Ibsrela (Tenapanor) for IBS-C: Indication and Dosing
Ibsrela is FDA-approved for the treatment of irritable bowel syndrome with constipation (IBS-C) in adults at a dose of 50 mg orally twice daily, taken immediately before breakfast and dinner. 1
FDA-Approved Indication
- Ibsrela is indicated specifically for treatment of IBS-C in adults only 1
- The drug is contraindicated in patients less than 6 years of age due to risk of serious dehydration observed in nonclinical studies 1
- Safety and effectiveness have not been established in patients less than 18 years of age 1
- Avoid use in patients 6 years to less than 12 years of age 1
Standard Dosing Regimen
The recommended dosage is 50 mg orally twice daily 1
Administration Instructions
- Take immediately prior to breakfast or the first meal of the day 1
- Take the second dose immediately prior to dinner 1
- If a dose is missed, skip the missed dose and take the next dose at the regular time 1
- Do not take 2 doses at the same time 1
Clinical Guideline Support
The American Gastroenterological Association (AGA) suggests using tenapanor in patients with IBS-C (conditional recommendation, moderate certainty of evidence) 2
Efficacy Data
- 34.1% of tenapanor-treated patients met the FDA responder endpoint versus 21.7% with placebo (FDA endpoint = 30% reduction in abdominal pain + 1 additional complete spontaneous bowel movement per week for 6 of 12 weeks) 2
- Tenapanor improved abdominal pain response with a risk difference of 12.1% over placebo 2
- Complete spontaneous bowel movement (CSBM) response improved with a risk difference of 11.3% over placebo 2
- In phase 3 trials, 58.1% of tenapanor patients reported adequate relief of IBS symptoms at 12 weeks versus 41.1% with placebo 2
Contraindications
Absolute contraindications include: 1
- Patients less than 6 years of age
- Known or suspected mechanical gastrointestinal obstruction
Safety Profile and Adverse Effects
Most Common Adverse Reaction
Diarrhea is the most common adverse effect, occurring in approximately 16% of patients versus 4% with placebo 2, 1
- Diarrhea led to treatment discontinuation in 6.6% of tenapanor patients versus 1.0% with placebo 2
- Severe diarrhea occurred in 2.5% of tenapanor-treated patients 1
- Most diarrhea cases were mild to moderate in severity 3
Other Adverse Reactions (≥2%)
- Abdominal distension: 3% versus <1% placebo 1
- Flatulence: 3% versus 1% placebo 1
- Dizziness: 2% versus <1% placebo 1
Management of Severe Diarrhea
If severe diarrhea occurs, suspend dosing and rehydrate the patient 1
Long-Term Safety
- Tenapanor demonstrated similar safety over ≥52 weeks of treatment compared to shorter duration studies 3
- In the open-label extension study (T3MPO-3), diarrhea occurred in 11.1% of patients receiving ≥52 weeks of treatment 3
- No deaths occurred during long-term treatment studies 3
Mechanism of Action
Tenapanor is a first-in-class, minimally absorbed, selective inhibitor of intestinal sodium/hydrogen exchanger isoform 3 (NHE3) 2, 1, 4
- Decreases sodium absorption in the small intestine and colon 2
- Increases water secretion into the intestinal lumen 4
- Has demonstrated antinociceptive (pain-reducing) effects 2, 4
- Plasma concentrations remain well below levels needed for systemic effects, limiting action to the intestinal lumen 5
Drug Interactions
Monitor OATP2B1 substrates (e.g., enalapril) for potential reduced exposure when co-administered with tenapanor 1
- Monitor for signs related to loss of efficacy of the concomitant drug
- Adjust dosage of concomitantly administered drug as needed
Clinical Positioning
The AGA guideline positions tenapanor as a conditional recommendation alongside other secretagogues (plecanatide, linaclotide) for IBS-C, with linaclotide receiving the only strong recommendation 2
Common Pitfall to Avoid
Do not use tenapanor in pediatric patients - the boxed warning emphasizes serious dehydration risk in young patients, and there are no established safety or efficacy data in those under 18 years 1