A 14-amino-acid peptide, related to the gut hormones guanylin and uroguanylin and to a toxin from diarrhea-causing E. coli bacteria, that works only inside the gut. It switches on guanylate cyclase-C in the gut lining, pulling fluid into the bowel to soften stool and speed it along; almost none reaches the blood.
Evidence. FDA-approved since 2012 as Linzess for IBS with constipation and chronic idiopathic constipation in adults; later US approvals added functional constipation from age 2 and IBS with constipation from age 7. In the EU and UK it is sold as Constella, for adults with IBS with constipation only. In the two main IBS-C trials, 34% met the FDA responder goal over 12 weeks vs 14–21% on placebo.
What it’s used for
Approved uses first, then uses tested in people, then claims that rest on animal studies or user reports.
IBS with constipation
LabelApproved for adults in the US, EU, UK, Canada, Australia and Japan. In two US trials, 34% met the FDA goal (less belly pain plus more complete bowel movements) vs 14–21% on placebo.
Chronic idiopathic constipation
LabelApproved for adults in the US, Canada, Australia and Japan, not the EU or UK. In two 12-week trials, 15–20% met the main bowel-movement goal vs 3–6% on placebo.
Bloating in IBS with constipation
LabelCovered by the IBS-C approval. In a 12-week trial of 614 adults, a combined bloating, discomfort and pain score fell 1.9 vs 1.2 points on placebo (0–10 scale).
Functional constipation in children
LabelUS-approved from age 2. Over 12 weeks, weekly bowel movements rose 2.6 vs 1.3 on placebo in 328 children aged 6–17, and 2.1 vs 1.4 in 123 aged 2–5. Children’s doses not shown.
IBS with constipation in children
LabelUS-approved from age 7 since November 2025, partly on adult evidence. In a 12-week trial without a placebo group, 30% of 53 children aged 7–17 met the pain and bowel-movement goal.
Opioid-induced constipation
TrialNot approved for this. In an 8-week phase 2 trial of 254 adults taking opioids for non-cancer pain, weekly bowel movements rose 2.9–3.5 vs 1.6 on placebo. No phase 3 result is published.
Bowel preparation for colonoscopy
TrialNot an approved use. A 2026 analysis of 8 trials (3,591 people), mostly from China, found that adding it to polyethylene glycol prep modestly improved bowel cleanliness.
Colorectal cancer prevention
TrialUnproven: in healthy volunteers, the approved capsules didn’t reliably activate their target in the colon lining, the researchers concluded. A phase 2 trial in people with colorectal tumors hasn’t reported results.
Label: an approved use. Trial: tested in people, with the result.
Approved in the US as Linzess capsules: since 2012 for IBS with constipation and chronic idiopathic constipation in adults, and since 2023–2026 for functional constipation from age 2 and IBS with constipation from age 7. A first generic, 72 mcg capsules, was approved on September 24, 2026.
Approval history
2012US FDA: Linzess: IBS with constipation and chronic idiopathic constipation in adults
2012EU (EMA): Constella: moderate to severe IBS with constipation in adults
2016Japan (PMDA): Linzess tablets: IBS with constipation; chronic constipation added in 2018
2023US FDA: Linzess: functional constipation in children aged 6–17
2025US FDA: Linzess: IBS with constipation in children 7 and older
2026US FDA: Linzess: functional constipation extended to children 2 and older
European Union
EMA-authorized since November 2012 as Constella, prescription only, for moderate to severe IBS with constipation in adults; not authorized for chronic constipation or under 18.
United Kingdom
Prescription-only medicine: Constella 290 mcg capsules for moderate to severe IBS with constipation in adults (UK SmPC revised June 2026).
Canada
Prescription drug: Constella capsules (72, 145, 290 mcg), approved December 2013, for IBS with constipation and chronic idiopathic constipation in adults and functional constipation at ages 6–17.
Australia
Prescription only (Schedule 4 since October 2019). Registered as Constella capsules (72, 145, 290 mcg) for adults with IBS with constipation or chronic idiopathic constipation.
Sport (WADA 2026)
Not banned in sportNot named on the 2026 list, and no section covers gut-acting guanylate cyclase-C agonists. S0 doesn’t apply to an approved drug.
Sport status follows the WADA Prohibited List in force since January 1, 2026; athletes should confirm with their anti-doping organization. Checked October 5, 2026. Status outside the US checked October 7, 2026 against EMA, MHRA, Health Canada and TGA records. By country: EU, UK, Canada, Australia. Status of every compound.
