Constella (Linaclotide) Dosing for Chronic Idiopathic Constipation
For chronic idiopathic constipation in adults, start linaclotide at 72 μg or 145 μg once daily, taken on an empty stomach at least 30 minutes before the first meal of the day, with a maximum dose of 290 μg daily if needed for symptom control. 1, 2
Standard Dosing Regimen
Initial Dose
- Start with 72-145 μg once daily for chronic idiopathic constipation 1
- The 72 μg dose is FDA-approved and effective with lower discontinuation rates due to diarrhea (2.4% vs 3.2% for 145 μg) 3
- The 145 μg dose is also FDA-approved for chronic idiopathic constipation 2, 3
Maximum Dose
- 290 μg daily is the maximum approved dose 1
- The 290 μg dose is specifically FDA-approved for irritable bowel syndrome with constipation (IBS-C), though it can be used for chronic constipation when lower doses are insufficient 2, 4
Dose Titration
- Titrate based on symptom response - increase if constipation persists 1
- No specific titration schedule is mandated; adjust according to individual patient response and tolerability 1
Critical Administration Instructions
Timing Relative to Food
- Must be taken on an empty stomach, at least 30 minutes before the first meal of the day 2
- Taking linaclotide immediately after a high-fat breakfast results in looser stools and higher stool frequency compared to the fasted state 2
- This timing requirement is essential because all clinical trials administered the medication in the fasted state 2
Consistency
- Administer at approximately the same time each day 2
Expected Clinical Response
Efficacy Timeline
- Improvement in bowel movements typically occurs within the first week of treatment 3
- Full therapeutic benefit is generally assessed over 12 weeks 1, 3
Specific Improvements
- Increases complete spontaneous bowel movements (CSBMs) by approximately 1.37 per week compared to placebo 1
- Improves stool consistency significantly (mean difference 1.25 on Bristol Stool Scale) 1
- May reduce abdominal pain and bloating, particularly at the 290 μg dose used for IBS-C 1, 4
Safety Profile and Side Effects
Most Common Adverse Effect
- Diarrhea is the most frequent side effect, occurring in a dose-dependent manner 1, 2, 3
- Diarrhea is typically mild and leads to discontinuation in only 0% (placebo), 2.4% (72 μg), and 3.2% (145 μg) of patients 3
- At the 290 μg dose, approximately 4.7% discontinue due to diarrhea 1
Systemic Safety
- Linaclotide has negligible systemic absorption - plasma concentrations are below the limit of quantitation after oral administration 2
- This results in minimal risk of systemic adverse effects 4
- No dose adjustment needed for renal or hepatic impairment because metabolism occurs within the gastrointestinal tract 2
Contraindications
Absolute Contraindications
- Do not use in patients with known or suspected mechanical gastrointestinal obstruction 1, 2
- Contraindicated in pediatric patients younger than 6 years (risk of serious dehydration) 2
Special Populations
Pediatric Patients (Ages 6-17)
- 72 μg once daily is the approved dose for functional constipation in children aged 6-17 years 5
- Demonstrated significant improvement in spontaneous bowel movement frequency (increase of 2.22 SBMs per week vs 1.05 for placebo) 5
- Generally well tolerated, though one case of severe diarrhea with dehydration requiring hospitalization occurred in a 17-year-old patient 5
Elderly Patients
- Efficacy in persons 65 years and older is comparable to the overall study population 1
- No dose adjustment required 2
Clinical Pearls
When to Consider Linaclotide
- Use when over-the-counter laxatives (polyethylene glycol, fiber, osmotic agents) have failed 1
- Consider earlier if patient has coexisting abdominal pain or bloating, as linaclotide addresses these symptoms 1, 4
Duration of Therapy
- Clinical trials evaluated treatment for 12 weeks, but the FDA label does not specify a treatment duration limit 1, 2
- Long-term use (18 months) has been shown to be effective and safe in real-world clinical settings 6