What is the treatment regimen for an adult patient with constipation or irritable bowel syndrome with constipation using Linzess (linaclotide)?

Linzess (Linaclotide) Treatment Regimen

For adults with irritable bowel syndrome with constipation (IBS-C), use Linzess 290 mcg orally once daily; for chronic idiopathic constipation (CIC), use 145 mcg once daily (or 72 mcg once daily based on tolerability). 1

Dosing by Indication

IBS-C in Adults

• 290 mcg orally once daily is the FDA-approved and guideline-recommended dose 2, 1
• This dose achieved a 34.0% responder rate versus 18.8% with placebo across 4 high-quality RCTs 2
• The American Gastroenterological Association provides a strong recommendation with high certainty evidence for linaclotide in IBS-C 2

CIC in Adults

• 145 mcg orally once daily is the standard starting dose 1, 3
• 72 mcg once daily may be used as an alternative based on individual presentation or tolerability concerns 1, 3
• This represents a strong recommendation with high certainty evidence from the AGA 3

Administration Instructions

Timing and Method

• Take on an empty stomach at least 30 minutes before the first meal of the day, at approximately the same time each day 1, 3
• 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 simultaneously 1

Alternative Administration for Patients Unable to Swallow

• For patients who cannot swallow capsules whole, open the capsule and administer the beads either:
  • Mixed with one teaspoonful of room-temperature applesauce (consume immediately, do not chew beads) 1
  • Mixed with 30 mL of room-temperature water (swirl for 20 seconds, swallow immediately) 1
  • Via nasogastric or gastrostomy tube with water using rapid, steady pressure 1

Clinical Efficacy Evidence

IBS-C Benefits

• 34.8% of patients met the FDA composite endpoint (improvement in both abdominal pain and bowel movements) versus 21.3% with placebo 2
• 60.0% achieved ≥30% reduction in abdominal pain/discomfort compared to 48.8% with placebo 2
• Significantly improved complete spontaneous bowel movements (CSBMs) with RR 0.86 (95% CI, 0.83-0.89) 2
• 31.7% reported being "considerably relieved" or "completely relieved" versus 15.4% with placebo 2

CIC Benefits

• Increases CSBMs by 1.37 per week compared to placebo 3
• 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

Safety Profile and Adverse Effects

Diarrhea Management

• Diarrhea is the most common adverse effect, occurring in 16.3% of IBS-C patients (versus 2.3% placebo) 2
• 3.4% of patients discontinue due to diarrhea versus 0.2% with placebo 2
• No serious adverse events or deaths due to diarrhea were reported in clinical trials 2
• If severe diarrhea occurs, suspend dosing and rehydrate the patient 1
• Consider dose reduction from 145 mcg to 72 mcg if diarrhea is problematic in CIC patients 3, 4

Contraindications

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

Treatment Algorithm and Clinical Context

When to Use Linaclotide

• Start with over-the-counter laxatives as first-line therapy for CIC 3, 4
• Add or switch to linaclotide when patients do not respond adequately to OTC agents 3, 4
• Linaclotide can be used as replacement for or adjunct to OTC agents (including PEG-based laxatives like Movicol) 4
• Particularly useful for patients with concurrent abdominal symptoms (bloating, discomfort, pain) due to its dual mechanism of action 4

Duration of Treatment

• Clinical trials evaluated 12-week treatment periods 2, 3
• The FDA label does not provide a limit on treatment duration, allowing for long-term use if effective and well-tolerated 3, 4

Mechanism of Action

• Linaclotide is a guanylate cyclase-C agonist that increases cyclic guanosine monophosphate concentrations 3
• This results in luminal chloride and bicarbonate secretion, increasing intestinal fluid and accelerating gastrointestinal transit 3
• In animal models, it also inhibits colonic nociceptors, which may explain pain reduction 2
• The drug is minimally absorbed systemically, acting locally in the gastrointestinal tract 2

Common Pitfalls to Avoid

• Do not administer with food—this reduces efficacy; ensure 30+ minute gap before meals 1
• Do not start both linaclotide and OTC laxatives simultaneously in treatment-naive patients to avoid excessive response 4
• Monitor for excessive response requiring dose adjustment, particularly in the first few weeks 4
• Ensure proper patient counseling about the expected timeline for response (clinical response at week 4 predicts sustained response at week 12) 5