How it works
Linaclotide binds guanylate cyclase-C (GC-C), a receptor on the inner surface of the gut lining that the gut hormones guanylin and uroguanylin also use. This raises cGMP, a signaling molecule. Inside the cells, cGMP opens CFTR, a chloride channel, releasing chloride and bicarbonate so water follows into the bowel, softening stool and speeding transit; cGMP released outside the cells calmed pain-sensing nerves in animal studies. Linaclotide and its active metabolite act locally and are broken down in the gut, so almost none reaches the blood.
LabelBased on the product label.
Not known
How much of the pain relief in people comes from the nerve effect seen in animals is unknown, and where along the gut it mainly acts is still being studied. Controlled trials lasted 12–26 weeks; open-label use, up to 18 months.
Protocol
Label
Linzess, Constella
IBS with constipation: 290 mcg once daily, on an empty stomach at least 30 minutes before a meal. The EU and UK label (Constella) says to re-examine anyone not better after 4 weeks.
Label
Linzess
Chronic idiopathic constipation: 145 mcg once daily, or 72 mcg based on symptoms or tolerability.
Label
Linzess
Also approved in the US for IBS with constipation from age 7 and functional constipation from age 2; Vial Guide doesn’t show children’s doses.
Frequency
Once daily
Route
By mouth (capsule)
Timing
On an empty stomach, at least 30 minutes before a meal, at about the same time each day (label).
Cycle
Continuous. The labels treat it as ongoing therapy; the EU and UK label says to reassess anyone not improved after 4 weeks.
Week 15913172125
Continuous, shown over 26 weeks
Common protocols
The ways Linaclotide is most often run, each tagged with where it comes from.
IBS with constipation (adults)
Label
Dose
290 mcg
How often
Once daily, before a meal
How long
Ongoing; trials ran 12–26 weeks
Belly pain began easing in week 1, with the largest effect at weeks 6–9. The EU and UK label says to re-examine anyone not better after 4 weeks.
Chronic idiopathic constipation (adults)
Label
Dose
145 mcg, or 72 mcg
How often
Once daily, before a meal
How long
Ongoing; trials ran 12 weeks
72 mcg is an option based on symptoms or tolerability. 290 mcg did no better than 145 mcg for this use. Not an approved use in the EU or UK.
Opioid-induced constipation (phase 2)
Trial
Dose
145 or 290 mcg
How often
Once daily
How long
8 weeks
Not an approved use. In 254 adults taking opioids for chronic non-cancer pain, weekly bowel movements rose 2.9–3.5 vs 1.6 on placebo (Brenner 2020).
Taking it
Where it goes
Swallowed whole on an empty stomach, at least 30 minutes before a meal (label). If swallowing is hard, the capsule can be opened and the beads taken on a teaspoon of applesauce or in about 30 mL of water, or given through a feeding tube; the beads aren’t crushed or chewed.
If you miss a dose
Linzess label: skip the missed dose and take the next one at the regular time; don’t take 2 doses at once.
Bowel movements increase within the first week. In the IBS-C trials, belly pain began easing in week 1, with the largest effect at weeks 6–9.
Label
Weeks 1–2
Most diarrhea starts in this window. Severe diarrhea affected about 2% of adults on 145 or 290 mcg and under 1% on 72 mcg.
Label
Week 12
IBS-C: 34% met the combined goal (30% less belly pain plus at least 1 more complete bowel movement a week, in 6 of 12 weeks) vs 14–21% on placebo. Chronic constipation: about 1.5 more complete bowel movements a week than placebo.
Label
After stopping
When patients were switched to placebo, symptoms returned toward baseline within about a week, without rebound worsening.
Label
Side effects and what to do
Diarrhea (label: 20% vs 3% on placebo in IBS-C; 16% vs 5% on 145 mcg in chronic constipation)
Mostly starts in the first 2 weeks; 5% of IBS-C patients stopped because of it. The label says to stop dosing and rehydrate if it’s severe.
Belly pain (7% vs 5–6%), gas (4–6% vs 2–5%) and bloating (2–3% vs 1–2%) (label)
Usually mild. Severe or worsening belly pain, especially with bloody or black stools, needs prompt care.
