BETHESDA, MD 31 August 2012—Ironwood Pharmaceuticals Inc. and Forest Laboratories, Inc. on August 30 announced (PDF) the approval of linaclotide oral capsules for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation in adults.
An Ironwood spokeswoman said the company expects to begin selling linaclotide in the United States during the fourth quarter of 2012. The drug will be marketed as Linzess.
According to its FDA-approved labeling (PDF), linaclotide is a guanylate cyclase-C agonist that acts locally in the intestine to reduce intestinal pain and speed gastrointestinal transit.
The recommended dosage of linaclotide for the treatment of IBS-C is 290 µg taken once daily on an empty stomach at least 30 minutes before the first meal of the day. The recommended dosage for the treatment of chronic idiopathic constipation is 145 µg per day.
FDA stated that clinical trial participants with IBS-C who were treated with 290 µg of linaclotide per day reported improvements in abdominal pain and the number of complete spontaneous bowel movements compared with patients who received a placebo.
According to FDA, linaclotide also performed better than placebo at improving bowel function in patients with chronic idiopathic constipation. In this population 145-µg and 290- µg daily doses performed equally well, and the lower dosage is recommended for the treatment of the condition.
A boxed warning in the labeling for linaclotide states that the drug should not be used in pediatric patients and is specifically contraindicated in children up to six years of age.
Linaclotide was found in toxicology studies to cause deaths in neonatal and young juvenile mice but not in older juvenile mice. FDA is requiring the company to conduct additional toxicology studies (PDF) to further characterize these deaths.
In clinical trials involving patients with IBS-C or chronic idiopathic constipation, the most commonly reported adverse events among linaclotide recipients were diarrhea, abdominal pain, flatulence, and abdominal distension.
Linaclotide will be supplied as 145- and 290-µg capsules in bottles of 30 each. The capsules should be protected from moisture and stored at room temperature in the original container, which has a dessicant.