What is the use of Linzess (linaclotide)?

From the Guidelines

Linzess (linaclotide) should be used in patients with irritable bowel syndrome with constipation (IBS-C) as recommended by the American Gastroenterological Association (AGA) with a strong recommendation and high certainty in the evidence of effects. The medication works by increasing intestinal fluid secretion and accelerating bowel movements, and the typical dosage ranges from 72 to 290 mcg taken once daily on an empty stomach, at least 30 minutes before the first meal of the day 1. The 145 mcg dose is commonly prescribed for chronic constipation, while the 290 mcg dose is often used for IBS-C. Some key points to consider when prescribing Linzess include:

• The medication should be swallowed whole, not crushed or chewed
• Common side effects include diarrhea, abdominal pain, and gas
• The medication works by activating guanylate cyclase-C receptors on the intestinal surface, increasing cyclic guanosine monophosphate (cGMP), which increases intestinal fluid and accelerates transit
• Improvement in symptoms typically begins within the first week of treatment
• Linzess is contraindicated in children under 6 years old and in patients with known or suspected mechanical gastrointestinal obstruction 1. The AGA recommends using linaclotide in patients with IBS-C, and this recommendation is based on high-quality evidence from recent studies 1.

From the FDA Drug Label

LINZESS is indicated for the treatment of: • irritable bowel syndrome with constipation (IBS-C) in adults • chronic idiopathic constipation (CIC) in adults • functional constipation (FC) in pediatric patients 6 to 17 years of age The recommended dosages of LINZESS are:

• 290 mcg orally once daily for irritable bowel syndrome with constipation (IBS-C) in adults
• 145 mcg orally once daily for chronic idiopathic constipation (CIC) in adults, with an option to use 72 mcg once daily based on individual presentation or tolerability
• 72 mcg orally once daily for functional constipation (FC) in pediatric patients 6 to 17 years of age 2

From the Research

Linzess Overview

• Linzess, also known as linaclotide, is a medication used to treat irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CC) 3, 4, 5.
• It is a 14-amino acid peptide that acts on guanylate cyclase-C receptors to increase chloride and bicarbonate secretions into the intestine, inhibiting the absorption of sodium ions and increasing water secretion into the lumen 4, 6.

Mechanism of Action

• Linaclotide binds to guanylate cyclase-C receptors on the luminal membrane, resulting in increased intracellular cyclic guanosine monophosphate (cGMP) and subsequent increased fluid secretion and gastrointestinal transit 4, 6.
• This mechanism of action leads to improved defecation and relief of constipation symptoms 4, 5.

Efficacy and Safety

• Clinical trials have demonstrated the efficacy of linaclotide in increasing weekly spontaneous bowel movements and complete spontaneous bowel movements, as well as reducing abdominal pain in patients with IBS-C and CC 4, 7.
• The most common adverse effect of linaclotide is diarrhea, which is generally mild and controllable by decreasing the dose 4, 6.
• Linaclotide has been shown to improve stool form, reduce abdominal pain and bloating, and improve overall symptom severity in patients with IBS-C and CC 7.

Approval and Dosage

• Linaclotide is approved by the Food and Drug Administration (FDA) for oral once-daily administration at doses of 145 μg for CC and 290 μg for IBS-C 4, 5.
• In Japan, linaclotide was approved for IBS-C in 2016 and CC in 2018, with a dosage of 0.25 mg tablets 6.