Diagnosis and Management of Pediatric Functional Constipation and Adult Chronic Idiopathic Constipation

Linaclotide Indications, Important Safety Information, and Boxed Warning

INDICATIONS AND USAGE
Linaclotide is indicated for the treatment of:

• Irritable bowel syndrome with constipation (IBS-C) in adults
• Chronic idiopathic constipation (CIC) in adults
• Functional constipation (FC) in pediatric patients 6 to 17 years of age

IMPORTANT SAFETY INFORMATION AND BOXED WARNING

WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE.

Linaclotide 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.

Contraindications

• Linaclotide is contraindicated in patients less than 2 years of age due to the risk of serious dehydration.
• Linaclotide is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

Warnings and Precautions Risk of Serious Dehydration in Pediatric Patients Less Than 2 Years of Age

• Linaclotide is contraindicated in patients less than 2 years of age. In neonatal mice, linaclotide increased fluid secretion as a consequence of age-dependent elevated guanylate cyclase (GC-C) agonism, which was associated with increased mortality within the first 24 hours due to dehydration. There was no age-dependent trend in GC-C intestinal expression in a clinical study of children 2 to less than 18 years of age; however, there are insufficient data available on GC-C intestinal expression in children less than 2 years of age to assess the risk of developing diarrhea and its potentially serious consequences in these
  patients.

Diarrhea

• In adults, diarrhea was the most common adverse reaction in Linaclotide-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar in the IBS-C and CIC populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg Linaclotide-treated patients and in <1% of 72 mcg Linaclotide-treated CIC patients. In pediatric patients 6 to 17 years of age, diarrhea was the most common adverse reaction in 72 mcg Linaclotide-treated patients in the FC double-blind placebo-controlled trial. Severe diarrhea was reported in one Linaclotide-treated patient. If severe diarrhea occurs, dosing should be suspended and the patient rehydrated.

Common Adverse Reactions (incidence ≥2% and greater than placebo)

• In IBS-C or CIC adult patients: diarrhea, abdominal pain, flatulence, and abdominal distension.
• In FC pediatric patients: diarrhea.

Review accompanying linaclotide full Prescribing Information for additional information, visit www.rxabbvie.com or contact AbbVie Medical Information at 1-800-633-9110.