Linaclotide
Guanylate cyclase-C agonist
Status
Approved
Approved by FDA (Linzess, 2012) for adult IBS with constipation and chronic idiopathic constipation, with the current May 2026 US label also covering IBS-C from age 7 and functional constipation from age 2, and authorised in the EU (Constella, 2012) for adult IBS-C.
Evidence
Strong
Four large phase 3 RCTs (about 600 to 800 patients each) in IBS-C and chronic constipation met their primary endpoints.
Linaclotide is a 14-amino-acid peptide taken as a daily capsule that acts inside the gut to draw fluid into the bowel. It is approved for irritable bowel syndrome with constipation (IBS-C) and chronic constipation.
Structure
14 residuesPoint at a bead, or focus the chain and use the arrow keys, to name it. Pick a chemistry to highlight it.
Sequence as text
H-C-C-E-Y-C-C-N-P-A-C-T-G-C-Y-OH
What it is used for
- IBS with constipation in adults and children 7 years and older (approved)
- Chronic idiopathic constipation in adults (approved)
- Functional constipation in children 2 years and older (approved)
How it works
Linaclotide is structurally related to the gut peptides guanylin and uroguanylin and activates guanylate cyclase-C on the luminal surface of intestinal cells. This raises cyclic GMP, which drives chloride and bicarbonate secretion through the CFTR channel, increasing intestinal fluid and speeding transit. In an animal model of visceral pain it reduced pain-sensing nerve activity through extracellular cyclic GMP. It is barely absorbed and is broken down in the gut to smaller peptides and amino acids.
How strong the evidence is
Strong
Two 12-week phase 3 trials in 1,276 adults with chronic constipation (Lembo 2011, NEJM) met their primary endpoint in 16% to 21% of linaclotide patients versus 3% to 6% on placebo. Two phase 3 trials of about 800 adults each with IBS-C, including a 26-week trial (Chey 2012), showed improvements in abdominal pain and complete bowel movements versus placebo. In adult IBS-C trials diarrhoea affected 20% on linaclotide versus 3% on placebo. Paediatric trials later supported use in IBS-C and functional constipation.
Risks and side effects
- Boxed warning: contraindicated in children under 2 years because of the risk of serious dehydration (deaths occurred in neonatal mice).
- Diarrhoea is the most common side effect (severe in about 2% of adults; 5% stopped treatment for it in IBS-C trials).
- Abdominal pain, flatulence and bloating.
- Contraindicated in known or suspected mechanical bowel obstruction.
Label dosing
Label (adults): 290 mcg orally once daily for IBS-C, or 145 mcg or 72 mcg once daily for chronic idiopathic constipation, on an empty stomach at least 30 minutes before a meal.
Regulatory status
| Region | Year | Approved for |
|---|---|---|
| USFDA | 2012 | IBS with constipation and chronic idiopathic constipation in adults; later extended to paediatric IBS-C (7 years and older) and functional constipation (2 years and older) |
| EUEMA | 2012 | Moderate to severe IBS with constipation in adults |
Status by country
| Jurisdiction | Status | Source |
|---|---|---|
| USUnited States | Authorised medicine | Source 1 |
| EUEuropean Union | Authorised medicine | Source 2 |
| UKUnited Kingdom | Authorised medicine | Source 6 |
| AUAustralia | Authorised medicine | Source 7 |
| CACanada | Authorised medicine | Source 8 |
Trials of Linaclotide to watch
Linaclotide in colorectal neoplasia(opens the source in a new tab)
Linaclotide in Treating Patients With Stages 0-3 Colorectal Cancer
Linaclotide in constipation, ages 2 to 5(opens the source in a new tab)
A Study to Assess Adverse Events and Change in Symptoms With Linaclotide Versus Placebo in Pediatric Subjects, Ages 2 to 5 Years, With Functional Constipation
Timeline
2026
2025
2012
- Approved, US (FDA)IBS with constipation and chronic idiopathic constipation in adults; later extended to paediatric IBS-C (7 years and older) and functional constipation (2 years and older)
- Approved, EU (EMA)Moderate to severe IBS with constipation in adults
Sources
- 01LINZESS (linaclotide) capsules: Prescribing Information(opens the source in a new tab)
- 02Constella: EPAR(opens the source in a new tab)
- 03Two randomized trials of linaclotide for chronic constipation(opens the source in a new tab)
- 04Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety(opens the source in a new tab)
- 05PubChem Compound Summary: Linaclotide (CID 16158208)(opens the source in a new tab)
- 06Constella 290 micrograms hard capsules: Summary of Product Characteristics(opens the source in a new tab)
- 07CONSTELLA linaclotide 145 microgram hard capsule bottle (297703)(opens the source in a new tab)
- 08Drug Product Database: Constella (DIN 02417162)(opens the source in a new tab)
Educational information, not medical advice. Talk to a licensed clinician before starting, stopping or changing any medicine.