What is the initial dosage of Linzess (linaclotide)?

Initial Dosage of Linzess (Linaclotide)

The initial dosage of Linzess depends on the indication: 290 mcg once daily for IBS-C in adults, 145 mcg once daily for CIC in adults (with 72 mcg as an alternative based on tolerability), and 72 mcg once daily for functional constipation in pediatric patients ages 6-17 years. 1

Dosing by Indication

Irritable Bowel Syndrome with Constipation (IBS-C) in Adults

• Start with 290 mcg orally once daily 1
• This dose was consistently used across multiple high-quality trials demonstrating significant improvements in the FDA composite endpoint (≥30% reduction in abdominal pain AND ≥1 complete spontaneous bowel movement increase per week) 2
• The 290 mcg dose achieved responder rates of 33.6-33.7% vs. 13.9-21.0% for placebo in pivotal trials 3, 4

Chronic Idiopathic Constipation (CIC) in Adults

• Start with 145 mcg once daily OR 72 mcg once daily 1
• The 145 mcg dose is the standard starting dose for CIC 5, 1
• The 72 mcg dose may be used initially based on individual presentation or tolerability concerns 1
• Both doses significantly improved bowel movements: the 72 mcg dose achieved 13.4% responder rate vs. 4.7% placebo, while 145 mcg achieved 12.4% vs. 4.7% placebo 6
• Consider starting with 72 mcg in patients concerned about diarrhea risk, as discontinuation due to diarrhea was 0% with 72 mcg vs. 2.4-3.2% with 145 mcg 6

Functional Constipation in Pediatric Patients (Ages 6-17)

• 72 mcg once daily 1
• This is the only approved dose for this population 1

Critical Administration Instructions

Timing and Food Interactions

• Take on an empty stomach at least 30 minutes before the first meal of the day 7, 1
• Taking with food significantly reduces efficacy 7
• Administer at approximately the same time each day for consistency 1

Capsule Handling

• Do not crush or chew the capsule or its contents 1
• Swallow capsules whole whenever possible 1
• For patients unable to swallow capsules, the capsule may be opened and contents administered in applesauce or water, or via nasogastric/gastrostomy tube following specific preparation instructions 1

Missed Dose Protocol

• If a dose is missed, skip it and take the next dose at the regular scheduled time 7, 1
• Never take 2 doses at the same time to avoid increased risk of adverse effects 7, 1

Safety Considerations at Initiation

Absolute Contraindications

• Patients under 2 years of age due to risk of fatal dehydration 1
• Known or suspected mechanical gastrointestinal obstruction 7, 1

Expected Adverse Effects

• Diarrhea is the most common adverse effect across all doses 5, 8, 3, 4
• Diarrhea rates: 6% with 145 mcg, 17% with 290 mcg vs. 2% with placebo in CIC patients 8
• In IBS-C trials, diarrhea led to discontinuation in 4.5-5.7% of patients on 290 mcg vs. 0.2-0.3% on placebo 3, 4
• Most diarrhea is mild and controllable by dose reduction 9

Clinical Context from Guidelines

The American Gastroenterological Association (2022) and British Society of Gastroenterology (2021) both recommend linaclotide as a second-line agent after failure of first-line therapies 2:

• For IBS-C: Use after inadequate response to dietary modifications and first-line agents 2
• For CIC: Use after inadequate response to over-the-counter laxatives 5
• Linaclotide is considered the most efficacious secretagogue available for IBS-C and CIC 2