Medications for IBS with Constipation (IBS-C)

First-Line Treatment Options

The American Gastroenterological Association suggests polyethylene glycol (PEG) laxatives as a first-line treatment for IBS-C, with low to moderate certainty of evidence 2
PEG works as an osmotic laxative that increases stool frequency, though evidence for improvement in abdominal pain is limited 2
Common side effects of PEG laxatives include bloating, abdominal discomfort, and cramping 3
Soluble fiber such as ispaghula is effective for global symptoms and abdominal pain in IBS-C, and should be started at a low dose (3-4 g/day) and gradually increased to avoid bloating 4

Linaclotide is the most efficacious secretagogue available for IBS-C, though diarrhea is a common side effect, with a strong recommendation and high-quality evidence 1
Lubiprostone, a chloride channel type 2 activator, increases chloride influx into the intestinal lumen, accelerating intestinal transit, and is FDA-approved for women with IBS-C at a dosage of 8 mcg twice daily, with a strong recommendation and moderate-quality evidence 2
Plecanatide, a guanylate cyclase-C agonist, is approved for IBS-C, but has a weak recommendation with very low-quality evidence 1
Tenapanor, a sodium-hydrogen exchange inhibitor, is effective for IBS-C, with a strong recommendation and high-quality evidence 5
Tegaserod, a 5-Hydroxytryptamine 4 receptor agonist, is effective for IBS-C, but is only available in the USA and restricted to women under 65 years without cardiovascular risk factors, with a strong recommendation and moderate-quality evidence 5

Tricyclic antidepressants (TCAs) are effective second-line drugs for global symptoms and abdominal pain, with a strong recommendation and moderate-quality evidence 4
Selective serotonin reuptake inhibitors (SSRIs) may be effective for global symptoms, but have a weak recommendation with low-quality evidence 4

The initial approach to treating IBS-C should include lifestyle modifications and soluble fiber, with consideration of PEG laxatives for constipation symptoms 2, 4
For patients with inadequate response, linaclotide (290 mcg daily) is the most efficacious option for those with predominant constipation, while lubiprostone (8 mcg twice daily) may be considered for those concerned about diarrhea side effects, and TCAs may be added for significant abdominal pain 1, 4
For refractory symptoms, alternative secretagogues (plecanatide, tenapanor) may be considered, as well as tegaserod in women under 65 without cardiovascular risk factors 1, 5, 6

Medication choice should be guided by symptom severity, predominant symptoms, and potential side effect profiles, and patients should be warned about potential side effects, such as diarrhea with linaclotide and tenapanor, and nausea with lubiprostone 1