Approved & therapeutic
Linaclotide
Linzess
Linaclotide is an orally administered guanylate cyclase-C agonist approved in the US for irritable bowel syndrome with constipation in adults and children seven years and older, chronic idiopathic constipation in adults, and functional constipation in children two years and older. It is minimally absorbed and acts within the gut lumen.
- Status
- Linaclotide is approved by the U.S. FDA and has official prescribing information.
- Evidence
- Approved labeling. Official prescribing information exists, based on clinical trials in people.
- Half-life
- Not established. Systemic availability is negligible and plasma concentrations are below the limit of quantitation at labeled doses, so standard pharmacokinetic parameters including half-life could not be calculated.
- How it's taken
- Oral capsule
- Mechanism
- Other
- Pathways
- Guanylate cyclase-C
How Linaclotide works
Linaclotide is an agonist at guanylate cyclase-C on the luminal surface of intestinal epithelium, raising intracellular and extracellular cyclic GMP. This increases chloride and bicarbonate secretion into the lumen through CFTR, increasing intestinal fluid and accelerating transit. In animal models, extracellular cyclic GMP has been reported to reduce activity of pain-sensing afferent nerves, which is the proposed basis for the abdominal pain effect in IBS with constipation.
What research has looked at
- In the two adult phase 3 IBS-with-constipation trials, the label reports two responder definitions. On the FDA combined responder endpoint (at least a 30 percent reduction in worst abdominal pain plus an increase of at least one complete spontaneous bowel movement, both in the same week, for at least 6 of 12 weeks), roughly 34 percent of treated patients responded versus 21 percent and 14 percent on placebo. On the stricter 9-of-12-week combined responder definition, 12 percent and 13 percent responded versus 5 percent and 3 percent on placebo.
- In the two adult chronic idiopathic constipation trials, the 9-of-12-week complete spontaneous bowel movement responder rate was 20 percent versus 3 percent on placebo in one trial and 15 percent versus 6 percent on placebo in the other.
- Approval for functional constipation in children two years and older was supported by a 12-week double-blind placebo-controlled phase 3 trial in patients aged 2 to 5 years meeting modified Rome IV criteria, which showed significant improvement in spontaneous bowel movement frequency rate versus placebo.
- Systemic absorption is negligible and plasma concentrations are unquantifiable, so the drug acts within the gut lumen rather than systemically. This is a pharmacologic property, not a safety guarantee: the boxed warning hazard in young children is itself a luminal fluid-secretion effect.
Evidence level: Approved labeling. Official prescribing information exists, based on clinical trials in people. These are areas studied or reported, not promised effects.
Reported side effects and risks
- Boxed Warning: contraindicated in patients less than 2 years of age. In nonclinical studies in neonatal mice, a single clinically relevant adult oral dose of linaclotide caused deaths due to dehydration.
- Contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
- Diarrhea is the most common adverse reaction and can be severe; severe diarrhea was reported in about 2 percent of adult IBS-with-constipation and chronic idiopathic constipation patients. The label directs suspending the drug and rehydrating the patient if severe diarrhea occurs. Onset is typically within the first two weeks of treatment.
- Diarrhea was reported in about 20 percent of IBS-with-constipation patients versus 3 percent on placebo, and about 16 percent of chronic idiopathic constipation patients versus 5 percent on placebo. In pediatric functional constipation trials the rate was about 4 percent versus 2 percent on placebo.
- Other common reactions include abdominal pain, flatulence and abdominal distension.
Sources
- PubMed research on Linaclotide · NIH · National Library of Medicine
- DrugBank record for Linaclotide · DrugBank
- Active clinical trials for Linaclotide · U.S. National Library of Medicine
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Linaclotide FAQ
What is Linaclotide?
Linaclotide is an orally administered guanylate cyclase-C agonist approved in the US for irritable bowel syndrome with constipation in adults and children seven years and older, chronic idiopathic constipation in adults, and functional constipation in children two years and older. It is minimally absorbed and acts within the gut lumen.
How does Linaclotide work?
Linaclotide is an agonist at guanylate cyclase-C on the luminal surface of intestinal epithelium, raising intracellular and extracellular cyclic GMP. This increases chloride and bicarbonate secretion into the lumen through CFTR, increasing intestinal fluid and accelerating transit. In animal models, extracellular cyclic GMP has been reported to reduce activity of pain-sensing afferent nerves, which is the proposed basis for the abdominal pain effect in IBS with constipation.
Is Linaclotide FDA approved?
Yes. Linaclotide is approved by the U.S. FDA and has official prescribing information. Evidence level: approved labeling. Official prescribing information exists, based on clinical trials in people.
How is Linaclotide taken?
Oral capsule.
What side effects have been reported with Linaclotide?
Reported in the sources: Boxed Warning: contraindicated in patients less than 2 years of age. In nonclinical studies in neonatal mice, a single clinically relevant adult oral dose of linaclotide caused deaths due to dehydration; Contraindicated in patients with known or suspected mechanical gastrointestinal obstruction; Diarrhea is the most common adverse reaction and can be severe; severe diarrhea was reported in about 2 percent of adult IBS-with-constipation and chronic idiopathic constipation patients. The label directs suspending the drug and rehydrating the patient if severe diarrhea occurs. Onset is typically within the first two weeks of treatment; Diarrhea was reported in about 20 percent of IBS-with-constipation patients versus 3 percent on placebo, and about 16 percent of chronic idiopathic constipation patients versus 5 percent on placebo. In pediatric functional constipation trials the rate was about 4 percent versus 2 percent on placebo; Other common reactions include abdominal pain, flatulence and abdominal distension.
Educational summary compiled from the sources listed above. Not medical advice. Peptide Vault does not sell, source or recommend any compound. Talk to a qualified clinician before starting or changing anything.