What is the maximum recommended dose of Ibsrela (tenapanor) for irritable bowel syndrome with constipation?

Maximum Dose of Ibsrela (Tenapanor) for IBS-C

The maximum recommended dose of Ibsrela (tenapanor) for irritable bowel syndrome with constipation (IBS-C) is 50 mg twice daily. 1

Dosing Information

Ibsrela (tenapanor) is a sodium-hydrogen exchange inhibitor that is FDA-approved for the treatment of IBS-C in adults. The dosing regimen is straightforward:

• Standard dose: 50 mg twice daily
• Administration: Take immediately prior to breakfast and immediately prior to dinner
• Maximum dose: 50 mg twice daily (100 mg total daily dose)
• Missed dose handling: If a dose is missed, skip it and take the next dose at the regular time; do not double up doses 1

Mechanism of Action and Efficacy

Tenapanor works as a sodium-hydrogen exchange inhibitor, specifically targeting NHE3 (sodium/hydrogen exchanger isoform 3) in the intestine. This mechanism:

• Reduces sodium absorption in the intestine
• Increases intestinal fluid volume
• Accelerates transit time
• Softens stool consistency

The British Society of Gastroenterology guidelines recognize tenapanor as an efficacious second-line drug for IBS-C in secondary care, with high-quality evidence supporting its use 2. Clinical trials have demonstrated that tenapanor is effective for treating global symptoms of IBS-C, though diarrhea is a common side effect.

Safety Considerations

When prescribing Ibsrela at its maximum dose, be aware of these important safety considerations:

• Contraindications:

  • Patients less than 6 years of age (risk of serious dehydration)
  • Patients with known or suspected mechanical gastrointestinal obstruction 1

• Warnings:

  • Avoid use in patients 6 years to less than 12 years of age
  • Not established for safety and effectiveness in patients under 18 years
  • Diarrhea is the most common adverse reaction (16% vs 4% with placebo) 1
  • Severe diarrhea reported in 2.5% of treated patients 1

Management of Adverse Effects

If severe diarrhea occurs while on the maximum dose:

1. Suspend dosing
2. Rehydrate the patient
3. Consider restarting at the same dose once symptoms resolve, as long-term studies show continued tolerability 3

Long-term Safety

The T3MPO-3 extension study demonstrated that tenapanor remains tolerable over ≥52 weeks of treatment at the standard dose of 50 mg twice daily, with a safety profile similar to shorter studies 3. This supports the continued use of the maximum recommended dose for long-term management of IBS-C when appropriate.

Clinical Context

Tenapanor is positioned as a second-line treatment for IBS-C after failure of first-line therapies such as fiber supplementation and osmotic laxatives. The maximum dose should not be exceeded as there is no evidence supporting higher doses for improved efficacy, and doing so may increase the risk of adverse effects, particularly diarrhea.