What medications can be given to a patient with Irritable Bowel Syndrome with Constipation (IBSC)?

Pharmacological Management of IBS-C

Linaclotide is the first-line pharmacological agent for IBS-C, with a strong recommendation based on high-quality evidence showing improvement in both abdominal pain and bowel movements. 1

First-Line Pharmacological Therapy

Linaclotide (Strongest Recommendation)

• Start with 290 mcg once daily orally for patients with IBS-C who have failed conservative measures 1
• This guanylate cyclase-C agonist provides modest but clinically meaningful improvement in the FDA composite endpoint (combined improvement in abdominal pain AND increase of ≥1 complete spontaneous bowel movements per week) 1
• Also improves global IBS symptoms and reduces abdominal bloating 1
• Main limitation: diarrhea occurs in a small percentage of patients, leading to treatment discontinuation 1
• Higher out-of-pocket costs may be a barrier for some patients 1

Lubiprostone (Alternative First-Line Option)

• Dose: 8 mcg twice daily with food and water for women with IBS-C 1, 2
• This chloride channel-2 activator has a conditional (weaker) recommendation based on moderate-quality evidence 1
• Shows small improvement in global IBS symptoms and abdominal pain, but did NOT meet statistical significance for adequate spontaneous bowel movement response in the pivotal trials 1
• Nausea is the most common adverse effect (8% of patients), though typically mild 2
• Take with food to reduce nausea 2
• Swallow capsules whole; do not break apart or chew 2
• Few other adverse effects and generally well tolerated long-term 1, 2

Second-Line Options

Polyethylene Glycol (PEG)

• Conditional recommendation with low-quality evidence specifically for IBS-C 1
• Start with 17 g daily and titrate based on symptom response 1
• While effective for chronic constipation, the single IBS-C trial showed improvement in stool frequency but NOT in the composite FDA endpoint (pain + bowel movements) or abdominal pain alone 1
• Consider as a cost-effective option when prescription agents are not accessible, but recognize limited evidence for IBS-specific symptom improvement 1

Plecanatide

• Another guanylate cyclase-C agonist similar to linaclotide 1
• Dose: 3 mg once daily 1
• Also approved for IBS-C treatment 1
• Diarrhea may occur in a subset of patients leading to discontinuation 1

Important Clinical Considerations

Dosing Adjustments for Lubiprostone

• Moderate hepatic impairment (Child-Pugh Class B): No adjustment needed for IBS-C dose 2
• Severe hepatic impairment (Child-Pugh Class C): Reduce to 8 mcg once daily 2

Common Pitfalls to Avoid

• Do not use lubiprostone in patients with known or suspected mechanical gastrointestinal obstruction 2
• Avoid lubiprostone in patients with severe diarrhea 2
• Be aware that syncope and hypotension have been reported postmarketing, particularly with the 24 mcg dose used for chronic constipation; most cases occurred within an hour of the first or subsequent doses 2
• Patients should discontinue lubiprostone and contact their provider if severe diarrhea occurs 2

Treatment Algorithm

1. Start with linaclotide 290 mcg once daily as first-line pharmacological therapy based on the strongest evidence 1
2. If cost is prohibitive or patient experiences intolerable diarrhea, switch to lubiprostone 8 mcg twice daily with food 1
3. If prescription agents are not accessible, consider PEG 17 g daily, recognizing its limited evidence for IBS-specific symptom improvement 1
4. Periodically reassess the need for continued therapy 2

Duration of Benefit

• Lubiprostone's beneficial effects on IBS-C symptoms have been shown to continue for up to 4 weeks after cessation of treatment 3
• Long-term safety has been demonstrated for up to 36 weeks in open-label extension studies 4