What is Linzess (linaclotide)?

From the Guidelines

Linzess (linaclotide) is recommended for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation in adults, with a strong recommendation and high certainty in the evidence of effects, as stated in the AGA clinical practice guideline 1.

Key Points

• Linzess comes in capsule form with dosages of 72 mcg, 145 mcg, and 290 mcg, typically taken once daily on an empty stomach at least 30 minutes before the first meal of the day.
• For chronic idiopathic constipation, the recommended dose is 145 mcg daily, while for IBS-C, it's 290 mcg daily.
• Linzess works by increasing fluid secretion in the intestines and reducing pain signals from the intestines, helping to relieve constipation and associated abdominal pain.
• Common side effects include diarrhea, abdominal pain, gas, and bloating.
• The medication begins working within the first week for most people, though full benefits may take longer.
• It's essential to note that Linzess should not be used in children under 18 years of age due to risks observed in young laboratory animals, and patients should contact their doctor if they experience severe diarrhea or their symptoms don't improve after taking the medication as prescribed.

Evidence Summary

The AGA clinical practice guideline 1 recommends using linaclotide in patients with IBS-C, with a strong recommendation and high certainty in the evidence of effects. Additionally, the British Society of Gastroenterology guidelines on the management of irritable bowel syndrome 1 support the use of linaclotide as a second-line treatment for IBS-C, with a strong recommendation and high quality of evidence.

From the FDA Drug Label

LINZESS is a prescription medicine used to treat:

• irritable bowel syndrome with constipation (IBS-C) in adults.
• a type of constipation called chronic idiopathic constipation (CIC) in adults.
• functional constipation in children and adolescents 6 to 17 years of age

Linzess Medicine: Linzess (linaclotide) is a guanylate cyclase-C (GC-C) agonist used to treat irritable bowel syndrome with constipation (IBS-C) in adults, chronic idiopathic constipation (CIC) in adults, and functional constipation in children and adolescents 6 to 17 years of age.

• It is available as 72 mcg, 145 mcg, and 290 mcg capsules for oral administration.
• The medication should be taken exactly as prescribed by the doctor, on an empty stomach, at least 30 minutes before a meal, at approximately the same time each day 2.
• Patients who are unable to swallow the capsule whole may open the capsule and administer the contents orally in either applesauce or with bottled water, or administer with water via a nasogastric or gastrostomy tube 2.
• Linzess is not recommended for children less than 2 years of age, as it may cause severe diarrhea and dehydration 2.

From the Research

Linzess Medicine Overview

• Linzess, also known as linaclotide, is a 14-amino acid peptide indicated for the treatment of adults with chronic constipation (CC) and constipation-predominant irritable bowel syndrome (IBS-C) 3.
• It acts on guanylate cyclase-C receptors on the luminal membrane to increase chloride and bicarbonate secretions into the intestine and inhibit the absorption of sodium ions, thus increasing the secretion of water into the lumen and improving defecation 3.

Mechanism of Action and Efficacy

• 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 3.
• In placebo-controlled Phase III clinical trials, linaclotide significantly increased weekly spontaneous bowel movements and complete spontaneous bowel movements (CSBMs) while reducing abdominal pain in patients with CC 3.
• In patients with IBS-C, linaclotide was demonstrated to be effective in meeting FDA-recommended endpoints such as reductions of at least 30% from baseline in abdominal pain scores and CSBM frequency 3.

Adverse Effects and Safety Profile

• The most common adverse effect of linaclotide is diarrhea, which was reported in 16-20% of clinical trial participants 3.
• Linaclotide's adverse effects are generally mild and confined to the gastrointestinal tract 3.
• In clinical studies in Japan, improvements were observed in the responder rates for global assessment of IBS symptom relief, complete spontaneous bowel movements in patients with IBS-C, and the frequency of spontaneous bowel movement in patients with CC, which were maintained during long-term treatment 4.

Comparison with Other Treatments

• A study compared linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa, and found that linaclotide and lubiprostone increase ion transport responses across normal human colon, but linaclotide displays increased sensitivity to the dosing regimen used 5.
• Another study found that lubiprostone is a safe and efficacious drug for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation, with limited adverse effects in 3 months of follow-up 6.