Supplied as capsules or tablets

Gut & Gastrointestinal

At a glance

Ten answers, each one line. Open any row for the detail behind it.

What it does Proof that an oral peptide drug can work well — by not being absorbed at all.

Proof that an oral peptide drug can work well — by not being absorbed at all. Linaclotide acts entirely on the luminal surface of the gut and is essentially undetectable in blood, which sidesteps the systemic side effects that limit most peptides.

How it works in detail

Half-life Minimally absorbed — acts locally in the gut lumen — Documented

Minimally absorbed — acts locally in the gut lumen

Typical studied dose Set on the approved label, which states the starting dose, how it is… — On the label

Set on the approved label, which states the starting dose, how it is increased and the maximum. Read it there rather than anywhere else — including here.

Read the prescribing information

How often it is used The label schedule is once daily. Dosing intervals follow the half-life… — On the label

The label schedule is once daily. Dosing intervals follow the half-life above, and the prescribing information is what sets them.

How it is taken Oral capsule, once daily — Documented

Oral capsule, once daily

Main side effects Boxed warning: contraindicated in young children · Severe diarrhea and dehydration · Contraindicated in mechanical obstruction — Carries serious risk

Boxed warning: contraindicated in young children — Contraindicated under 2 years of age due to fatal dehydration in juvenile animal studies. This is an absolute contraindication, not a caution.

Severe diarrhea and dehydration — Can be serious in the elderly or in anyone unable to maintain fluid intake; the drug should be stopped.

Contraindicated in mechanical obstruction — Increasing intestinal secretion behind an obstruction is dangerous.

All benefits and risks, weighed

Storage before mixing Kept dry, sealed and at room temperature unless the label says…

Kept dry, sealed and at room temperature unless the label says otherwise. Moisture is what shortens the life of a capsule or tablet.

Shelf life after mixing Nothing to mix — it is not supplied as a powder. The relevant date is…

Nothing to mix — it is not supplied as a powder. The relevant date is the one printed on the product.

Evidence level 5/5 · Very strong — Documented

Multiple phase 3 randomized trials plus regulatory approval in a major market.

How we rate evidence · What the studies found

Regulatory status FDA Approved — Documented

FDA-approved for irritable bowel syndrome with constipation and for chronic idiopathic constipation, including a pediatric indication. Prescription drug.

Read the prescribing information · The full legal position

Overview

FDA ApprovedFDA-approved for irritable bowel syndrome with constipation and for chronic idiopathic constipation, including a pediatric indication.

At a glance

Regulatory status	FDA-approved for irritable bowel syndrome with constipation and for chronic idiopathic constipation, including a pediatric indication.
Drug class	Guanylate cyclase-C agonist — 14-amino-acid peptide with three disulfide bridges
Route	Oral capsule, once daily
Half-life	Minimally absorbed — acts locally in the gut lumen
Evidence rating	5/5 Very strong Evidence rating 5 out of 5: Very strong Multiple phase 3 randomized trials plus regulatory approval in a major market.
Studied in	Multiple phase 3 trials in IBS-C and chronic idiopathic constipation; a dedicated pediatric functional constipation program.

Linaclotide sequence & structure

Linaclotide is a 14-residue disulfide-bridged peptide with a free C-terminal acid; molecular weight 1,526.8 Da.

Amino acid sequence (N-terminus → C-terminus)

H-CCEYCCNPACTGCY-OH

Three-letter	`H-Cys-Cys-Glu-Tyr-Cys-Cys-Asn-Pro-Ala-Cys-Thr-Gly-Cys-Tyr-OH`
Length	14 amino acid residues
Modifications	Disulfide bond — Cys1–Cys6 Disulfide bond — Cys2–Cys10 Disulfide bond — Cys5–Cys13
Molecular formula	C₅₉H₇₉N₁₅O₂₁S₆
Molecular weight	1,526.8 Da (average, free base)
SMILES	`C[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(N)=O)NC(=O)[C@@H]2CSSC[C@H](N)C(=O)N[C@H]3CSSC[C@H](NC1=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)CSSC[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC3=O)C(=O)N2`
Identifiers	CAS 851199-59-2 · PubChem CID 16158208 · DrugBank DB08890
Sources	DailyMed — LINZESS (linaclotide) capsules label, section 11 Description ChEMBL CHEMBL3301675 (HELM notation with disulfide map 1–6, 2–10, 5–13; MW 1526.77)PubChem CID 16158208 (formula C59H79N15O21S6, MW 1526.8, SMILES)PubChem CID 16158208 synonyms (CAS 851199-59-2, UNII N0TXR0XR5X, DB08890, CHEMBL3301675)KEGG DRUG D09355 Linaclotide (JAN/USAN) — sequence with disulfides 1-6, 2-10, 5-13; formula; MW 1526.75; CAS 851199-59-2

