Linaclotide Dosing and Administration
For IBS-C, use linaclotide 290 mcg once daily; for chronic idiopathic constipation, use 145 mcg once daily (with 72 mcg as an alternative based on tolerability). 1
Dosing by Indication
Irritable Bowel Syndrome with Constipation (IBS-C)
- 290 mcg orally once daily is the FDA-approved dose for adults with IBS-C 1
- This dose has been extensively validated in multiple Phase 3 trials, achieving FDA composite endpoint responder rates of 33.6-33.7% versus 13.9-21.0% for placebo 2
- The composite endpoint requires both ≥30% reduction in worst abdominal pain AND ≥1 complete spontaneous bowel movement (CSBM) increase per week for at least 6 of 12 weeks 2
Chronic Idiopathic Constipation (CIC)
- 145 mcg once daily is the standard recommended dose for adults with CIC 1
- 72 mcg once daily may be used as an alternative based on individual presentation or tolerability concerns 1
- The American Gastroenterological Association strongly recommends linaclotide as second-line therapy for CIC patients who fail over-the-counter laxatives 3
Pediatric Functional Constipation (Ages 6-17)
- 72 mcg once daily for pediatric patients aged 6 to 17 years with functional constipation 1
Critical Administration Instructions
Timing and Food Interactions
- Take on an empty stomach at least 30 minutes before the first meal of the day 1, 4
- Taking with food significantly reduces efficacy 4
- Administer at approximately the same time each day 1
Missed Dose Protocol
- If a dose is missed, skip it and take the next dose at the regular scheduled time 1, 4
- Never take 2 doses at the same time to minimize risk of adverse effects 4
Capsule Administration
- Swallow capsules whole—do not crush or chew 1
- For patients unable to swallow capsules, open and mix with applesauce or water, or administer via nasogastric/gastrostomy tube 1
- When mixing with water: use 30 mL room-temperature bottled water, swirl for 20 seconds, consume immediately 1
- The beads will remain visible and will not dissolve; the drug coating dissolves off the beads 1
Safety Considerations
Contraindications
- Absolutely contraindicated in patients under 2 years of age due to risk of fatal dehydration 1
- Contraindicated in known or suspected mechanical gastrointestinal obstruction 3, 4
Common Adverse Effects
- Diarrhea is the most common adverse event, occurring in 16-20% of patients versus 2-3% with placebo 5, 6
- Approximately 90.5% of diarrhea cases are mild to moderate 5
- Discontinuation due to diarrhea occurs in 4.0-4.5% of linaclotide patients versus 0.2-0.3% of placebo patients 5, 7
- Diarrhea incidence: 1.1 events per patient-year in controlled trials, decreasing to 0.3 in long-term studies 5
Long-Term Safety
- Treatment duration in clinical trials was typically 12-26 weeks, though the FDA label does not limit treatment duration 3
- Long-term safety data up to 104 weeks confirms overall safety profile 5
- Most common reasons for discontinuation over the first year are loss of efficacy and insurance barriers rather than adverse events 3
Clinical Efficacy Outcomes
For IBS-C (290 mcg dose)
- Significantly improves both abdominal pain (48.9% responders vs 34.5% placebo) and bowel movements (47.6% CSBM responders vs 22.6% placebo) 7
- Number needed to treat: 5.1 for FDA composite endpoint 7
- Improves stool consistency, straining, bloating, and quality of life 2, 7
For CIC (145 mcg dose)
- Increases CSBMs per week by 1.37 compared to placebo 3
- Increases spontaneous bowel movements by 1.97 per week versus placebo 3
- Improves Bristol Stool Scale score by 1.25 points 3
- Triples responder rates compared to placebo (RR 3.14) 3
Treatment Algorithm Position
- Use as second-line therapy after inadequate response to over-the-counter laxatives 3
- Can be used as replacement for or adjunct to OTC agents 3
- Consider particularly for patients with concurrent abdominal symptoms (bloating, discomfort, pain) 3
- If problematic diarrhea occurs, consider dose reduction (for CIC patients, can reduce from 145 mcg to 72 mcg) 3