separates more clearly — under 1% on 72 mcg against 2% on 145 mcg.
Children (Trials 7 and 8)
| Population | Dose | Diarrhoea on Linzess | On placebo |
|---|---|---|---|
| Functional constipation, 6–17 years (164 per group) | 72 mcg | 4% | 2% |
| IBS-C, 7–17 years (55 on 145 mcg) | 145 mcg | 7% | not stated in the label text |
| IBS-C, 7–17 years | 290 mcg (above the recommended paediatric dose) | 8% | — |
The paediatric rates are a fraction of the adult ones. The label states the paediatric safety profile was similar to the adults'; one child in each of the two trials had severe diarrhoea, and in the IBS-C trial that case was on a dose higher than recommended.
When diarrhoea starts, and how often people stopped
The label gives timing in one consistent sentence across every trial: the majority of reported diarrhoea began within the first two weeks. It does not publish how long episodes lasted.
| Measure | IBS-C, 290 mcg | CIC, 145 mcg | CIC, 72 mcg | Placebo |
|---|---|---|---|---|
| Severe diarrhoea | 2% | 2% | under 1% | under 1% |
| Stopped because of any adverse reaction | 9% | 5%–8% | 3% | under 1%–4% |
| Stopped because of diarrhoea | 5% | 3%–5% | 2% | under 1% |
Over longer use the figures grow. In open-label studies of up to 18 months on 290 mcg, 29% of 2,147 IBS-C patients and 27% of 1,129 CIC patients had their dose reduced or suspended for adverse reactions, mostly diarrhoea or other gut reactions. Those studies had no placebo arm, so the figure describes how often the dose was changed, not how many of the reactions the drug caused.
Severe diarrhoea, as the label words it
Warning 5.2 records that after approval, "severe diarrhea associated with dizziness, syncope, hypotension and electrolyte abnormalities (hypokalemia and hyponatremia) requiring hospitalization or intravenous fluid administration" has been reported. The label's instruction to prescribers is to suspend dosing and rehydrate the patient. The label also records that taking Linzess right after a high-fat breakfast produced looser and more frequent stools than taking it fasted, which is why the trials gave it at least 30 minutes before a meal.
The boxed warning, and how it has moved
The box reads: risk of serious dehydration in paediatric patients under 2 years. Its basis is animal data, stated in section 8.4: in neonatal mice (a human-age equivalent of about 0 to 28 days), linaclotide at 10 mcg/kg/day caused deaths on day 7, and tolerance rose with age — 2-week-old mice tolerated 50 mcg/kg/day but died after a single 100 mcg/kg dose; 3-week-old mice tolerated 100 mcg/kg/day but died after 600 mcg/kg. A clinical study of 99 children from 6 months to 17 years, measuring the drug's target receptor in gut biopsies, found no age trend from 2 upward and "insufficient data" below 2.
The warning used to cover far more children. Label versions on DailyMed dated 2018 read: contraindicated "in pediatric patients up to 6 years of age," with use to be avoided from 6 through 17 and no paediatric efficacy established. The current label contraindicates only under 2, and approves the drug for functional constipation from 2 and IBS-C from 7. The current label supports the paediatric approvals with the trials in children aged 2 to 17 and still sets out the mouse data in full; the mouse findings themselves did not change.
What FDA's reports show
openFDA's adverse event data (FAERS, updated 28 October 2026) returns 26,154 reports naming Linzess as a product, 8,991 of them flagged serious. The most frequent terms are diarrhoea (4,860), "drug ineffective" (4,532), off-label use (3,171), constipation (1,912), nausea (1,451), abdominal distension (1,193) and fatigue (1,133). A report is a suspicion sent to FDA, not a confirmed effect, and the counts have no denominator; the scale reflects how widely Linzess is used — Medicare alone paid for it for about 632,000 people in 2024 (CMS). The label's post-marketing section lists hypersensitivity reactions (anaphylaxis, angioedema, rash including hives), blood in the stool, nausea and rectal bleeding.
What is not known
- Duration of episodes. The label states when diarrhoea starts and how often it led to stopping, never how long it lasts.
- Older adults. Of 2,219 IBS-C trial patients, 154 (7%) were 65 or older and 34 (2%) 75 or older; for CIC, 273 of 2,498 (11%) and 56 (2%). The label says this was too few to tell whether older people respond differently.
- Pregnancy. The label says data are insufficient to inform a risk, and that because the drug is not measurably absorbed, maternal use is not expected to expose the fetus. That is a pharmacokinetic statement, not a pregnancy study.
- Beyond 18 months. The long-term data on the label end at 18 months of open-label use.
What Linzess costs, including the 2027 Medicare negotiated price, is on our Linzess cost page. Linzess is one of the peptide drugs on our FDA-approved peptides census; the class-wide picture is on peptide side effects.
Sources
- Linzess (linaclotide) prescribing information, AbbVie, effective 21 May 2026: DailyMed and openFDA label API, read 3 November 2026 (boxed warning; sections 1, 2, 4, 5.1, 5.2, 6.1, 6.2, 8.1, 8.4, 8.5, 12).
- Earlier Linzess label version (2018) via openFDA, boxed warning text, read 3 November 2026.
- Drugs@FDA, NDA 202811 submission history (original approval 30 August 2012; efficacy supplements 25 January 2017, 22 September 2020, 12 June 2023, 4 November 2025, 21 May 2026), via openFDA, data updated 30 October 2026, read 3 November 2026.
- FDA Adverse Event Reporting System via openFDA, query
patient.drug.medicinalproduct:linzess, data updated 28 October 2026, read 3 November 2026. - CMS, Fact Sheet: Negotiated Prices for Initial Price Applicability Year 2027 (enrollees who used Linzess in 2024), read 3 November 2026.