What is IBSRELA (Irritable Bowel Syndrome with Constipation medication, tenapanor)?

What is IBSRELA?

IBSRELA (tenapanor) is an FDA-approved prescription medication for treating irritable bowel syndrome with constipation (IBS-C) in adults, dosed at 50 mg twice daily immediately before breakfast and dinner. 1

Mechanism of Action

Tenapanor is a first-in-class, small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger isoform 3 (NHE3), which is expressed on the apical surface of the small intestine and colon. 2

The drug works through multiple mechanisms:

• Decreases sodium and phosphate absorption in the intestinal lumen 2
• Increases water secretion into the gut to maintain osmotic balance 2, 3
• Has antinociceptive effects that directly reduce abdominal pain 2, 4
• Is locally acting and minimally absorbed systemically, which reduces drug-drug interactions and systemic toxicity 2, 5

Clinical Efficacy

The American Gastroenterological Association (AGA) conditionally recommends tenapanor for IBS-C patients based on moderate-certainty evidence. 2

Key efficacy outcomes from three randomized controlled trials:

• 34.1% of tenapanor patients met the FDA composite endpoint (improvement in both abdominal pain and bowel movements) versus 21.7% with placebo 2
• 58.1% reported adequate relief of IBS symptoms at 12 weeks versus 41.1% with placebo 2
• Improved abdominal pain with a 12.1% absolute risk difference (RR 0.81; 95% CI 0.73-0.88) 2
• Improved complete spontaneous bowel movements with an 11.3% absolute risk difference (RR 0.83; 95% CI 0.77-0.90) 2

Notably, tenapanor improves abdominal symptoms independent of its effect on bowel movements, making it effective even in patients who don't experience increased bowel frequency. 6

Dosing and Administration

The FDA-approved regimen is 50 mg twice daily:

• Take immediately before breakfast (or first meal of the day) 4, 1
• Take immediately before dinner 4, 1
• If a dose is missed, skip it and take the next dose at the regular time—do not double dose 1

Twice-daily dosing produces superior pharmacodynamic effects compared to once-daily dosing with equivalent total daily doses. 4

Safety Profile

Diarrhea is the most common adverse event, occurring in 14.8% of tenapanor patients versus 2.3% with placebo. 2

Important safety considerations:

• Diarrhea led to discontinuation in only 6.6% of patients versus 1.0% with placebo 2
• Most diarrhea cases are mild to moderate in severity 7
• Other common side effects include abdominal distension, flatulence, and dizziness 1
• No deaths occurred in clinical trials 2
• Long-term safety data up to 52 weeks shows similar tolerability to shorter studies 7

Critical contraindications and warnings:

• Contraindicated in children under 6 years of age due to risk of severe diarrhea and dehydration 1
• Not recommended for children 6 to <18 years 1
• Contraindicated in patients with bowel obstruction 1
• Patients should stop tenapanor and contact their provider if severe diarrhea develops 1

Storage and Handling

Store at room temperature (68°F to 77°F) in the original container to protect from moisture. 1

• Keep the desiccant canister in the bottle—do not remove it 1
• Do not repackage or subdivide the medication 1
• Keep tightly closed in a dry place 1

Alternative Options for Patients with Diarrhea

If a patient develops loose stools or diarrhea on tenapanor, lubiprostone (8 mcg twice daily) is the preferred alternative as it has a significantly lower risk of diarrhea compared to other secretagogues. 8

When switching from tenapanor to lubiprostone:

• Discontinue tenapanor and allow 2-3 days for washout 8
• Start lubiprostone 8 mcg twice daily with food to minimize nausea 8
• Warn patients about nausea, which is a frequent side effect of lubiprostone that can be mitigated by taking with food 8