What is the recommended dosage and administration of Linzess (linaclotide) for irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC)?

Linzess (Linaclotide) Dosing and Administration

For IBS-C, use linaclotide 290 mcg once daily; for CIC, 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)

• The FDA-approved dose is 290 mcg orally once daily 2, 1
• This dosing is supported by high-certainty evidence from 4 randomized controlled trials involving 2,612 patients, demonstrating that 34.0% of patients met the FDA composite endpoint (improvement in both abdominal pain and bowel movements) compared to 18.8% with placebo 2
• The AGA provides a strong recommendation for linaclotide use in IBS-C based on high-quality evidence 2

Chronic Idiopathic Constipation (CIC)

• The standard dose is 145 mcg once daily 1
• An alternative dose of 72 mcg once daily may be used based on individual presentation or tolerability 1
• The AGA recommends linaclotide as a second-line treatment for CIC after failure of over-the-counter laxatives 3
• Both doses significantly improve complete spontaneous bowel movements (CSBMs), with increases of 1.37 CSBMs per week compared to placebo 3

Pediatric Functional Constipation (Ages 6-17)

• The recommended dose is 72 mcg once daily 1

Administration Instructions

Timing and Food Interactions

• Take on an empty stomach at least 30 minutes before the first meal of the day 4, 1
• 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 time 4, 1
• Never take 2 doses at the same time to minimize risk of adverse effects 4

Capsule Administration Options

Standard Administration:

• Swallow capsule whole; do not crush or chew 1

For Patients Unable to Swallow Capsules:

Option 1 - With Applesauce:

• Place one teaspoonful of room-temperature applesauce in a clean container 1
• Open capsule and sprinkle entire contents (beads) on applesauce 1
• Consume entire contents immediately without chewing the beads 1
• Do not store for later use 1

Option 2 - With Water (Oral):

• Pour approximately 30 mL of room-temperature bottled water into a clean cup 1
• Open capsule and sprinkle beads into water 1
• Gently swirl for at least 20 seconds 1
• Swallow entire mixture immediately 1
• Add another 30 mL of water to remaining beads, swirl for 20 seconds, and swallow 1

Option 3 - Via Nasogastric or Gastrostomy Tube:

• Mix beads with 30 mL room-temperature water in clean container 1
• Swirl for at least 20 seconds 1
• Draw up mixture in catheter-tipped syringe 1
• Apply rapid, steady pressure (10 mL/10 seconds) to dispense into tube 1
• Repeat with another 30 mL water for remaining beads 1
• Flush tube with minimum 10 mL water after administration 1

Critical Safety Considerations

Contraindications

• Contraindicated in patients with known or suspected mechanical gastrointestinal obstruction 4, 1

Most Common Adverse Effect

• Diarrhea is the most common adverse event, occurring in 16.3% of patients on linaclotide versus 2.3% on placebo 2
• Diarrhea leads to treatment discontinuation in approximately 3.4-4.5% of patients 2, 5
• The majority (90.5%) of diarrhea cases are mild to moderate 6
• No serious adverse events due to diarrhea have been reported 2

Special Populations

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

Clinical Efficacy Evidence

IBS-C Outcomes

• 48.9% of patients achieve ≥30% reduction in abdominal pain versus 34.5% with placebo 5
• 47.6% achieve CSBM responder criteria versus 22.6% with placebo 5
• Significant improvements in abdominal bloating, straining, and stool consistency 2
• The British Society of Gastroenterology considers linaclotide the most efficacious secretagogue available for IBS-C 2

CIC Outcomes

• Increases spontaneous bowel movements by 1.97 per week compared to placebo 3
• Improves stool consistency by 1.25 points on Bristol Stool Scale 3
• Triples responder rates compared to placebo (RR 3.14) 3

Treatment Duration

• Clinical trials evaluated treatment for 12-26 weeks 2, 3
• Long-term safety studies demonstrate safety for up to 104 weeks 6
• The FDA label does not provide a limit on treatment duration 3