Plecanatide

• Chronic Idiopathic Constipation
• Irritable Bowel Syndrome with Constipation
• Functional Constipation

Plecanatide is a guanylate cyclase-C (GC-C) agonist used to treat chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). It works locally in the intestine to increase fluid secretion and accelerate intestinal transit with minimal systemic absorption.

Mechanism of Action

Plecanatide acts in the gastrointestinal tract through receptor activation:

• GC-C receptor agonism: Binds to guanylate cyclase-C receptors on the luminal surface of intestinal epithelial cells
• Increases intracellular cyclic GMP: Activates downstream signaling cascades
• Stimulates CFTR chloride channels: Opens chloride channels, increasing chloride and bicarbonate secretion
• Increases intestinal fluid: Softens stool and accelerates colonic transit
• pH-sensitive activation: More active in the slightly acidic environment of the proximal small intestine

Plecanatide is a synthetic analog of uroguanylin, an endogenous peptide hormone that naturally regulates intestinal fluid balance.

Available Formulations

Plecanatide is available as oral tablets:

• 3 mg tablets (Trulance)

Tablets can be swallowed whole or crushed in applesauce or dissolved in water for patients with swallowing difficulties.

Medical Uses

FDA-Approved Indications:

• Chronic idiopathic constipation (CIC) in adults
• Irritable bowel syndrome with constipation (IBS-C) in adults

Both conditions share symptoms of infrequent bowel movements, straining, hard stools, and sensation of incomplete evacuation.

Dosing Guidelines

Adults (CIC and IBS-C):

• 3 mg once daily with or without food

Administration Options:

• Swallow tablet whole with water
• Crush tablet and mix with room temperature applesauce for immediate consumption
• Crush and disperse in 30 mL water, swirl for 10 seconds and drink immediately

No dose adjustments needed for hepatic or renal impairment due to minimal systemic absorption.

Important Safety Information

Black Box Warning:

• Contraindicated in patients less than 6 years of age: Risk of serious dehydration based on juvenile animal studies
• Avoid use in patients 6 to less than 18 years of age: Safety and efficacy not established in pediatric patients

Contraindications:

• Patients less than 6 years of age
• Known or suspected mechanical gastrointestinal obstruction

Warnings and Precautions:

• Diarrhea: Can be severe; advise patients to stop treatment and contact healthcare provider if severe diarrhea occurs
• Dehydration: Monitor fluid status, especially in elderly patients

Drug Interactions

No formal drug interaction studies have been conducted. Due to minimal systemic absorption (undetectable plasma levels at therapeutic doses), clinically significant drug interactions are not expected.

Special Populations

• Hepatic Impairment: No dose adjustment required due to minimal systemic exposure
• Renal Impairment: No dose adjustment required due to lack of renal elimination
• Pregnancy: Limited human data available; animal studies showed no fetal harm at doses up to 100x human dose
• Lactation: Unknown if excreted in breast milk; minimal systemic absorption suggests low risk
• Pediatric: Contraindicated in patients <6 years; avoid in patients 6-18 years
• Elderly: No dose adjustment needed; monitor for dehydration