Linaclotide 290 mcg: A GC-C Agonist for IBS-C Treatment
Linaclotide 290 mcg (Linzess) is a guanylate cyclase-C (GC-C) agonist FDA-approved for treating irritable bowel syndrome with constipation (IBS-C) in adults, working by increasing intestinal fluid secretion and accelerating transit while reducing visceral pain. 1, 2
Mechanism of Action
Linaclotide is a 14-amino acid peptide that:
- Acts locally on the luminal surface of intestinal epithelium
- Binds to GC-C receptors, increasing intracellular and extracellular cyclic guanosine monophosphate (cGMP)
- Stimulates chloride and bicarbonate secretion into the intestinal lumen through CFTR channels
- Increases intestinal fluid and accelerates transit
- Reduces abdominal pain by decreasing visceral hypersensitivity through cGMP elevation 1, 2
Approved Indications and Dosing
The 290 mcg dose is specifically approved for:
- IBS-C in adults (18 years and older)
Other available doses and indications include:
- 145 mcg for chronic idiopathic constipation (CIC) in adults
- 72 mcg for CIC in adults and functional constipation in children 6-17 years 1, 2
Clinical Efficacy
Linaclotide 290 mcg demonstrates significant efficacy for IBS-C:
- 33.7% of patients meet the FDA composite endpoint (improvement ≥30% in abdominal pain plus increase ≥1 complete spontaneous bowel movement) vs 13.9% with placebo (NNT = 5.1) 3
- 48.9% of patients achieve ≥30% reduction in abdominal pain vs 34.5% with placebo 3
- Significantly improves stool consistency, bowel movement frequency, straining, and bloating 3, 4
- Benefits persist throughout 26 weeks of treatment 3
Safety Profile
The most common adverse effect is diarrhea:
- Occurs in approximately 16-20% of patients 1, 5
- Generally mild to moderate in severity
- Led to discontinuation in 4.5% of patients in clinical trials 3
- No serious adverse events of diarrhea were reported 5
Important safety considerations:
- Contraindicated in children under 2 years due to risk of severe dehydration
- Minimal systemic absorption with negligible bioavailability
- Should be taken on an empty stomach, at least 30 minutes before breakfast 1, 2
- Use caution in elderly patients who may be more susceptible to diarrhea-induced dehydration 1, 2
Administration Guidelines
For optimal effectiveness:
- Take once daily on an empty stomach
- Administer at least 30 minutes before the first meal of the day
- Taking with food can result in looser stools and higher stool frequency
- Maintain consistent timing of administration 1, 2
Cost and Access Considerations
- Average cost approximately $523/month
- Insurance coverage varies significantly
- Prior authorization often required
- Patient assistance programs may be available from manufacturers 1
Linaclotide represents an important therapeutic option for IBS-C patients with its dual mechanism addressing both bowel symptoms and abdominal pain, with efficacy demonstrated in multiple large clinical trials.