Linaclotide

LINZESS is indicated for the treatment of: • irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older • chronic idiopathic constipation (CIC) in adults • functional constipation (FC) in pediatric patients 2 years of age and older LINZESS is a guanylate cyclase-C agonist indicated for treatment of: Irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older. Chronic idiopathic constipation (CIC) in adults. Functional constipation (FC) in pediatric patients 2 years of age and older.

Linaclotide is structurally related to human guanylin and uroguanylin and functions as a guanylate cyclase-C (GC-C) agonist. Both linaclotide and its active metabolite bind to GC-C and act locally on the luminal surface of the intestinal epithelium. Activation of GC-C results in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP). Elevation in intracellular cGMP stimulates secretion of chloride and bicarbonate into the intestinal lumen, mainly through activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, resulting in increased intestinal fluid and accelerated transit. In animal models, linaclotide has been shown to both accelerate GI transit and reduce intestinal pain.

The recommended dosage in adults is: IBS-C: 290 mcg orally once daily. CIC: 145 mcg orally once daily or 72 mcg orally once daily based on individual presentation or tolerability. The recommended dosage in pediatric patients: 7 years of age and older with IBS-C: 145 mcg orally once daily. 2 years of age and older with FC: 72 mcg orally once daily. Administration Instructions: Take on empty stomach at least 30 minutes prior to a meal at approximately the same time each day. Do not crush or chew LINZESS capsule or capsule contents. For patients who have difficulty swallowing capsules whole or those with a nasogastric or gastrostomy tube, see full prescribing information for instructions for opening the capsule and administering with applesauce or water.

LINZESS is contraindicated in: Patients less than 2 years of age due to the risk of serious dehydration. Patients with known or suspected mechanical gastrointestinal obstruction. Patients less than 2 years of age.

Boxed warning: is contraindicated in patients less than 2 years of age, in nonclinical studies in neonatal mice, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration. WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE LINZESS is contraindicated in patients less than 2 years of age, in neonatal mice, linaclotide caused deaths due to dehydration. Diarrhea: Patients may experience severe diarrhea. If severe diarrhea occurs, suspend dosing and rehydrate the patient. Risk of Serious Dehydration in Pediatric Patients Less Than 2 Years of Age LINZESS is contraindicated in patients less than 2 years of age.

Most common adverse reactions (≥2%) reported in adult patients with IBS-C or CIC are: diarrhea, abdominal pain, flatulence and abdominal distension. Most common adverse reaction (≥2%) reported in pediatric patients 7 to 17 years of age with IBS-C and 6 to 17 years of age with FC is diarrhea.

Storage Store at 25°C (77°F), excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from moisture.