Linaclotide, sold under the brand name Linzess in the US and Mexico (and Constella elsewhere), is a prescription medication primarily used to treat irritable bowel syndrome with constipation (IBS-C), chronic idiopathic constipation (CIC), and functional constipation in pediatric patients aged 6-17 years. 9 It is an orally administered oligopeptide that acts locally in the gastrointestinal tract with minimal systemic absorption. 9

Medical Uses

• Irritable Bowel Syndrome with Constipation (IBS-C): Linaclotide relieves symptoms such as abdominal pain, bloating, and constipation in adults with IBS-C. 10
• Chronic Idiopathic Constipation (CIC): It is indicated for adults with long-term constipation without a known cause, helping to increase bowel movements and soften stools. 10
• Functional Constipation (in Pediatrics): Approved for children and adolescents aged 6-17 years to treat constipation without an underlying organic cause. 10

Mechanism of Action

Linaclotide is a guanylate cyclase-C (GC-C) agonist that binds to receptors on the surface of intestinal epithelial cells. 9 This binding increases levels of cyclic guanosine monophosphate (cGMP), which stimulates the secretion of chloride and bicarbonate into the intestinal lumen via the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. 10 The result is increased fluid in the intestines, accelerated gastrointestinal transit, and softer stools, without significant absorption into the bloodstream. 10 It is metabolized in the GI tract to an active metabolite and further broken down into amino acids, with excretion primarily in feces. 10

Dosing and Administration

Dosing varies by indication and patient age; capsules are available in 72 mcg, 145 mcg, and 290 mcg strengths. 10 No dosage adjustments are needed for renal or hepatic impairment. 10

• Adults (IBS-C): 290 mcg taken orally once daily. 10
• Adults (CIC): 145 mcg once daily; alternatively, 72 mcg once daily based on individual needs. 10
• Pediatrics Aged 6-17 (Functional Constipation): 72 mcg once daily. 10

Take on an empty stomach at least 30 minutes before the first meal of the day, swallowing the capsule whole (do not chew or crush). 10 For those who have difficulty swallowing, contents can be sprinkled on applesauce or mixed in water. 10 Store at room temperature (25°C/77°F) in the original container with desiccant to protect from moisture. 10

Side Effects

Common side effects include:

• Very Common (>10%): Diarrhea (16-22% in CIC, 20% in IBS-C, 4% in pediatric functional constipation). 10
• Common (1-10%): Abdominal pain (7%), flatulence (4-6%), abdominal distension (2-3%), headache (4%), upper respiratory tract infection (5%), sinusitis (3%), viral gastroenteritis (3%), severe diarrhea (2%), defecation urgency (<2%), fecal incontinence (<2%), vomiting (<2%), and gastroesophageal reflux disease (<2%). 10
• Other (Frequency Not Defined or Postmarketing): Nausea, abdominal discomfort, dehydration, hypersensitivity reactions (e.g., anaphylaxis, angioedema, rash), hematochezia, rectal hemorrhage, decreased appetite, low potassium, orthostatic hypotension, and gastrointestinal bleeding. 9 10

Warnings and Contraindications

Linaclotide carries a black box warning due to the risk of serious dehydration in young children; it is contraindicated in patients under 2 years old and not recommended for those aged 2-5 years. 10 Use caution in children aged 6-17 years. 9 It has not been studied in pregnant women, and its presence in breast milk is unknown. 9 Avoid use if there is a known mechanical gastrointestinal obstruction. 9

Other Information

Linaclotide is a synthetic 14-amino-acid peptide structurally related to bacterial enterotoxins and endogenous hormones like guanylin. 9 It was first approved in 2012 and is marketed by AbbVie (following acquisitions) in the US, with over 2 million prescriptions in 2023, making it the 178th most prescribed medication in the US. 9 No specific drug interactions are widely reported, but consult a healthcare provider for personalized advice. 10 Always discuss with a doctor before starting, as it may not be suitable for everyone.

Disclaimer: Grok is not a doctor; please consult one. Don’t share information that can identify you.