All 14 residues are L-amino acids with a free N-terminal amine and C-terminal acid; the three disulfides (1–6, 2–10, 5–13) form a knotted heat-stable-enterotoxin-like fold that is essential for GC-C binding, so vendor material with mis-paired disulfides is inactive. Linzess/Constella is formulated as the free peptide (no salt); average MW is 1526.8 (PubChem/FDA label; KEGG 1526.75, ChEMBL 1526.77). Its active metabolite MM-419447 is the 13-residue des-Tyr14 peptide.

Record confidence: high — two independent authoritative sources agree on the sequence and modifications. Every sequence on the site is listed with its sources on the peptide sequences index.

How it works

Agonises guanylate cyclase-C on the luminal surface of intestinal epithelium, raising intracellular and extracellular cyclic GMP. That increases chloride and bicarbonate secretion, drawing fluid into the lumen and accelerating transit. Extracellular cGMP also reduces visceral afferent nociceptor firing, which explains the pain benefit that laxatives do not provide.

Evidence base

Rated 5 of 5 — Very strong. Multiple phase 3 randomized trials plus regulatory approval in a major market.

Multiple replicated phase 3 trials with patient-reported endpoints agreed with regulators in advance.

Benefits and risks, weighed against the evidence

Every entry below carries the strength of the evidence behind it — three bars for strong human data, two for moderate, one for preliminary or preclinical work. The two columns are not equal by design: where a compound has more documented risk than demonstrated benefit, the lists say so.

Reported benefits

4 entries · 4 on strong human evidence

Relieves both constipation and abdominal pain

The visceral analgesic effect is mechanistically distinct from the laxative effect, and is what separates it from osmotic laxatives.
Evidence: Strong evidence
Essentially no systemic exposure

Plasma concentrations are generally below the limit of quantification, which largely removes systemic drug interactions.
Evidence: Strong evidence
Consistent phase 3 results

Replicated across multiple trials in both indications with validated symptom endpoints.
Evidence: Strong evidence
Pediatric indication

Approved for functional constipation in children within a defined age range, supported by its own trial.
Evidence: Strong evidence

Risks and cautions

5 entries · 3 serious or common

Boxed warning: contraindicated in young children

Contraindicated under 2 years of age due to fatal dehydration in juvenile animal studies. This is an absolute contraindication, not a caution.
Evidence: Serious
Diarrhea

The most common adverse effect and the main reason for discontinuation — an on-target consequence of the mechanism.
Evidence: Moderate evidence
Severe diarrhea and dehydration

Can be serious in the elderly or in anyone unable to maintain fluid intake; the drug should be stopped.
Evidence: Serious
Contraindicated in mechanical obstruction

Increasing intestinal secretion behind an obstruction is dangerous.
Evidence: Serious
Abdominal pain, bloating and flatulence

Common early in treatment.
Evidence: Minor

Counts are not a score. A single serious risk can outweigh several well-supported benefits, and a long benefit list built on preclinical work outweighs nothing at all.

Opinion — what people actually report

5 themes · 2 reported benefits · 1 reported problem

This is the weakest tier on this site. These are themes drawn from public discussion — forums, subreddits and patient threads — not from trials. There is no control group, no denominator, and no way to confirm that what someone injected matched its label. People post when a result is dramatic and when something goes wrong, and rarely when nothing happens, so treat everything below as a description of the conversation rather than of the compound. The bars count how often a thing is said, not how well it is supported.

Diarrhoea is the reason people stop Reported problem. Dominant theme: Comes up in most discussions of this compound.

The dominant theme by a wide margin, frequently described as going from one extreme to the other and as urgent enough to affect work.
Timing before food is treated as essential Practical note. Dominant theme: Comes up in most discussions of this compound.

Taking it well before the first meal is the near-universal community advice for managing the diarrhoea, and it matches the labelling.
Works when nothing else did Reported benefit. Recurring: Raised regularly, though not by everyone.

Strongly positive reports from people who had exhausted fibre, osmotic laxatives and dietary approaches.
Abdominal pain improving, not just constipation Reported benefit. Recurring: Raised regularly, though not by everyone.

Reported as a distinct benefit and one people did not expect.
Dose reduction is common Practical note. Recurring: Raised regularly, though not by everyone.

Many describe opening capsules or moving to a lower strength, though the first of those is not a labelled practice.

Where the reports and the evidence part ways

Reports match the trials well: diarrhoea is the most common adverse event and the leading cause of discontinuation in the registration programme, and the pain benefit is a genuine trial finding rather than a bonus effect, since linaclotide reduces visceral hypersensitivity as well as accelerating transit. The one thing the community handles less carefully than the evidence does is the paediatric contraindication — this is contraindicated in young children because of a fatal dehydration signal in juvenile animals, and that is a hard boundary rather than a cautious default.

Questions & answers

Readers on Linaclotide

Questions and answers from readers, under generated names. Nothing here has been checked or reviewed by the site and none of it is medical advice. It is the least verified thing on this page — and it is here because people ask each other these things anyway, and most of the other places they can ask are run by sellers.

0 questions · 0 answers

Other readers answer these. Ask about Linaclotide and the people who have actually looked into it can reply. You post under a generated name — two ordinary words — and that is the only thing anyone else sees. Your address is never shown on the page, never sold and never used for marketing. What we keep, and why.

No questions yet. Ask the first one above — it takes one box and an email address.

How names work, and the house rules

Names. Every verified address is given one generated name — two ordinary words — and keeps it. Nobody chooses a name and nobody can take another's. Posts marked desk were written by the site's own editorial desk, usually to open a thread; they carry a generated name like everyone else's and are held to the site's rules, which means they never state an amount.

What is not allowed. Selling, sourcing, vendor names, coupon codes and "message me" — posts that read that way are held and usually removed. Personal medical details you would not want public. Abuse. Instructions framed as what someone else should do.

What this is not. A reader's report of what happened to them is a report, not a finding, and an answer here is one person's view. Nothing in this section changes the evidence rating above it. If something you read here would change what you take, take it to a pharmacist or physician first.

Your data. Delete any post of yours at any time, or remove everything you have written together with your name. Details in the privacy notice.

Who should avoid it

Children under 2 years — boxed warning
Known or suspected mechanical gastrointestinal obstruction
Severe dehydration

If used under medical supervision, monitor

Stool frequency and consistency
Hydration status, particularly in elderly patients
Symptom response at 4–12 weeks

Interactions

Not exhaustive. Always have a pharmacist or physician review your full medication list — including supplements.

Minimal — negligible systemic absorption means essentially no pharmacokinetic drug interactions
Other laxatives — additive diarrhea risk

Commonly confused with

These mix-ups cause real harm — two products sold under one name, or two molecules whose effects run in opposite directions.

Plecanatide FDA Approved Evidence 4/5

Same target and same indications. Plecanatide is modelled on uroguanylin and is pH-sensitive, which is claimed to concentrate activity in the small intestine and reduce diarrhea rates.

Compare side by side

Regulatory & legal status

Prescription drug.

Infographic

Linaclotide — benefits & risks at a glance Download SVG

Where to read further

We link to live literature searches rather than a frozen citation list, so you always see current results — including anything published after our last review.

IBSconstipationoral peptideapprovedgut

Related peptides in Gut & Gastrointestinal

Terms used on this page

Oral Peptide Delivery: Oral peptide delivery is the formulation of a peptide into a swallowed dosage form, a route that fights gastric acid, gut proteases and an epithelium built to exclude large molecules.
Adverse Drug Reaction (ADR): An adverse drug reaction is a noxious, unintended response to a medicine given at normal doses, and unlike an adverse event the term carries a causal judgement inside it.
Good Manufacturing Practice (GMP): Good manufacturing practice is the enforceable quality system governing how a drug is made, requiring qualified facilities, validated processes and documented control of every batch.
Phase 3 Trial: A Phase 3 trial is the large confirmatory study, powered for a prespecified clinical endpoint, on which a marketing application and the resulting product label are built.
Drug-Drug Interaction (DDI): A drug-drug interaction is a change in one medicine's exposure or effect caused by another, arising pharmacokinetically through absorption or metabolism, or pharmacodynamically at the effect site.
Contraindication vs Precaution: A contraindication marks a situation where a drug must not be used at all, while a precaution flags a risk that calls for caution, monitoring or a modified plan rather than avoidance.

This page is educational information, not medical advice. It cannot account for your medical history, medications, or risk factors. Do not start, stop or change any treatment based on it. Speak to a qualified healthcare professional who knows your case.