What is the recommended dosing for Linzess (linaclotide) in adults with constipation or irritable bowel syndrome with constipation, particularly those with impaired renal function?

Linzess Dosing

For IBS-C in adults, use 290 mcg orally once daily; for chronic idiopathic constipation (CIC) in adults, use 145 mcg once daily (or 72 mcg once daily based on tolerability); for functional constipation in pediatric patients 6-17 years, use 72 mcg once daily. 1

Dosing by Indication

Irritable Bowel Syndrome with Constipation (IBS-C)

• 290 mcg orally once daily is the recommended dose for adults with IBS-C 1
• This dose has been validated in multiple high-quality trials, achieving responder rates of 33.6-33.7% versus 13.9-21.0% for placebo on the FDA composite endpoint 2
• The FDA composite endpoint requires both ≥30% improvement in abdominal pain AND ≥1 complete spontaneous bowel movement (CSBM) increase per week for at least 6 out of 12 weeks 3
• The British Society of Gastroenterology identifies linaclotide 290 mcg once daily as likely the most efficacious secretagogue available for IBS-C, though diarrhea is a common side effect 4

Chronic Idiopathic Constipation (CIC)

• 145 mcg once daily is the standard dose for adults with CIC 1
• 72 mcg once daily may be used as an alternative based on individual presentation or tolerability concerns 1
• The American Gastroenterological Association strongly recommends linaclotide as second-line treatment for CIC after failure of over-the-counter laxatives 2
• At 145 mcg, responder rates are 12.4% versus 4.7% for placebo 2

Pediatric Functional Constipation

• 72 mcg once daily for patients aged 6-17 years 1

Administration Instructions

Timing and Food Interactions

• Take on an empty stomach at least 30 minutes before the first meal of the day, at approximately the same time each day 1, 5
• Taking with food significantly reduces efficacy 5

Missed Dose Protocol

• If a dose is missed, skip it and take the next dose at the regular time 1
• Never take 2 doses at the same time 1, 5

Capsule Administration Options

• Swallow capsules whole; do not crush or chew 1
• For patients unable to swallow capsules whole, three alternative methods are available 1:

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 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 entire contents into water 1
• Gently swirl beads and water for at least 20 seconds 1
• Swallow entire mixture immediately 1
• Add another 30 mL of water to any remaining beads, swirl for 20 seconds, and swallow immediately 1
• Note: The drug dissolves off the beads into water; beads remain visible but it is not necessary to consume all beads to deliver the complete dose 1

Option 3 - Via Nasogastric or Gastrostomy Tube:

• Open capsule and empty beads into 30 mL of room-temperature bottled water 1
• Mix by gently swirling for at least 20 seconds 1
• Draw up mixture into catheter-tipped syringe and apply rapid, steady pressure (10 mL/10 seconds) to dispense into tube 1
• Add another 30 mL of water to remaining beads and repeat 1
• Flush tube with minimum of 10 mL of water after administration 1

Treatment Duration and Response Assessment

• Clinical trials typically evaluated treatment over 12 weeks, but the FDA label does not provide a limit on treatment duration 2
• Clinical response at week 4 predicts sustained response at week 12 (OR: 6.5; 95% CI: 2.1-19.8) 6
• This early assessment can guide continuation decisions 6
• Treatment satisfaction and quality of life scores improve progressively over 12 weeks 7

Safety Profile and Adverse Effects

Common Adverse Effects

• Diarrhea is the most common adverse effect, occurring in 10-20% of patients 2, 8, 7
• In real-world Chinese data, diarrhea occurred in 10.0% of patients, with no severe cases reported 7
• Approximately 4.5-4.7% of patients discontinue treatment due to diarrhea 2, 3
• Patients are about 3 times more likely to experience diarrhea leading to discontinuation compared with placebo 2
• Most adverse events are mild (89.9%) and confined to the gastrointestinal tract 7, 8

Contraindications

• Contraindicated in patients with known or suspected mechanical gastrointestinal obstruction 5, 2

Special Populations

• Efficacy appears similar in patients over 65 years of age, though sample sizes in studies were limited 2
• Patients on concurrent diuretics or other medications affecting sodium balance may be at higher risk of hyponatremia 2

Clinical Context and Treatment Algorithm

When to Use Linaclotide

• Start with over-the-counter laxatives as first-line therapy for both IBS-C and CIC 2
• For inadequate response to OTC agents, escalate to linaclotide as second-line treatment 2, 4
• Linaclotide can be used as replacement for or adjunct to OTC agents 2
• Consider linaclotide particularly for patients with concurrent abdominal symptoms (bloating, discomfort, pain) 2
• The drug improves not only bowel function but also abdominal pain, bloating, and overall symptom severity 9, 3

Dose Adjustment Strategy

• If diarrhea occurs and is problematic, consider dose reduction 2
• For CIC patients, this means reducing from 145 mcg to 72 mcg daily 1
• Loss of efficacy and insurance coverage barriers are more common reasons for discontinuation over the first year than adverse events 2

Mechanism Supporting Dosing

• Linaclotide is a guanylate cyclase-C agonist that increases cyclic guanosine monophosphate, resulting in luminal chloride and bicarbonate secretion 2, 8
• This increases intestinal fluid and accelerates gastrointestinal transit 2, 8
• The drug is minimally absorbed into systemic circulation, with effects confined primarily to the gastrointestinal tract 8

Renal Function Considerations

• The evidence provided does not indicate dose adjustments are required for impaired renal function, as linaclotide is minimally absorbed systemically 8
• However, patients on diuretics (which may be used in renal disease) should be monitored for hyponatremia 2