Ibsrela (tenapanor)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved September 2019

Specific Treatments:

irritable bowel syndrome with constipation in adults

Therapeutic Areas

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General Information

Ibsrela (tenapanor) is a sodium/hydrogen exchanger 3 (NHE3) inhibitor. 

Ibsrela is specifically indicated for the treatment of irritable bowel syndrome with constipation (IBS-C) in adults.

Ibsrela is supplied as a tablet for oral administration. The recommended dosage in adults is 50 mg orally twice daily. Take Ibsrela immediately prior to breakfast or the first meal of the day and immediately prior to dinner. If a dose is missed, skip the missed dose and take the next dose at the regular time. Do not take 2 doses at the same time.

Clinical Results

FDA Approval

The FDA approval of Ibsrela was based on two randomized, double-blind, placebo-controlled trials. The trial designs were identical through the first 12 weeks of treatment, and thereafter differed in that Trial 1 continued for an additional 14 weeks of treatment (26 weeks double-blind treatment), whereas Trial 2 included a 4-week randomized withdrawal (RW) period (12 weeks double-blind treatment). Patients who were enrolled in these trials met the Rome III criteria for IBS-C, related to abdominal pain and bowel movement frequency. The primary endpoint for both trials was the proportion of patients who were responders during the 12-week treatment period. A responder, as defined by the FDA, was a patient who experienced at least a 30% reduction in the weekly average abdominal pain score compared with baseline and an increase of at least 1 complete spontaneous bowel movement (CSBM) in weekly average from baseline, in the same week, for at least 6 of the first 12 treatment weeks. In both trials Ibsrela met the primary endpoint as compared with placebo (Trial 1: 37% versus 24%, Ibsrela versus placebo, respectively. Trial 2: 27% versus 19% Ibsrela versus placebo, respectively). In Trials 1 and 2, the proportion of responders for 9 out of the first 12 weeks, including at least 3 of the last 4 weeks, was greater in Ibsrela-treated patients compared to placebo-treated patients. In addition, in Trial 1, the proportion of responders for 13 out of 26 weeks was greater in Ibsrela‑treated patients compared to placebo-treated patients. In both trials, improvements from baseline in average weekly CSBMs and abdominal pain were observed by Week 1, with improvement maintained through the end of treatment.

Side Effects

Adverse effects associated with the use of Ibsrela may include, but are not limited to, the following:

diarrhea

abdominal distension

flatulence

dizziness

The Ibsrela drug label comes with the following Black Box Warning: Ibsrela is contraindicated in patients less than 6 years of age; in young juvenile rats, tenapanor caused death presumed to be due to dehydration. Avoid use of Ibsrela in patients 6 years to less than 12 years of age. The safety and effectiveness of Ibsrela have not been established in pediatric patients less than 18 years of age. 

Mechanism of Action

Ibsrela (tenapanor) 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. In vitro and animal studies indicate its major metabolite, M1, is not active against NHE3. By inhibiting NHE3 on the apical surface of the enterocytes, tenapanor 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.  Tenapanor has also been shown to reduce abdominal pain by decreasing visceral hypersensitivity and by decreasing intestinal permeability in animal models. In rat model of colonic hypersensitivity, tenapanor reduced visceral hyperalgesia and normalized colonic sensory neuronal excitability.

Additional Information

For additional information regarding Ibsrela or irritable bowel syndrome with constipation in adults, please visit the Ardelyx web page.