Peptide education
Linaclotide
Linzess · MD-1100
Linaclotide is a prescription peptide that acts in the intestine. In the United States, Linzess is approved for certain constipation disorders in adults and children, with different age limits for each condition.
Linzess has placebo-controlled evidence for specific constipation disorders. Diarrhea can be severe, and the medicine must not be used in children under 2 or in people with known or suspected mechanical intestinal obstruction.
Overview
Quick answer
Irritable bowel syndrome with constipation, chronic idiopathic constipation, and pediatric functional constipation are separate label indications. Their approved ages and doses are not the same.
What is linaclotide used for?
The US label covers IBS-C in adults and children aged 7 or older, chronic idiopathic constipation in adults, and functional constipation in children aged 2 or older.
How does it work?
It activates guanylate cyclase-C at the intestinal surface. The resulting signaling increases fluid in the bowel and helps move stool. Blood levels of the drug are generally too low to measure after usual oral doses.
What doses appear on the US label?
For adult IBS-C, the label specifies 290 mcg once daily. For adult chronic idiopathic constipation it specifies 145 mcg, with 72 mcg an option based on presentation or tolerability. Pediatric IBS-C from age 7 is 145 mcg; pediatric functional constipation from age 2 is 72 mcg. These are label descriptions, not individual instructions.
What should a reader know about diarrhea?
Diarrhea is common and can be severe. The label tells patients to stop the medicine and contact their healthcare provider right away for severe diarrhea; it also calls for rehydration when severe diarrhea occurs.
Evidence
Evidence snapshot
In one trial, 33.7% taking 290 mcg and 13.9% taking placebo met a combined pain and bowel-movement response over the first 12 weeks.
A 12-week trial found a bowel-movement response in 13.4% of participants taking 72 mcg and 4.7% taking placebo, using its primary endpoint.
A randomized trial in children aged 6 to 17 found greater improvement in spontaneous bowel-movement frequency with linaclotide. The label also describes a separate trial in children aged 2 to 5.
The boxed warning concerns serious dehydration in children under 2. The label also lists mechanical gastrointestinal obstruction as a contraindication.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Linaclotide can improve IBS-C symptoms. | In a trial of 804 adults, the proportion meeting both pain and stool-frequency criteria was higher with linaclotide than with placebo over 12 weeks. | Intestinal fluid secretion is a recognized effect of GC-C activation. A proposed effect on pain-sensing nerves comes from an animal model. | Supported for the studied adult IBS-C population, although most participants did not meet the combined response definition. |
| Linaclotide is approved for every child with constipation. | The label includes functional constipation from age 2 and IBS-C from age 7. It contraindicates use below age 2 and does not establish IBS-C safety or effectiveness below age 7. | No. Age, diagnosis, and the label's other contraindications matter. | |
| An oral drug with low absorption cannot cause serious effects. | Diarrhea is the most common adverse reaction and can be severe. Postmarketing reports include severe diarrhea with dehydration-related complications. | Incorrect. Local intestinal activity can still cause clinically important fluid loss. |
Bottom line
Main takeaway
Linzess is a prescription capsule for particular constipation conditions. Improvement is not guaranteed, and severe diarrhea needs prompt attention.
Look at the condition, age, administration instructions, and side effects for each product. The label has distinct pediatric age limits for functional constipation and IBS-C.
The adult IBS-C composite requires improvement in both pain and bowel movements during the same weeks. The adult constipation trial's primary endpoint required a bowel-movement response in at least 9 of 12 weeks.
Identity
What it is
Linaclotide is a 14-amino-acid peptide related in structure to the gut signaling peptides guanylin and uroguanylin. Linzess is supplied in 72 mcg, 145 mcg, and 290 mcg capsules.
Chronic idiopathic constipation describes persistent constipation without an identified cause. IBS-C is a distinct diagnosis that includes abdominal symptoms as well as constipation.
Use context
Routes, doses, and cycle patterns
Linzess is taken on an empty stomach at least 30 minutes before a meal. The labeled dose depends on the condition and the patient's age.
Human studies and product labels
Adult IBS-C label
- Context
- US prescribing information
- Route
- Oral capsule
- Amount
- 290 mcg
- Frequency
- Once daily
The label provides separate instructions for patients unable to swallow the capsule whole.
Adult chronic idiopathic constipation label
- Context
- US prescribing information
- Route
- Oral capsule
- Amount
- 145 mcg; 72 mcg may be used based on presentation or tolerability
- Frequency
- Once daily
The dose described for IBS-C should not be substituted for this indication without clinical direction.
Pediatric IBS-C label
- Context
- Patients aged 7 and older
- Route
- Oral capsule
- Amount
- 145 mcg
- Frequency
- Once daily
Safety and effectiveness for pediatric IBS-C below age 7 have not been established.
Pediatric functional constipation label
- Context
- Patients aged 2 and older
- Route
- Oral capsule
- Amount
- 72 mcg
- Frequency
- Once daily
Use below age 2 is contraindicated because of the risk of serious dehydration.