Dehydration with severe diarrhea: dizziness, fainting, low blood pressure, low potassium or sodium (reported since approval)
Some cases needed hospital care or IV fluids. The UK label urges extra caution in older adults and people with heart disease, diabetes or high blood pressure.
Urgency or accidents (fecal incontinence), under 2% (label)
Taking it with food made stools looser in a study, so the label says to take it at least 30 minutes before a meal.
Allergic reactions: rash, hives, face or throat swelling, anaphylaxis (reported since approval)
Swelling of the face or throat or trouble breathing needs emergency care.
Stop and get medical help
Severe or ongoing diarrhea, dizziness or fainting, severe or worsening belly pain (especially with bloody or black stools), or swelling of the face or throat or trouble breathing. If a young child swallows a capsule, get help at once.
Can it cause …?
The side effects people ask about most, answered one by one. Each answer says where it comes from.
Tiredness
Not reportedTiredness isn’t listed in the US or UK labels, whose placebo-controlled trials gave it to over 2,000 adults for 12–26 weeks.
Headache
LabelHeadache: 4% vs 3% on placebo in the IBS-C trials; it wasn’t more common than placebo in the chronic constipation trials.
Nausea or vomiting
LabelNausea and vomiting are uncommon (under 1 in 100) in the UK label; vomiting was under 2% in US IBS-C trials, and nausea has been reported since approval.
Diarrhea or constipation
LabelDiarrhea: 20% vs 3% on placebo in IBS-C trials and 16–22% vs 5–7% in chronic constipation trials, mostly starting in the first 2 weeks; severe in about 2%.
Dizziness
LabelDizziness is common (1 to 10 in 100) in the UK label, and dizziness on standing uncommon. Severe diarrhea has caused fainting and low blood pressure needing hospital care.
Trouble sleeping
Not reportedTrouble sleeping isn’t listed in the labels, whose placebo-controlled trials gave it to over 2,000 adults for 12–26 weeks.
Hair loss
Not reportedHair loss isn’t listed in the labels, whose placebo-controlled trials gave it to over 2,000 adults for 12–26 weeks.
Acne, rash or skin changes
LabelRash, hives and serious allergic reactions, including throat swelling, have been reported since approval; hives are uncommon (under 1 in 100) in the UK label.
Water retention or swelling
LabelFluid retention isn’t listed. Angioedema, an allergic swelling of the face or throat, has been reported since approval and needs emergency care.
Joint or muscle pain
Not reportedNot listed in the labels’ trials (over 2,000 adults, up to 26 weeks). A 2025 analysis of US adverse-event reports found a muscle-spasm signal, which can’t prove cause.
Anxiety, low mood or irritability
Not reportedAnxiety or low mood isn’t listed in the labels, whose placebo-controlled trials gave it to over 2,000 adults for 12–26 weeks.
Low or high blood sugar
Not reportedBlood sugar changes aren’t listed, and almost none of the drug reaches the blood. In the UK label, people with diabetes reported diarrhea more often.
Fast heartbeat or blood pressure changes
LabelFast heartbeat isn’t listed. Low blood pressure, including dizziness on standing, has occurred with severe diarrhea and fluid loss (US and UK labels).
More hunger
LabelMore hunger isn’t listed; decreased appetite is listed as uncommon (under 1 in 100) in the UK label.
Liver strain
Not reportedLiver strain isn’t listed in the labels. Linaclotide is broken down in the gut, not by the liver, and liver disease needs no dose change.
Kidney problems
LabelKidney problems aren’t listed. Severe diarrhea has caused dehydration and low potassium or sodium needing IV fluids; kidney disease needs no dose change.
Cancer risk
LabelNo tumors in 2-year rat and mouse studies, and DNA-damage tests were negative. Its use to prevent colorectal cancer is being studied but unproven.
Label: from the prescribing information. Not reported: studied in people and not reported. A side effect that hasn’t been reported can still happen, especially with long or high-dose use. Any of these across every compound: the side-effect finder.
Who should avoid it
What its label rules out or warns about, most important first.
Children under 2
LabelRuled out (boxed warning). In newborn mice, a single dose at an adult-equivalent level caused deaths from dehydration, and data on the gut receptor in children under 2 are too limited to judge the risk.
Known or suspected bowel blockage
LabelRuled out by the US, EU and UK labels. Linaclotide draws fluid into the bowel and speeds transit.
Under-18s in the EU and UK
LabelThe EU and UK label says not to use it in children and teens, as safety and effectiveness weren’t established there. US approvals start at age 2.
Allergy to linaclotide
LabelRuled out in the EU and UK after hypersensitivity to it or any ingredient. Anaphylaxis and throat swelling have been reported in US use.
Crohn’s disease or ulcerative colitis
LabelNot studied, so the UK label doesn’t recommend it. It also reports rare bowel perforation in people whose bowel wall may be weakened.
Older adults or those prone to dehydration
LabelDiarrhea was more common in older, diabetic and high-blood-pressure patients. The UK label urges caution, and electrolyte checks, in people prone to fluid or salt imbalance.
Pregnancy
LabelBarely absorbed, so the US label doesn’t expect fetal exposure, but human data are limited. The EU and UK label prefers avoiding it in pregnancy as a precaution.
Interactions
Only interactions stated on a product label or measured in a human study are listed.
Birth-control pills
LabelSevere or prolonged diarrhea may reduce how well they’re absorbed. The EU and UK label recommends an extra method of contraception; no interaction study was done.
Laxatives, proton pump inhibitors (such as omeprazole) or NSAIDs (such as ibuprofen)
LabelThese may raise the risk of diarrhea, the EU and UK label says, and it advises caution when combining them.
Narrow-margin drugs absorbed in the gut (such as levothyroxine)
LabelTheir effect may drop if diarrhea is severe or prolonged. The EU and UK label advises caution; the US label notes no expected interactions through liver enzymes or drug transporters.
Label: a product label rules it out, warns about it or lists the interaction. This isn’t a complete list: a pharmacist or doctor can check a specific medicine or condition. Every documented interaction, by medicine: drug interactions.
Special situations
What the label and studies say about pregnancy, breastfeeding, kidney and liver problems, age and surgery.
Pregnancy
LabelBarely absorbed, so the US label doesn’t expect the fetus to be exposed; human data are too limited to judge risk. The EU and UK label prefers avoiding it in pregnancy as a precaution.
Breastfeeding
LabelNeither linaclotide nor its active metabolite was found in the milk of women taking it, so infant exposure isn’t expected. The UK label says it can be used while breastfeeding.
Kidney problems
LabelNo dose change: it’s broken down in the gut and not measurable in the blood, so kidney impairment isn’t expected to matter (US and UK labels). Severe diarrhea can still cause dehydration.
Liver problems
LabelNo dose change: it isn’t processed by the liver, so liver impairment isn’t expected to change its effect, per the US and UK labels.
Older adults
LabelOnly 7–11% of trial patients were 65 or older, too few to judge differences (US label). The UK label notes more diarrhea in older adults and advises careful monitoring and periodic reassessment.
Children and teens
LabelUS-approved for IBS with constipation from age 7 and functional constipation from age 2 (Canada: functional constipation at 6–17). Ruled out under 2. Not approved under 18 in the EU or UK.
Surgery and anesthesia
PrecautionNo label advice. It acts only inside the gut and isn’t measurable in the blood. Tell the surgical team about it, as about any regular medicine.
Label: what the prescribing information says. Precaution: not studied, so the caution follows from how it works or from a related drug. Ages are given as approved or studied; this site never gives doses for children. Across every compound: pregnancy, breastfeeding, kidney disease, liver disease, older adults and surgery.
Tracking and pairing
Worth tracking
Diarrhea and stool frequency in the first 2 weeks
Signs of dehydration: dizziness, fainting, very little urine
Potassium and sodium if diarrhea is severe or prolonged
Belly pain, or blood in the stool
Often paired with
Usually run on its own.
Human studies
5 key published human studies, with how many people took part. Animal studies aren’t listed here.
20111,276 people
The main bowel-movement goal was met by 21.2% and 16.0% on 145 mcg and 19.4% and 21.3% on 290 mcg vs 3.3% and 6.0% on placebo in chronic constipation; diarrhea led 4.2% to stop.
Design
Two randomized double-blind placebo-controlled phase 3 trials
Dose
145 or 290 mcg once daily
Length
12 weeks
Lembo et al., N Engl J Med 2011, PMID 21830967
2012804 people
33.7% vs 13.9% on placebo met the FDA responder goal for IBS with constipation (less belly pain plus more complete bowel movements); diarrhea led 4.5% vs 0.2% to stop.
Chey et al., Am J Gastroenterol 2012, PMID 22986437
2012800 people
33.6% vs 21.0% on placebo met the FDA responder goal in IBS with constipation; symptoms came back on switching to placebo, without worsening beyond baseline.
Design
Randomized double-blind placebo-controlled phase 3 trial with a 4-week randomized withdrawal
Dose
290 mcg once daily
Length
12 weeks, plus 4-week withdrawal
Rao et al., Am J Gastroenterol 2012, PMID 22986440
20181,223 people
The main bowel-movement goal was met by 13.4% on 72 mcg and 12.4% on 145 mcg vs 4.7% on placebo in chronic idiopathic constipation; diarrhea led 2.4% and 3.2% to stop.
Design
Randomized double-blind placebo-controlled trial
Dose
72 or 145 mcg once daily
Length
12 weeks
Schoenfeld et al., Am J Gastroenterol 2018, PMID 29091082
2021614 people
A combined bloating, discomfort and pain score (0–10) fell 1.9 vs 1.2 points on placebo in IBS with constipation; 40.5% vs 23.4% improved at least 2 points for 6 or more weeks.
Registered trials that are still running, or that finished without published results, most important first. Checked on ClinicalTrials.gov, October 7, 2026.
Phase 2NCT03796884
Linaclotide vs placebo for 7 days before colonoscopy or surgery in 150 people with colorectal adenomas or stage 0–3 colorectal cancer: whether it switches on its target (cGMP) in the tissue
Active, not recruiting; completion was estimated for September 2026, no results posted
Phase 1NCT05107219
A single dose of linaclotide or plecanatide, or no drug, before upper endoscopy in 43 adults: the cGMP signal in the duodenum, the first part of the small intestine
Completed February 2026; no results posted or published
Early phase 1NCT07569419
MRI crossover study in 26 healthy adults: where in the gut linaclotide draws in water, as groundwork for a trial in cystic fibrosis
Recruiting since March 2026; completion expected October 2026
Phase 4NCT03119584
Crossover trial of linaclotide vs placebo in 23 adults with type 2 diabetes and chronic constipation: bowel movement frequency
Active, not recruiting; completion expected January 2027
Phase 1/2NCT06692673
Pilot: linaclotide with a sports drink, instead of polyethylene glycol, as the only bowel prep before colonoscopy in 10 hospital patients
Listed as recruiting (last updated January 2026); completion was estimated for July 2026
Approval rests on placebo-controlled trials of 12–26 weeks in about 4,700 adults, mostly women, plus open-label studies of up to 18 months without a placebo group. Only 7–11% of trial patients were 65 or older. The US children’s approvals lean partly on adult data: the IBS-C trial in children compared two doses with no placebo group. Effects beyond 18 months are unknown, and uses outside the labels, such as bowel preparation, rest on smaller trials.
How it’s supplied
Capsules of 72, 145 or 290 mcg, swallowed whole; they can be opened and the beads taken on applesauce or in water. Taken by mouth, so there’s nothing to mix or draw up, and the calculator and dose log don’t apply.
Capsules in a bottle with a desiccant. Store at 25 °C (15–30 °C allowed), dry, tightly closed, in the original bottle; don’t remove the desiccant or repackage.
After mixing or opening
Nothing to mix. Beads from an opened capsule, on applesauce or in water, are taken at once, not stored. UK packs: use within 18 weeks of first opening, below 30 °C.
The drug is coated onto beads inside capsules (Japan uses tablets). The beads may be sprinkled on applesauce or into water but aren’t crushed or chewed. Strengths are in micrograms (72, 145 and 290 mcg), not milligrams.
Cautions
Boxed warning: not for children under 2. In newborn mice, a single dose at an adult-equivalent level caused deaths from dehydration. Accidental swallowing by a child can cause severe diarrhea.
Diarrhea is the most common side effect (16–22% of adults vs 3–7% on placebo), usually in the first 2 weeks, and severe in about 2%. The label says to stop dosing and rehydrate if it’s severe.
Severe diarrhea has caused fainting, low blood pressure and low potassium or sodium needing hospital care. The UK label urges extra caution in older adults and people with heart disease, diabetes or high blood pressure.
Not for anyone with a known or suspected bowel blockage. Severe or worsening belly pain, or bloody or black stools, need prompt care; the UK label lists rare bowel perforation.
Approved uses differ by country: the EU and UK allow it only for adults with IBS with constipation.
Questions
What is linaclotide?
