Guanylate Cyclase-C (GC-C) AgonistPrescription OnlyPregnancy Cat. Linzess is contraindicated in pediatric patients up to 6 years of age. For patients 6 to 17 years, use should be avoided. In adults, based on animal data, linaclotide may cause fetal harm. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. No adequate and well-controlled studies exist in pregnant women.FDA
Linzess
linaclotide
Linzess (linaclotide) is a guanylate cyclase-C (GC-C) agonist indicated for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in adults. It works by binding to GC-C receptors on the luminal surface of intestinal epithelial cells, increasing intracellular cyclic guanosine monophosphate (cGMP), which accelerates intestinal fluid secretion and transit while reducing visceral pain. Linaclotide was approved by the FDA in August 2012, making it one of the first agents in its drug class to receive approval for both IBS-C and CIC indications. As a minimally absorbed peptide, it acts locally in the gastrointestinal tract with negligible systemic exposure, distinguishing it from many other gastrointestinal agents.
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Brand names:LinzessConstella
Quick Reference
Medicine ClassGuanylate Cyclase-C (GC-C) Agonist
FDA Approved
PregnancyCategory Linzess is contraindicated in pediatric patients up to 6 years of age. For patients 6 to 17 years, use should be avoided. In adults, based on animal data, linaclotide may cause fetal harm. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. No adequate and well-controlled studies exist in pregnant women.
FormsLinzess 72 mcg capsules, Linzess 145 mcg capsules
Quick Facts
- Active ingredient
- linaclotide
- