What is an alternative medication to Ibsrela (tenapanor) for a patient experiencing loose stools?

Alternative to Ibsrela (Tenapanor) for IBS-C Patients with Loose Stools

Lubiprostone is the best alternative to Ibsrela for patients experiencing loose stools, as it is the secretagogue least likely to cause diarrhea among IBS-C medications. 1

Why Lubiprostone is the Optimal Choice

Lubiprostone (8 mcg twice daily) is a chloride channel activator that is significantly less likely to cause diarrhea compared to other secretagogues used for IBS-C. 1 This makes it the ideal replacement when a patient cannot tolerate tenapanor due to loose stools. The British Society of Gastroenterology provides a strong recommendation with moderate-quality evidence for lubiprostone in IBS-C. 1

Key Advantages:

• Lower diarrhea risk: Unlike linaclotide, plecanatide, and tenapanor (which all commonly cause diarrhea), lubiprostone has a more favorable bowel side effect profile 1
• Proven efficacy: Demonstrates improvement in both the FDA composite endpoint (abdominal pain + bowel movements) and abdominal pain alone 1
• FDA-approved: Licensed for IBS-C in women at 8 mcg twice daily 2

Important Caveat:

Nausea is a frequent side effect of lubiprostone that patients must be warned about. 1 This is the trade-off for avoiding diarrhea—patients exchange one side effect for another, though nausea may be more tolerable than persistent loose stools for many patients.

Alternative Options if Lubiprostone is Not Suitable

If Secretagogues Must Be Avoided Entirely:

Consider switching to a different drug class rather than another secretagogue:

• Tricyclic antidepressants (TCAs): Start with amitriptyline 10 mg once daily, titrating to 30-50 mg once daily for global symptoms and abdominal pain 3, 2. TCAs work through gut-brain modulation and do not cause diarrhea. Explain to patients this is for visceral pain modulation, not depression. 3

• Polyethylene glycol (PEG) laxatives: Can be used as first-line therapy for constipation symptoms without the diarrhea risk of secretagogues 2. However, evidence for abdominal pain improvement is limited. 2

If Another Secretagogue Must Be Tried:

Linaclotide (290 mcg once daily) is the most efficacious secretagogue for IBS-C 1, 2, but diarrhea remains a common side effect 1. This would not solve the loose stool problem and is therefore not recommended in this clinical scenario.

Practical Algorithm for Switching

1. Discontinue tenapanor and allow 2-3 days for washout given its minimal systemic absorption 4

2. Start lubiprostone 8 mcg twice daily with food to minimize nausea 2

3. Counsel patient about nausea risk and consider anti-nausea strategies if needed 1

4. If lubiprostone causes intolerable nausea or is ineffective after 4-6 weeks:

   • Switch to a TCA (amitriptyline 10 mg at bedtime, titrate slowly) 3, 2
   • Consider adding PEG laxative for constipation management 2

5. Monitor response at 4-6 weeks and adjust accordingly

Common Pitfalls to Avoid

• Do not switch to linaclotide, plecanatide, or another dose of tenapanor—all secretagogues in this class commonly cause diarrhea 1
• Do not abruptly stop tenapanor and start a TCA simultaneously if the patient is on other serotonergic medications—allow appropriate washout to avoid interactions 3
• Do not forget to warn about nausea with lubiprostone—this is the most common side effect and patients should take it with food 1, 2
• Do not use tegaserod unless the patient is a woman under 65 without cardiovascular risk factors, as it is restricted due to cardiovascular concerns 2