A 14-amino-acid peptide, related to the gut hormones guanylin and uroguanylin and to a toxin from diarrhea-causing E. coli bacteria, that works only inside the gut. It switches on guanylate cyclase-C in the gut lining, pulling fluid into the bowel to soften stool and speed it along; almost none reaches the blood.
How does linaclotide work?
Linaclotide binds guanylate cyclase-C (GC-C), a receptor on the inner surface of the gut lining that the gut hormones guanylin and uroguanylin also use. This raises cGMP, a signaling molecule. Inside the cells, cGMP opens CFTR, a chloride channel, releasing chloride and bicarbonate so water follows into the bowel, softening stool and speeding transit; cGMP released outside the cells calmed pain-sensing nerves in animal studies. Linaclotide and its active metabolite act locally and are broken down in the gut, so almost none reaches the blood. How much of the pain relief in people comes from the nerve effect seen in animals is unknown, and where along the gut it mainly acts is still being studied. Controlled trials lasted 12–26 weeks; open-label use, up to 18 months.
Is linaclotide FDA-approved?
Approved in the US as Linzess capsules: since 2012 for IBS with constipation and chronic idiopathic constipation in adults, and since 2023–2026 for functional constipation from age 2 and IBS with constipation from age 7. A first generic, 72 mcg capsules, was approved on September 24, 2026.
What is the usual linaclotide dose?
From the label (Linzess, Constella): IBS with constipation: 290 mcg once daily, on an empty stomach at least 30 minutes before a meal. The EU and UK label (Constella) says to re-examine anyone not better after 4 weeks. Linzess: Chronic idiopathic constipation: 145 mcg once daily, or 72 mcg based on symptoms or tolerability. These are the amounts sources reference, not recommendations.
How is linaclotide taken?
By mouth: capsules of 72, 145 or 290 mcg, swallowed whole; they can be opened and the beads taken on applesauce or in water. On an empty stomach, at least 30 minutes before a meal, at about the same time each day (label). There’s nothing to mix or measure with a syringe.
Who should avoid linaclotide?
Children under 2: Ruled out (boxed warning). In newborn mice, a single dose at an adult-equivalent level caused deaths from dehydration, and data on the gut receptor in children under 2 are too limited to judge the risk. Known or suspected bowel blockage: Ruled out by the US, EU and UK labels. Linaclotide draws fluid into the bowel and speeds transit. Under-18s in the EU and UK: The EU and UK label says not to use it in children and teens, as safety and effectiveness weren’t established there. US approvals start at age 2. The “Who should avoid it” section lists 4 more groups and 3 interactions.
How should linaclotide be stored?
Before mixing: Capsules in a bottle with a desiccant. Store at 25 °C (15–30 °C allowed), dry, tightly closed, in the original bottle; don’t remove the desiccant or repackage. Nothing to mix. Beads from an opened capsule, on applesauce or in water, are taken at once, not stored. UK packs: use within 18 weeks of first opening, below 30 °C.
Is linaclotide banned in sport?
No. Not named on the 2026 list, and no section covers gut-acting guanylate cyclase-C agonists. S0 doesn’t apply to an approved drug.
Has linaclotide been studied in people?
Yes. The human studies section lists 5 published studies. The largest, from 2011, included 1,276 people. The main bowel-movement goal was met by 21.2% and 16.0% on 145 mcg and 19.4% and 21.3% on 290 mcg vs 3.3% and 6.0% on placebo in chronic constipation; diarrhea led 4.2% to stop.
How long has linaclotide been studied in people?
Label Open-label studies gave 290 mcg daily to 2,147 adults with IBS-C and 1,129 with chronic constipation for up to 18 months (US label).
Does linaclotide come in other forms, like a pill or nasal spray?
Label By mouth only: capsules (tablets in Japan) acting inside the gut; beads can go on applesauce, in water or via a feeding tube. Delayed-release versions eased pain in a phase 2b trial; none is approved.
Can you drink alcohol while taking linaclotide?
Precaution The labels don’t mention alcohol. Heavy drinking adds to fluid loss, which could worsen the dehydration that severe diarrhea on linaclotide can cause.
Can linaclotide be taken with semaglutide or tirzepatide?
No study No published study has combined them, and no label lists an interaction. Constipation is a common GLP-1 side effect, but linaclotide hasn’t been tested for it; both can cause diarrhea.
What happens if you take too much linaclotide?
