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

Recommended Dosage of Linzess (Linaclotide) for IBS-C and CIC

For patients with irritable bowel syndrome with constipation (IBS-C), the recommended dosage of Linzess (linaclotide) is 290 mcg orally once daily, while for chronic idiopathic constipation (CIC), the recommended dosage is 145 mcg orally once daily, with an option to use 72 mcg once daily based on individual presentation or tolerability. 1

Dosage Recommendations by Condition

For IBS-C:

• Adults: 290 mcg once daily 1
• Not recommended for patients under 18 years with IBS-C 2

For CIC:

• Adults: 145 mcg once daily (standard dose) 1
• Adults: 72 mcg once daily (alternative dose based on tolerability) 1
• Children 6-17 years with functional constipation: 72 mcg once daily 1

Administration Instructions

1. Take Linzess on an empty stomach, at least 30 minutes prior to the first meal of the day 1
2. Take at approximately the same time each day 1
3. Swallow the capsule whole - do not crush or chew 1
4. If a dose is missed, skip it and take the next dose at the regular time - do not take 2 doses at the same time 1

Alternative Administration Methods:

• For patients unable to swallow capsules, Linzess can be opened and administered:
  • With applesauce: Sprinkle contents on one teaspoonful of room-temperature applesauce and consume immediately 1
  • With water: Mix contents with 30 mL of room-temperature water, swirl for at least 20 seconds, and consume immediately 1
  • Via nasogastric or gastrostomy tube: Mix contents with 30 mL of water and administer via syringe 1

Efficacy

Linaclotide has demonstrated significant efficacy in treating both IBS-C and CIC:

• In IBS-C patients, linaclotide significantly improves the FDA composite endpoint with a number needed to treat (NNT) of 5.1 2
• 33.7% of linaclotide-treated patients were FDA endpoint responders versus 13.9% of placebo-treated patients 3
• 48.9% of patients reported ≥30% reduction in abdominal pain compared to 34.5% with placebo 3
• Linaclotide increases complete spontaneous bowel movements (CSBMs) per week with a mean difference of 1.37 compared to placebo 2

Safety Considerations

• Diarrhea is the most common adverse effect, occurring in 16-20% of patients in clinical trials 4, 5
• Most cases of diarrhea (90.5%) are mild to moderate in intensity 5
• Discontinuation due to diarrhea occurs in approximately 4.0% of patients taking linaclotide compared to 0.3% with placebo 5
• Monitor for signs of dehydration, including decreased urination, dry mouth, dizziness, and increased thirst 2

Contraindications

• Contraindicated in children under 6 years of age 2
• Not recommended in patients with known or suspected mechanical gastrointestinal obstruction 2
• Use with caution in elderly patients or those with pre-existing gastrointestinal conditions 2

Clinical Pearls

• If 145 mcg causes intolerable diarrhea in CIC patients, consider reducing to the 72 mcg dose 1, 6
• The 72 mcg dose has been shown to significantly improve CIC symptoms with a lower rate of discontinuation due to diarrhea compared to the 145 mcg dose 6
• Linaclotide acts locally in the GI tract with minimal systemic exposure, resulting in low oral bioavailability and thus a low risk of systemic adverse effects 7
• Avoid combining with docusate as this combination may increase the risk of diarrhea and dehydration 2

Remember that linaclotide works through a novel mechanism as a guanylate cyclase-C agonist that increases intestinal fluid secretion and accelerates transit, making it an important advance in the treatment of both IBS-C and CIC 4.