The Food and Drug Administration has approved revised prescribing information for Linzess (linaclotide) updating the contraindications and warnings related to children.

Linzess, a guanylate cyclase-C (GC-C) agonist, is indicated in adults for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. The updated label now states that the treatment is contraindicated in patients less than 2 years of age due to the risk of serious dehydration.

Previously, the use of Linzess was contraindicated in children less than 6 years old. Additionally, treatment was to be avoided in those 6 years to less than 18 years old; this statement has since been removed from the Boxed Warning.

The labeling modification is based on data from a human GC-C ontogeny study, which measured GC-C mRNA expression levels in duodenal and colonic mucosal tissue samples from children aged 6 months to less than 18 years (N=99). The study was conducted to evaluate the risk of diarrhea and severe dehydration due to GC-C agonism in children.

Findings showed that in children 2 to less than 18 years, there was no age-dependent trend in GC-C intestinal expression. However, in children under 2 years, data were insufficient to assess the risk and its possible consequences. In neonatal mice, linaclotide has caused deaths due to severe dehydration.

“The warning on the Linzess label at launch was primarily applied due to preclinical findings, and there was an absence of any clinical data in pediatric populations at the time,” said Michael Shetzline, MD, PhD, chief medical officer, senior vice president and head of drug development at Ironwood. “Since approval, we have worked diligently on generating clinical data to better characterize the safety profile for pediatric populations.”

According to Ironwood, the labeling modifications were also based on clinical study data in children with functional constipation, postmarketing data in children who took Linzess, data from the IBM® MarketScan® database, as well as a retrospective review of children who had taken Linzess at the Nationwide Children’s Hospital in Columbus, Ohio.

Further clinical data are needed to establish the safety and effectiveness of Linzess in patients less than 18 years of age.  


  1. Ironwood Pharmaceuticals announces FDA approval of revised Linzess® (linaclotide) label. News release. August 26, 2021.
  2. Linzess [package insert]. Boston, MA: Ironwood Pharmaceuticals, Inc. 2021.