Linaclotide
Also known as: Linzess, Constella
A guanylate cyclase-C agonist peptide for IBS with constipation and chronic constipation. FDA-approved as Linzess since 2012. Prescription medication.
Last updated
Mechanism of Action
Linaclotide is a 14-amino-acid peptide structurally related to guanylin and uroguanylin that binds guanylate cyclase-C on the luminal surface of intestinal epithelium. This raises intracellular and extracellular cyclic GMP, which activates the CFTR channel to secrete chloride and bicarbonate into the lumen, increasing intestinal fluid and speeding transit. Extracellular cGMP is also thought to reduce the firing of colonic pain-sensing nerves. It acts locally and is minimally absorbed.
- Half-life
- Not measurable in plasma at labeled doses (minimal absorption)
- Administration Routes
- Oral
- Research Status
- Clinical
Reported Benefits
- Approved for irritable bowel syndrome with constipation (IBS-C) in adults
- Approved for chronic idiopathic constipation in adults
- Approved for functional constipation in children 6 to 17 years old
- Improves abdominal pain and bowel movement frequency in IBS-C trials
Potential Side Effects
- Diarrhea (most common; severe diarrhea can occur)
- Abdominal pain, flatulence and distension
- Boxed warning: risk of serious dehydration in pediatric patients under 2 years
Common Dosing
Labeled dosing is once daily by mouth on an empty stomach at least 30 minutes before the first meal, with the strength depending on indication and age (adult doses range from 72 mcg to 290 mcg). Dosing is set and supervised by the prescribing clinician.
The dosing information above is aggregated from research literature and anecdotal community reports for educational purposes only. It is not a recommendation, prescription, or medical advice. Peptides are sold as research chemicals only and are not intended for human use.
Contraindications
- Patients under 2 years of age
- Known or suspected mechanical gastrointestinal obstruction
No documented stacking partners for Linaclotide yet.
- View
Two randomized trials of linaclotide for chronic constipation
2011
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Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety
2012
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Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
2024