FDA Drug Alert Warns That Linzess Should Not Be Used In Children Under Age 6 And Neither Safety Nor Efficacy Established For Those Under 18 Years Old
UPDATE: "Synergy Petitions FDA to Update Linzess Labeling" (FDA News, 3/2/18)
In a citizen’s petition to the FDA, Synergy Pharmaceuticals urged the FDA to require a revision of the approved package insert of Ironwood Pharmaceutical’s irritable bowel syndrome medication Linzess (linaclotide).
Synergy claimed the Linzess package insert fails to provide adequate information for its use because the incidences of adverse effects in its clinical trials are unclear or misrepresented....
Linzess (linaclotide) was approved by the FDA in 2012 for irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation. It is from Forest Pharmaceuticals, Inc., who has advertisements for this relatively new drug on television and in magazines.
As announced by the FDA by means of an August 15, 2014 MedWatch Safety Information email alert, in July 2014 there were several major label changes made to the following sections of the Linzess Prescribing Information (accessed 8/18/14):
-- Boxed Warning;
-- Contraindications (4);
-- Warnings and Precautions, Pediatric Risk (5.1); and,
-- Warnings and Precautions, Diarrhea.
The new Linzess "Black-Box" Warning states:
WARNING: PEDIATRIC RISK
- LINZESS is contraindicated … in nonclinical studies, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration in young juvenile mice. …The safety and efficacy of LINZESS has not been established in pediatric patients under 18 years of age
Strictly Confidential, No Obligation
And here is another one of the rather alarming label changes for Linzess made by the FDA and Forest Pharmaceuticals in July 2014:
WARNINGS AND PRECAUTIONS
- LINZESS is contraindicated in children under 6 years of age. The safety and effectiveness of LINZESS in pediatric patients under 18 years of age have not been established. In neonatal mice, increased fluid secretion as a consequence of GC-C agonism resulted in mortality within the first 24 hours due to dehydration. Due to increased intestinal expression of GC-C, children under 6 years of age may be more likely than older children and adults to develop significant diarrhea and its potentially serious consequences…
The bottom line is that starting last month Linzess should not be prescribed to children less than 6 years old because it may harm them.
And as for older children up to age 18, it appears there is no certainty that Linzess is either a safe drug or an effective drug.
There is no indication that Forest has sent a so-called "Dear Doctor" letter to health care providers about these several important major label changes to the effect that Linzess is not a safe IBS and chronic constipation drug for young children.
One wonders whether this July 2014 FDA / Forest Linzess label change might have come too late for some pediatric patients who used Linzess and then suffered "significant diarrhea and its potentially serious consequences".