Plecanatide

Summary

Plecanatide (Trulance) is a synthetic 16-amino acid peptide analogue of uroguanylin approved for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) in adults. It works locally in the gut with minimal systemic absorption.

Mechanism of Action

Binds and activates guanylate cyclase-C receptors on the luminal surface of intestinal epithelial cells, increasing intracellular cGMP, which activates CFTR chloride channels, leading to increased fluid and electrolyte secretion into the intestinal lumen, accelerating intestinal transit and reducing visceral pain signaling.

Routes of Administration

Goals & Uses

• Abdominal pain/discomfort reduction in IBS-CPain / Symptom ManagementModerate
• Stool consistency improvementGastrointestinalHigh
• Relief of chronic idiopathic constipation (CIC)GastrointestinalHigh
• Relief of irritable bowel syndrome with constipation (IBS-C)GastrointestinalHigh

Contraindications

• Known or suspected mechanical gastrointestinal obstructionGastrointestinalHigh
• Hypersensitivity to plecanatide or any excipientAllergic/ImmunologicHigh
• Pediatric patients under 6 years of ageAge RelatedHigh

Adverse Effects

• Abdominal distensionGastrointestinalUncommon
• NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
• Upper respiratory tract infectionInfectiousUncommon
• DiarrheaGastrointestinalCommonLoose or frequent stools
• DehydrationFluid BalanceRareLoss of body water or inadequate hydration

Drug Interactions

• No clinically significant drug interactions identifiedLow

Population Constraints

• PregnancyReproductive SafetyRelative
• Severe diarrheaGastrointestinalRelative
• Pediatric patients (6 to <18 years)PediatricAbsolute
• BreastfeedingReproductiveRelative

Regulatory Status

• European UnionUnapprovedNot approved by EMA as of knowledge cutoff.
• United StatesApprovedApproved: Chronic idiopathic constipation (CIC) in adults, Irritable bowel syndrome with constipation (IBS-C) in adultsFDA approved January 2017 (CIC) and January 2018 (IBS-C); NDA 208745; boxed warning for pediatric use.
• United KingdomUnapprovedNot approved by MHRA as of knowledge cutoff.

FDA approved January 2017 for CIC; expanded approval for IBS-C in January 2018. Carries a boxed warning contraindicating use in pediatric patients under 6 years due to risk of serious dehydration. Not approved in EU or UK as of knowledge cutoff.

Evidence & Sources

No sources recorded yet.