Plecanatide

Trulance, SP-304

Recovery, repair & tissue

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Plecanatide is an approved oral prescription medicine for chronic constipation and constipation-type IBS in adults. It acts only inside the gut and is not absorbed, so it has no relevance as a systemic research peptide. Use outside the label, including in children, is off-label and in young children is specifically warned against. This page explains the published science.

Summary

Class: Synthetic 16-amino-acid peptide; an analogue of human uroguanylin with a single amino-acid change (aspartate to glutamate at position 3)
Mechanism: Activates guanylate cyclase-C on the gut lining, raising cGMP, which pushes chloride and water into the bowel and softens stool; cGMP also damps visceral pain nerves
Routes studied: Oral tablet only
Half-life: Not measurable; plasma levels are below detection after oral dosing because the peptide acts locally and is degraded in the gut
Storage: Room temperature in the original bottle with desiccant; protect from moisture. Tablets may be crushed in applesauce or dispersed in water for people who cannot swallow them
Regulatory status: Approved in the US (2017, 2018) and Canada; not authorised in the EU, UK or Australia

Doses are as reported in studies or by the community — never recommendations.

1What it is

Plecanatide is a near-copy of uroguanylin, one of two small peptides (the other is guanylin) that the gut lining releases after a meal to tell the intestine to secrete fluid. Uroguanylin works best in the slightly acidic environment of the upper small intestine; plecanatide's one substitution was designed to keep that pH-sensitivity and improve stability. It was developed by Synergy Pharmaceuticals, approved by the FDA in January 2017 for chronic idiopathic constipation (CIC) and in January 2018 for irritable bowel syndrome with constipation (IBS-C). Synergy went bankrupt in 2019 and the product passed to Bausch Health (Salix).

It is the second drug in its class after linaclotide (Linzess/Constella), which copies a bacterial toxin rather than a human hormone; the two behave similarly. Plecanatide has never been submitted for EU authorisation, so it is essentially a North American product.

2How it's thought to work

Guanylate cyclase-C (GC-C) sits on the surface of cells lining the intestine. When a guanylin-family peptide binds, the cell makes cyclic GMP, which opens the CFTR chloride channel; chloride and bicarbonate flow into the gut lumen and water follows, speeding transit and softening stool.

cGMP that leaks out of the cells reduces the firing of pain-sensing nerves in the gut wall, which is the proposed explanation for reduced abdominal pain in IBS-C (shown mainly for linaclotide in animal models).

Because it is pH-sensitive, plecanatide is thought to act mostly in the proximal small intestine and less in the colon, which was proposed as a reason for less diarrhoea than linaclotide; head-to-head data are lacking.

Essentially none reaches the bloodstream, so systemic effects are not expected.

The same receptor, modelled on the body's own uroguanylin instead of a bacterial toxin. It is more active where the gut is slightly acidic, which is proposed to localise the effect.Schematic — not to scale

3What the research shows

Chronic idiopathic constipation

Two 12-week, placebo-controlled Phase 3 trials (n=1,346 and n=1,337) reported that about 20–21% of patients on 3 mg were "durable overall complete spontaneous bowel movement responders" versus about 10–13% on placebo (Miner 2017, Am J Gastroenterol; DeMicco 2017, Therap Adv Gastroenterol). Effect sizes are modest and similar to linaclotide's. [2][3]

IBS with constipation

Two 12-week Phase 3 trials (combined n=2,189) reported overall responder rates (≥30% abdominal pain reduction plus an increase in complete spontaneous bowel movements in ≥6 of 12 weeks) of about 30% on 3 mg versus about 18% on placebo (Brenner 2018, Am J Gastroenterol). [4]

Graded B/D

Comparison with linaclotide

No head-to-head trial. Network meta-analyses find no clear difference in efficacy and suggest somewhat less diarrhoea with plecanatide, but confidence is low (Shah 2018, Am J Gastroenterol). [5]

Graded B (ongoing/unpublished)

Opioid-induced constipation, paediatric constipation

Paediatric functional constipation studies in children 6–17 were conducted after approval; results are not fully published †. Use under 6 is contraindicated.

Community / self-directed use

None documented.

