Medications for IBS with Constipation (IBS-C)

Linaclotide is the most efficacious first-line secretagogue for IBS-C, though diarrhea is a common side effect. 1

First-Line Treatment Options

Polyethylene glycol (PEG) laxatives are suggested as a first-line treatment for IBS-C, with low to moderate certainty of evidence 1
PEG works as an osmotic laxative that increases stool frequency, though evidence for improvement in abdominal pain is limited 1
Common side effects include bloating, abdominal discomfort, and cramping 1

Soluble fiber such as ispaghula is effective for global symptoms and abdominal pain in IBS-C 1
Should be started at a low dose (3-4 g/day) and gradually increased to avoid bloating 1
Insoluble fiber (e.g., wheat bran) should be avoided as it may worsen symptoms 1

Guanylate cyclase-C agonist that is FDA-approved for IBS-C in adults 2
Recommended dose for IBS-C: 290 mcg orally once daily on an empty stomach, at least 30 minutes before a meal 2
Strong recommendation with high-quality evidence 1
Most efficacious secretagogue available for IBS-C, though diarrhea is a common side effect 1
Take on an empty stomach at approximately the same time each day 2

Chloride channel type 2 activator that increases chloride influx into the intestinal lumen, accelerating intestinal transit 1
FDA-approved for women with IBS-C at a dosage of 8 mcg twice daily 1, 3
Strong recommendation with moderate-quality evidence 1
Less likely to cause diarrhea than other secretagogues, but nausea is a frequent side effect 1
Shown to be well-tolerated for up to 13 months of treatment 1, 4

5-Hydroxytryptamine 4 receptor agonist effective for IBS-C 1
Strong recommendation with moderate-quality evidence 1
Only available in the USA and restricted to women under 65 years without cardiovascular risk factors 1
Diarrhea is a common side effect 1

Tricyclic antidepressants (TCAs) are effective second-line drugs for global symptoms and abdominal pain 1
Start at a low dose (e.g., amitriptyline 10 mg once daily) and titrate slowly to 30-50 mg once daily 1
Strong recommendation with moderate-quality evidence 1
Selective serotonin reuptake inhibitors (SSRIs) may be effective for global symptoms 1
Weak recommendation with low-quality evidence 1

Initial approach:
- Start with lifestyle modifications and soluble fiber 1
- Consider PEG laxatives for constipation symptoms 1
If inadequate response:
- For patients with predominant constipation: Linaclotide (290 mcg daily) is the most efficacious option 1
- For patients concerned about diarrhea side effects: Consider lubiprostone (8 mcg twice daily) 1
- For patients with significant abdominal pain: Consider adding a TCA 1
For refractory symptoms:
- Consider alternative secretagogues (plecanatide, tenapanor) 1
- In women under 65 without cardiovascular risk: Consider tegaserod 1

Medication choice should be guided by symptom severity, predominant symptoms, and potential side effect profiles 5, 6
Secretagogues (linaclotide, lubiprostone) have different mechanisms of action and side effect profiles, allowing for tailored therapy 7, 8
Patients should be warned about potential side effects - diarrhea with linaclotide and tenapanor; nausea with lubiprostone 1
Most medications for IBS-C improve both bowel habits and abdominal pain, though to varying degrees 7
Long-term safety has been established for lubiprostone (up to 13 months) 4 and should be considered for chronic therapy