Linaclotide

Guanylate cyclase-C agonist, IBS-C treatment

Linaclotide

Linzess

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Summary

Classes

Guanylate cyclase-C agonist, IBS-C treatment

Common uses

IBS with predominant constipation0, Chronic idiopathic constipation0, Functional constipation in pediatric patients 6-17 years0

Pharmacy

Starting dose

145 mcg PO once daily for chronic idiopathic constipation; 290 mcg daily for IBS-C; pediatric 72 mcg daily

Preparations

72, 145, 290 mcg capsules

US FDA Max

290 mcg/d

Pharmacology

Routes

Oral

Onset

Bowel movement within 1 week; abdominal pain improvement over weeks

Duration

24 hours

Half-life

Not meaningfully described (negligible systemic absorption — the drug acts locally and is degraded in the GI tract)^[1]

Bioavailability

Negligible systemic absorption^[1]

Pregnancy

Limited data; minimal systemic absorption likely renders fetal risk low.^{[citation needed]}

Legal status

Rx-only in US. Carries a Boxed Warning contraindicating use in children <2 years (lethal dehydration in animal studies)^[1]

Purported mechanism

Linaclotide is a 14-amino-acid peptide agonist of guanylate cyclase-C (GC-C) on the luminal surface of intestinal epithelial cells; receptor activation raises intracellular and extracellular cGMP, which opens the CFTR chloride channel and increases chloride/bicarbonate secretion (and consequently water) into the gut lumen, accelerating transit.0 Extracellular cGMP separately activates submucosal sensory afferents in a way that reduces visceral pain perception, distinguishing linaclotide from purely osmotic laxatives in IBS-C. Diarrhea is the dose-limiting effect^[1].

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 FDA Prescribing Information, Linzess (linaclotide), AbbVie/Ironwood, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202811s011lbl.pdf

[linzess-label-1] 1.0 ^1.1 ^1.2 ^1.3 FDA Prescribing Information, Linzess (linaclotide), AbbVie/Ironwood, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202811s011lbl.pdf

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