What is the recommended dose of Constella (linaclotide) for an adult patient with constipation or irritable bowel syndrome with constipation?

Constella (Linaclotide) Dosing

For irritable bowel syndrome with constipation (IBS-C) in adults, the recommended dose is 290 mcg orally once daily, and for chronic idiopathic constipation (CIC) in adults, the recommended dose is 145 mcg once daily (or 72 mcg once daily based on tolerability). 1

Dosing by Indication

IBS-C (Adults)

• 290 mcg once daily is the established dose, consistently demonstrating significant improvements in the FDA composite endpoint (≥30% reduction in abdominal pain AND ≥1 complete spontaneous bowel movement increase per week for at least 6 of 12 weeks) 2, 1
• This dose achieved responder rates of 33.6-33.7% versus 13.9-21.0% for placebo across multiple high-quality trials 3, 4, 5
• The number needed to treat is approximately 5-8 patients 4, 5

CIC (Adults)

• 145 mcg once daily is the standard starting dose 3, 1
• 72 mcg once daily is an alternative dose based on individual presentation or tolerability concerns 3, 1
• Both doses significantly improve complete spontaneous bowel movements, stool consistency, and quality of life 3

Functional Constipation (Pediatric Patients 6-17 years)

• 72 mcg once daily is the recommended dose 1

Administration Instructions

• Take on an empty stomach at least 30 minutes before the first meal of the day at approximately the same time each day 3, 1
• Do not crush or chew the capsule or capsule contents 1
• For patients with difficulty swallowing, capsules can be opened and administered with applesauce or water 1

Treatment Duration and Response Assessment

• Clinical trials evaluated treatment over 12 weeks, though the FDA label does not limit treatment duration 3
• Clinical response at week 4 predicts sustained response at week 12 (odds ratio 6.5), so continue treatment through 12 weeks as late responses occur, particularly if patients show improvement in at least some symptoms 6, 7
• Sustained efficacy has been demonstrated over 26 weeks of treatment 4

Safety Considerations

Common Adverse Effects

• Diarrhea is the most common adverse effect, occurring in approximately 16.3-35.4% of patients versus 2.3% with placebo 8, 7, 4
• Diarrhea leads to treatment discontinuation in approximately 4.5-5.7% of patients versus 0.2-0.3% with placebo 4, 5
• Other common adverse reactions (≥2%) include abdominal pain, flatulence, and abdominal distension 1

Management of Diarrhea

• If severe diarrhea occurs, suspend dosing and rehydrate the patient 1
• Consider dose reduction if diarrhea is problematic 3

Contraindications

• Absolutely contraindicated in patients less than 2 years of age due to risk of serious dehydration and death (boxed warning) 1
• Contraindicated in patients with known or suspected mechanical gastrointestinal obstruction 1

Special Populations

• Efficacy appears similar in patients over 65 years of age, though sample sizes were limited 3
• Patients on concurrent diuretics may be at higher risk of electrolyte disturbances 3

Clinical Efficacy Beyond Primary Endpoints

• Linaclotide significantly improves multiple abdominal symptoms including bloating, discomfort, and pain (mean reduction of -1.9 versus -1.2 for placebo) 9
• Improves stool consistency by 1.25 points on Bristol Stool Scale 3
• Increases spontaneous bowel movements by 1.97 per week compared to placebo 3
• May improve quality of life scores 3, 10