The Food and Drug Administration (FDA) has approved Ibsrela (tenapanor; Ardelyx) for the treatment of irritable bowel syndrome with constipation (IBS-C) in adults.
Ibsrela is a locally-acting inhibitor of the sodium/hydrogen exchanger 3 (NHE3), an antiporter expressed on the apical surface of the small intestine and colon primarily responsible for the absorption of dietary sodium. By inhibiting NHE3, Ibsrela reduces absorption of sodium from the small intestine and colon, resulting in an increase in water secretion into the intestinal lumen, which accelerates intestinal transit time and results in a softer stool consistency.
The approval was based on 2 placebo-controlled trials in which patients with IBS-C were administered Ibsrela immediately prior to the first meal of the day and immediately before dinner. The trial designs were similar through the first 12 weeks of treatment, and thereafter differed in that Trial 1 continued for an additional 14 weeks of treatment, whereas Trial 2 included a 4-week randomized withdrawal period.
The primary end point in both studies was the proportion of responders, defined as a patient achieving both the stool frequency (CSBM; patient who experienced an increase of at least 1 CSBM in weekly average from baseline) and abdominal pain intensity (patient who experienced at least a 30% reduction in the weekly average of abdominal pain score compared with baseline) responder criteria in the same week for at least 6 of the first 12 weeks of treatment.
Results showed that in both trials, the proportion of responders was greater in the Ibsrela group compared with placebo (Trial 1: 37% vs 24%; treatment difference: 13%; Trial 2: 27% vs 19%; treatment difference: 8%). In addition, improvements from baseline in average weekly CSBMs and abdominal pain were observed by Week 1, with improvement maintained through the end of treatment in both trials.
With regard to safety, the most common adverse reactions were diarrhea, abdominal distension, flatulence, and dizziness. The prescribing information for Ibsrela includes a Boxed Warning regarding the risk of serious dehydration in pediatric patients; Ibsrela is contraindicated for use in patients <6 years old and should be avoided in patients 6 to 12 years of age. The safety and effectiveness of Ibsrela have not been established in patients <18 years of age.
Ibsrela will be supplied as 50mg tablets in 60-count bottles.
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