Linzess®Linaclotide Capsules

1. Indications and Usage
Linaclotide is indicated for the treatment of adults with:
Irritable Bowel Syndrome with Constipation (IBS-C) .
Chronic Idiopathic Constipation (CIC) .
2. Dosage and Administration
IBS-C: The recommended dose is 290 mcg taken orally once daily .
CIC: The recommended dose is 145 mcg taken orally once daily .
Administration: Capsules should be swallowed whole at least 30 minutes before the first meal of the day. Do not break or chew the capsules .
3. Mechanism of Action
Linaclotide is a guanylate cyclase-C (GC-C) agonist.
It binds to GC-C receptors on the luminal surface of the intestinal epithelium, increasing intracellular and extracellular cyclic guanosine monophosphate (cGMP). This stimulates the secretion of chloride and bicarbonate ions into the intestinal lumen via the CFTR ion channel, increasing intestinal fluid and accelerating transit.
Additionally, elevated extracellular cGMP decreases the activity of pain-sensing nerves, reducing visceral pain .
4. Safety and Warnings
Contraindications: Known or suspected mechanical gastrointestinal obstruction; Hypersensitivity to linaclotide or any ingredient; Children up to 6 years of age .
Pediatric Risk: Use should be avoided in pediatric patients 6 through 17 years of age due to the risk of severe dehydration observed in nonclinical studies, which caused mortality in young juvenile mice .
Diarrhea: Diarrhea is the most common adverse reaction. If severe diarrhea occurs, treatment should be discontinued immediately .
5. Adverse Reactions
The most common adverse reaction (≥2%) is diarrhea. Other reported reactions include abdominal pain, flatulence, abdominal distension, headache, and viral gastroenteritis .
6. Drug Interactions
Systemic exposure to linaclotide is negligible. No formal drug interaction studies have been performed, but interactions involving CYP enzymes or P-glycoprotein are unlikely.
However, co-administration with proton pump inhibitors, laxatives, or NSAIDs may increase the risk of diarrhea. It may also decrease the absorption of other oral medications (e.g., oral contraceptives, levothyroxine) due to increased intestinal transit .
7. Pharmaceutical Information
Chemical Name: L-cysteinyl-L-cysteinyl-L-glutamyl-L-tyrosyl-L-cysteinyl-L-cysteinyl-L-asparaginyl-L-prolyl-L-alanyl-L-cysteinyl-L-threonyl-glycyl-L-cysteinyl-L-tyrosine, cyclic (1–6),(2–10),(5–13)-tris (disulfide) .
Molecular Formula: C59H79N15O21S6 .
Molecular Weight: 1526.8 .
Storage: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) .