Label In 22 healthy volunteers given single 2,897 mcg doses (10 times the top dose), diarrhea was the main effect (label). A child who swallows it may become severely dehydrated. Call Poison Help (1-800-222-1222), or emergency services for severe symptoms.
Sources
Linzess prescribing information, rev. 05/2026 (AbbVie and Ironwood, DailyMed)
Constella summary of product characteristics (EMA product information updated June 25, 2026; UK SmPC revised June 19, 2026)
Drugs@FDA: Linzess (NDA 202811) approval of August 30, 2012 and efficacy supplements of June 12, 2023, November 4, 2025 and May 21, 2026; linaclotide ANDA 211255 approved September 24, 2026
EMA: Constella (EMEA/H/C/002490), authorized November 26, 2012
PMDA list of new drug approvals: Linzess tablets, December 19, 2016 (IBS with constipation) and August 21, 2018 (chronic constipation)
Chey et al., 26-week trial of linaclotide in IBS with constipation (Am J Gastroenterol 2012) PMID 22986437
Lembo et al., two randomized trials of linaclotide for chronic constipation (NEJM 2011) PMID 21830967
Constella UK summary of product characteristics, sections 4.2, 4.4 and 4.8 (revised June 19, 2026)
Brenner et al., linaclotide for opioid-induced constipation, phase 2 (Pain 2020) PMID 32310620
Rao et al., 12-week IBS-C trial with randomized withdrawal (Am J Gastroenterol 2012) PMID 22986440
For how it works, who should avoid it and the limits of the evidence
Linzess prescribing information, boxed warning and sections 4, 5, 8, 12 and 14 (AbbVie and Ironwood, DailyMed, rev. 05/2026)
Constella UK summary of product characteristics, sections 4.2–4.6 and 4.8 (revised June 19, 2026), and EMA product information (updated June 25, 2026)
Bryant et al., linaclotide as a selective GC-C agonist acting locally in the gut (Life Sci 2010) PMID 20307554
Brancale et al., computational modeling of plecanatide and linaclotide, a synthetic analog of E. coli heat-stable enterotoxin (Pharmacol Res Perspect 2017) PMID 28357122
For uses, the side-effect questions, special situations, trials, identifiers and status outside the US
Linzess prescribing information, boxed warning and sections 1, 4, 5, 6, 8, 10, 12, 13 and 14 (AbbVie and Ironwood, DailyMed, rev. 05/2026)
Constella UK summary of product characteristics, sections 4.2, 4.4, 4.6, 4.8 and 4.9 (revised June 19, 2026); EMA product information and medicines data for Constella (updated 2026)
Drugs@FDA: Linzess (NDA 202811) supplements of June 12, 2023, November 4, 2025 and May 21, 2026; linaclotide ANDA 211255 approved September 24, 2026
Chang et al., phase 3b trial on bloating, discomfort and pain in IBS with constipation (Am J Gastroenterol 2021) PMID 34465695
Di Lorenzo et al., phase 3 trial in children aged 6–17 with functional constipation (Lancet Gastroenterol Hepatol 2024) PMID 38211604
Meine et al., meta-analysis of linaclotide added to polyethylene glycol bowel preparation (Surg Endosc 2026) PMID 41168471
Weinberg et al., bioactivity of oral linaclotide in the human colorectum for cancer prevention (Cancer Prev Res 2017) PMID 28396341
Chey et al., two delayed-release formulations of linaclotide in IBS with constipation, phase 2b (Am J Gastroenterol 2021) PMID 33065589
Fan et al., muscle spasms with linaclotide or plecanatide in FDA adverse-event reports (Front Pharmacol 2025) PMID 40843382
Andresen et al., first trial of linaclotide in women with IBS with constipation (Gastroenterology 2007) PMID 17854590
FDA Global Substance Registration System record for linaclotide (UNII, CAS, ATC, DrugBank and PubChem cross-references); KEGG D09355
Health Canada Drug Product Database and Constella product monograph (September 5, 2024); summary basis of decision (notice of compliance December 2, 2013)
Australian Poisons Standard, June 2026 instrument (linaclotide in Schedule 4), TGA scheduling decision in force from October 1, 2019, and ARTG entries 297703–297705
PMDA list of new drug approvals, April 2004 to February 2026 (Linzess tablets)
ClinicalTrials.gov registry entries for the trials listed (checked October 8, 2026)