Source: FDA label
| Molecular formula | C65H104N18O26S4 |
|---|---|
| Molecular weight | 1681.9 g/mol |
| Registered trials | 15 |
| PubChem CID | 70693500 |
| Drug class | Guanylate Cyclase-C Agonist [EPC] |
| Brand names | Trulance Immediate release |
Boxed warning: The FDA label for this compound includes a boxed warning, the FDA's strongest safety warning. See the full prescribing information for details.
Mechanism of Action
12.1 Mechanism of Action Plecanatide is a structural analog of human uroguanylin, and similarly to uroguanylin, plecanatide functions as a guanylate cyclase-C (GC-C) agonist. Both plecanatide 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 of extracellular cGMP has been associated with a de
Key takeaways
- Plecanatide is FDA-approved under the brand name Trulance for two constipation-related conditions in adults.
- It works by activating guanylate cyclase-C on the intestinal lining, a mechanism shared with its natural counterpart, uroguanylin.
- The label carries a boxed warning.
- Across 15 registered trials, studies have covered both chronic idiopathic constipation and IBS-C in adults.
- FAERS reports are led by gastrointestinal symptoms, most often diarrhoea.
What plecanatide is
Plecanatide is a guanylate cyclase-C (GC-C) agonist built as a structural analog of human uroguanylin, a peptide the gut produces naturally. Plecanatide and its active metabolite bind to GC-C receptors on the surface of the intestinal lining. This activation raises cyclic guanosine monophosphate (cGMP) levels inside and outside the cells, a change linked to effects on intestinal fluid and motility.
What plecanatide is approved for
Trulance is approved for adults with chronic idiopathic constipation (CIC) and for adults with irritable bowel syndrome with constipation (IBS-C). The label carries a boxed warning, which prescribers and patients should review directly rather than infer from a summary.
What the evidence shows
Plecanatide has been studied across 15 registered clinical trials. A completed Phase 3 trial, the Second Plecanatide Study in Irritable Bowel Syndrome With Constipation, evaluated the drug specifically in the IBS-C population. An earlier completed Phase 2 dose-ranging study examined plecanatide in patients with chronic idiopathic constipation, helping establish its development path toward approval.
Reported side effects
FAERS data reflect the volume of adverse event reports submitted to regulators, not confirmed incidence or a proven causal link to the drug. The most reported reactions are gastrointestinal: diarrhoea (370 reports), nausea (169), constipation (159), abdominal distension (105), and upper abdominal pain (102). Reports of drug ineffectiveness (159), fatigue (112), and headache (100) also appear among the more frequently logged terms.
FAQ
What is plecanatide used for?
Plecanatide, sold as Trulance, is approved for adults with chronic idiopathic constipation and for adults with irritable bowel syndrome with constipation. It is not approved for use outside these two indications.
How does plecanatide work?
Plecanatide is a lab-made analog of uroguanylin, a peptide the intestine produces naturally. It activates guanylate cyclase-C receptors on the gut lining, raising cGMP levels in a way associated with changes in intestinal fluid and movement.
Does plecanatide have a boxed warning?
Yes, the FDA label for Trulance includes a boxed warning. Anyone considering the medication should review the full prescribing information for the specific details of that warning.
What are the most commonly reported side effects of plecanatide?
The most frequently reported reactions in adverse event data are gastrointestinal, including diarrhoea, nausea, constipation, abdominal distension, and upper abdominal pain. Fatigue and headache are also reported. These figures reflect report counts submitted to a surveillance database, not confirmed rates or proof that the drug caused the reaction.
Has plecanatide been studied in clinical trials?
Yes, plecanatide has been evaluated across 15 registered clinical trials. These include completed Phase 3 research in IBS-C and completed Phase 2 dose-ranging work in chronic idiopathic constipation.
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Content is editorial information, not medical advice. Talk to your doctor before any treatment decision.
Sources: DailyMed label (Trulance) ClinicalTrials.gov FAERS PubChem
Updated 2026-08-03