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 290 mcg once daily; for CIC, use 145 mcg once daily (or 72 mcg based on tolerability); always take on an empty stomach at least 30 minutes before the first meal of the day. 1

Dosing by Indication

Irritable Bowel Syndrome with Constipation (IBS-C)

• 290 mcg orally once daily is the FDA-approved and guideline-recommended dose for adults with IBS-C 2, 1
• This dose demonstrates robust efficacy, with 34.0% of patients meeting the FDA composite endpoint (improvement in both abdominal pain and complete spontaneous bowel movements) versus 18.8% with placebo 2
• The American Gastroenterological Association provides a strong recommendation with high-quality evidence supporting this dose 2

Chronic Idiopathic Constipation (CIC)

• 145 mcg orally once daily is the standard recommended dose for adults with CIC 1
• 72 mcg orally once daily may be used as an alternative based on individual presentation or tolerability concerns 3, 1
• Both doses significantly increase complete spontaneous bowel movements (CSBMs) by 1.37 per week compared to placebo and improve stool consistency 3

Pediatric Functional Constipation (Ages 6-17)

• 72 mcg orally once daily is approved for functional constipation in pediatric patients 6 to 17 years of age 1

Critical Administration Instructions

Timing and Food Interactions

• Must be taken on an empty stomach at least 30 minutes before the first meal of the day 4, 1
• Taking with food significantly reduces efficacy 4
• Should be taken at approximately the same time each day for consistency 1

Capsule Handling

• Swallow capsules whole—do not crush or chew the capsule or its contents 1
• If a dose is missed, skip it and take the next dose at the regular time; never take 2 doses at the same time 4, 1

Alternative Administration Methods

For patients unable to swallow capsules whole 1:

With applesauce:

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

With water (oral):

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

Via nasogastric or gastrostomy tube:

• Mix beads with 30 mL room-temperature water, swirl for 20 seconds
• Draw mixture into catheter-tipped syringe
• Apply rapid, steady pressure (10 mL/10 seconds) to dispense into tube
• Repeat with additional 30 mL water for remaining beads
• Flush tube with minimum 10 mL water after administration

Safety Considerations and Contraindications

Absolute Contraindications

• Patients less than 2 years of age due to risk of serious dehydration and death (Black Box Warning) 1
• Known or suspected mechanical gastrointestinal obstruction 4, 1

Common Adverse Effects

• Diarrhea is the most common adverse event, occurring in 16.3% of patients versus 2.3% with placebo 2
• Diarrhea leads to discontinuation in approximately 3.4-4.5% of patients 2, 5, 6
• Most diarrhea episodes (90.5%) are mild to moderate in severity 5
• If severe diarrhea occurs, suspend dosing and rehydrate the patient 1

Long-term Safety Profile

• In studies extending up to 104 weeks, the safety profile remained consistent with short-term trials 5
• Serious adverse events are rare and similar across treatment groups 5
• No serious adverse events of diarrhea have been reported 2, 5

Clinical Efficacy Context

IBS-C Outcomes

• Significantly improves abdominal pain, with 48.9% of patients achieving ≥30% reduction versus 34.5% with placebo 6
• Increases CSBMs, with 47.6% meeting responder criteria versus 22.6% with placebo 6
• Improves abdominal bloating, stool consistency, and straining 2
• The British Society of Gastroenterology considers linaclotide the most efficacious secretagogue available for IBS-C 2

CIC Outcomes

• Triples responder rates compared to placebo (RR 3.14) 3
• Increases spontaneous bowel movements by 1.97 per week versus placebo 3
• May improve quality of life scores 3

Treatment Algorithm Position

• Second-line therapy after failure of over-the-counter laxatives for both IBS-C and CIC 2, 3
• Can be used as replacement for or adjunct to OTC agents 3
• Particularly appropriate for patients with concurrent abdominal symptoms (bloating, discomfort, pain) 3
• Clinical response at week 4 predicts sustained response at week 12 7

Special Populations

Older Adults

• Efficacy appears similar in patients over 65 years compared to general population, though sample sizes were limited 3

Patients on Diuretics

• May be at higher risk of hyponatremia when taking concurrent medications affecting sodium balance 3