Adult IBS-C study
- Context
- Randomized, placebo-controlled trial
- Route
- Oral
- Amount
- 290 mcg
- Frequency
- Once daily
- Duration
- 26 weeks; primary response assessed over the first 12 weeks
This is the trial regimen, not a recommended course for an individual.
What varies
- Diagnosis and age determine which labeled indication and dose apply.
- The label describes how to handle missed doses and administration difficulties; consult the full instructions.
- Severe diarrhea, suspected obstruction, and accidental ingestion by a young child need prompt clinical attention.
Research
Research evidence
Randomized adult trials studied IBS-C and chronic idiopathic constipation using different response definitions. A separate trial studied functional constipation in children aged 6 to 17. The prescribing information also describes pediatric IBS-C and functional constipation trials in younger children, so age-specific claims should remain attached to the relevant study.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Adult IBS-C phase 3 trial | 804 adults with IBS-C | Randomized, double-blind trial of 290 mcg daily versus placebo for 26 weeks | Oral linaclotide in a controlled study | The combined endpoint was met by 33.7% of the linaclotide group and 13.9% of the placebo group over the first 12 weeks. Response required at least 30% less abdominal pain and at least one additional complete spontaneous bowel movement per week, in the same week, for at least 6 of 12 weeks. | This is a defined composite rather than complete symptom resolution. Diarrhea caused discontinuation in 4.5% of treated participants and 0.2% of placebo participants. | Strong human evidence for studied adult IBS-C |
| Adult chronic idiopathic constipation trial | 1,223 adults with chronic idiopathic constipation | Randomized, double-blind, placebo-controlled trial over 12 weeks | Oral linaclotide 72 mcg or 145 mcg daily | The primary response was met by 13.4% of the 72 mcg group versus 4.7% of placebo. It required at least three complete spontaneous bowel movements per week and an increase of at least one from baseline in the same week, for at least 9 of 12 weeks. | The endpoint does not capture every possible symptom improvement. The trial assessed treatment for 12 weeks. | Strong human evidence for studied adult constipation |
| Pediatric functional constipation phase 3 trial | 328 treated patients aged 6 to 17 | Randomized, double-blind, placebo-controlled trial over 12 weeks | Oral linaclotide 72 mcg daily | The increase in spontaneous bowel movements per week was greater with linaclotide than placebo. Diarrhea was reported in 4% and 2%, respectively. | One treated participant had severe diarrhea with dehydration requiring hospitalization. This trial did not include patients younger than 6. | Strong human evidence for the studied pediatric group |
| Pediatric label clinical studies | Patients aged 2 to 5 with functional constipation and aged 7 to 17 with IBS-C | Separate 12-week studies described in US prescribing information | Approved oral capsule | The label reports improved bowel-movement frequency versus placebo in the younger functional constipation study and describes a pediatric IBS-C study. | The pediatric IBS-C study compared two linaclotide doses without a placebo group; the label also relies on evidence from adult studies for that indication. | Label-supported, with study designs kept distinct |
Cautions
Safety and unknowns
- Linzess is contraindicated in children under 2. The boxed warning reflects deaths from dehydration in neonatal mice after a single dose, not a trial showing those deaths in children.
- It is also contraindicated when mechanical gastrointestinal obstruction is known or suspected. A new or severe abdominal symptom deserves clinical assessment rather than an assumption that it is ordinary constipation.
- The label advises stopping Linzess and contacting a healthcare provider promptly for severe diarrhea. It calls for rehydration if severe diarrhea occurs. Unusual or severe abdominal pain, especially with bloody or black stools, requires urgent medical attention.
- Pregnancy data are insufficient to establish a drug-associated risk. Low systemic absorption does not replace an individual pregnancy or breastfeeding discussion with a healthcare provider.
Mechanism
How it is proposed to work
Linaclotide activates a receptor on the intestinal lining. The resulting fluid secretion helps stool pass through the bowel.
GC-C activation raises cyclic GMP. Within intestinal cells, that signal promotes chloride and bicarbonate secretion through CFTR, increasing intestinal fluid and transit.
The label describes reduced activity of pain-sensing nerves in an animal model. That mechanism is not direct proof of pain relief in a particular person; adult IBS-C trials measured pain outcomes separately.
Details
Technical details
Sources
References
- 1.
FDA. Linzess prescribing information
US indications, age limits, dosing, contraindications, safety, and clinical studies.
- 2.
PubMed. Linaclotide for irritable bowel syndrome with constipation: a 26-week randomized trial
doi:10.1038/ajg.2012.254 PMID:22986437
Placebo-controlled adult IBS-C trial; the combined responder endpoint was evaluated over 12 weeks.
- 3.
PubMed. Low-dose linaclotide for chronic idiopathic constipation: a randomized trial
doi:10.1038/ajg.2017.230 PMID:29091082
Placebo-controlled adult chronic idiopathic constipation trial of 72 mcg and 145 mcg.
- 4.
PubMed. Linaclotide for functional constipation in pediatric patients: a phase 3 trial
doi:10.1016/S2468-1253(23)00398-9 PMID:38211604 NCT04026113
Placebo-controlled functional constipation trial in patients aged 6 to 17 years.