Digestive & weight Guanylate cyclase-C agonist
Linaclotide
Regulatory status
Status at a glance
503A compounding status
Not nominated
We found no pending nomination for the 503A bulks list. Unless the substance has another legal pathway (for example, a USP monograph or use in an FDA-approved drug), 503A pharmacies generally may not compound with it.
- FDA approval
- An FDA-approved product contains this peptide
- 503B outsourcing
- Not determined
- Anti-doping (WADA)
- Not on the WADA Prohibited List
- DEA schedule
- Not a controlled substance
About peptide status
Most peptides discussed here are not FDA-approved for any use, and products labeled “research use only” are not for human use. Removal from Category 2 does not authorize compounding. PCAC votes are non-binding recommendations; FDA and HHS make the final decisions.
This is not medical or legal advice, and we do not publish dosing, sourcing or reconstitution information. Talk with a licensed clinician before using any peptide.
If you think you are having a medical emergency, call 911.
Key takeaway
Linaclotide (sold as Linzess) is a minimally absorbed peptide that works inside the gut to draw in fluid and ease abdominal pain, used for constipation-predominant irritable bowel syndrome and chronic constipation. It activates a receptor on the intestinal lining that increases fluid secretion and speeds transit. It has been FDA-approved in the U.S. since 2012, is taken as a daily capsule, and carries a boxed warning against use in very young children.
At a glance
- What it is
- A guanylate cyclase-C agonist peptide that acts locally in the gut
- Approved for
- Irritable bowel syndrome with constipation in adults and children 7 and older, chronic idiopathic constipation in adults, and functional constipation in children 2 and older
- Key fact
- In phase 3 trials, about a third of IBS-C patients met the combined responder goal versus roughly 14 percent on placebo
- Route
- Oral (once-daily capsule)
- Evidence strength
- FDA approved
Summary
Linaclotide (Linzess) is an FDA-approved peptide that acts inside the gut to ease IBS-C and chronic constipation. Learn how it works and its risks.
What is linaclotide?
Linaclotide, sold under the brand Linzess (Constella in some regions), is a 14-amino-acid peptide taken by mouth that acts almost entirely within the intestine, since it is barely absorbed into the bloodstream. It is used for chronic constipation and for irritable bowel syndrome with constipation (IBS-C), conditions where slow transit and abdominal discomfort go together. It was developed under the code MD-1100 and approved in the United States in 2012.
How does linaclotide work?
Linaclotide activates guanylate cyclase-C, a receptor on the surface of the cells lining the intestine. Switching on this receptor raises cyclic GMP inside and around those cells, which opens chloride and bicarbonate channels and drives secretion of fluid into the intestinal lumen. The added fluid softens stool and speeds its passage, relieving constipation.
The elevated cyclic GMP outside the cells is also thought to reduce the sensitivity of the pain-sensing nerves in the gut wall, which may explain the reduction in abdominal pain seen in IBS-C. Because linaclotide stays in the gut and is not meaningfully absorbed, its effects are local. In the phase 3 IBS-C program, roughly a third of patients met the FDA combined responder endpoint versus about 14 percent on placebo.
Is it FDA-approved?
Editor’s note
Status: Yes. Linaclotide was approved by the FDA in stages, starting with adults and later extending to children. Indication | Population | FDA approval IBS-C | Adults | 2012 Chronic idiopathic constipation | Adults | 2012 IBS-C | Children 7 and older | Later approval Functional constipation | Children 2 and older | Later approval It carries a boxed warning that it is contraindicated in children under 2 years of age, because in very young animals it caused deaths from severe dehydration.
Category: FDA-approved · Primary body area: Digestive & weight
Yes. Linaclotide was approved by the FDA in stages, starting with adults and later extending to children.
| Indication | Population | FDA approval |
|---|---|---|
| IBS-C | Adults | 2012 |
| Chronic idiopathic constipation | Adults | 2012 |
| IBS-C | Children 7 and older | Later approval |
| Functional constipation | Children 2 and older | Later approval |
It carries a boxed warning that it is contraindicated in children under 2 years of age, because in very young animals it caused deaths from severe dehydration.
What is linaclotide prescribed for?
Linaclotide is prescribed for irritable bowel syndrome with constipation in adults and children 7 and older, chronic idiopathic constipation in adults, and functional constipation in children 2 and older. It is taken once daily on an empty stomach, and it must not be used in children under 2.
What are the side effects?
According to the prescribing information, common side effects include:
- Diarrhea, which is the most common reason for stopping
- Abdominal pain
- Gas and bloating
More serious considerations include:
- Severe diarrhea leading to dehydration
Linaclotide is contraindicated in children under 2 years of age, which is the subject of its boxed warning, and in people with a known or suspected bowel obstruction.
Sources: FDA prescribing information for Linzess; a phase 3 IBS-C trial (Chey et al., American Journal of Gastroenterology, 2012, DOI: 10.1038/ajg.2012.254), indexed on PubMed. This document is educational and does not constitute medical advice.
Registered human trials
4 registered human trials on ClinicalTrials.gov that we reviewed
Sources
- [1]
- [2]
approved (PDF)
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