4Reported side effects and interactions

Literature-reported

Diarrhoea is the main adverse effect (about 5% vs 1% placebo; severe diarrhoea in under 1%); if severe, the label advises stopping and rehydrating. Less common: abdominal distension, flatulence, abdominal tenderness, raised liver enzymes (rare), dizziness. Boxed warning: risk of serious dehydration in paediatric patients; contraindicated under 6 years because juvenile mice died from dehydration at human-equivalent doses (their GC-C receptors are more active in early life), and use in ages 6–17 is to be avoided outside studies. Contraindicated with known or suspected mechanical bowel obstruction.

Community-reported

none; no community use.

Theoretical. none of note; the drug is not systemically absorbed.

Interactions. none established; no CYP metabolism, no effect on absorption of other drugs documented. Additive loose stools with other laxatives or osmotic agents are the practical consideration.

Markers researchers commonly monitor

No compound-specific laboratory markers; monitoring is clinical:

Marker	Why it's watched
Stool frequency and consistency (Bristol scale) and complete spontaneous bowel movements per week	the trial endpoints and the practical measure of response.
Abdominal pain score (0–10 daily)	the second IBS-C endpoint.
Electrolytes (sodium, potassium) and hydration	only if diarrhoea is severe or prolonged; dehydration is the one serious label risk.
Weight and fluid intake in frail or elderly patients	same rationale.
Liver enzymes	rare rises reported; not routine.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Oral 3 mg tablet, once daily, with or without food. Keep in the original bottle with the desiccant; tablets are moisture-sensitive. For swallowing difficulty the label allows crushing in a teaspoon of applesauce or dispersing in 30 mL of water (drink, add 30 mL more, drink again), or giving via a nasogastric or gastric tube with water. Not injectable; the site calculator is not applicable.

6Commonly studied alongside

Linaclotide (same class, the usual comparator), lubiprostone, prucalopride, tenapanor and polyethylene glycol as alternative constipation treatments; fibre and osmotic laxatives as background. No peptide-community pairings; appears occasionally in discussions next to other gut peptides on this site such as BPC-157 (profile 1) and KPV, but with no shared mechanism or combined data.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved (Trulance) for CIC (January 2017) and IBS-C (January 2018) in adults; boxed warning for paediatric dehydration; label updated March 2024 (Salix)
European Union	Not authorised; no marketing application has been filed
United Kingdom	Not licensed
Australia	Not registered with the TGA
South Africa	Not registered with SAHPRA
Canada	Health Canada approved (Trulance) for CIC and IBS-C †
Sport	Not prohibited by WADA

8Open questions

Whether the proposed pH-selective action genuinely gives less diarrhoea than linaclotide — never tested head to head.
Long-term (>1 year) safety and whether the effect holds; extension studies were 52 weeks.
Paediatric use between 6 and 17, where trial data remain limited.

9References

1Shailubhai K et al. (2013). Plecanatide, an oral guanylate cyclase C agonist acting locally in the gastrointestinal tract, is safe and well-tolerated in single doses. Dig Dis Sci. PubMed · DOI
2Miner PB et al. (2017). A randomized phase III clinical trial of plecanatide, a uroguanylin analog, in patients with chronic idiopathic constipation. Am J Gastroenterol. PubMed · DOI
3DeMicco M et al. (2017). Randomized clinical trial: efficacy and safety of plecanatide in the treatment of chronic idiopathic constipation. Therap Adv Gastroenterol. PubMed · DOI
4Brenner DM et al. (2018). Efficacy, safety, and tolerability of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase 3 randomized clinical trials. Am J Gastroenterol. PubMed · DOI
5Shah ED et al. (2018). Efficacy and tolerability of guanylate cyclase-C agonists for irritable bowel syndrome with constipation and chronic idiopathic constipation: a systematic review and meta-analysis. Am J Gastroenterol. PubMed · DOI
6Trulance (plecanatide) US prescribing information (Salix, current). PubMed
7Health Canada. Summary Basis of Decision — Trulance. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

forum threads →

community protocols include this →

Threads and protocols are visible to members. Joining is free.

Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

30 Oct 2026Profile published — awaiting medical review

Licensed CC BY-NC-SA 4.0. Found an error? Report it · Editorial standards — corrections are logged here.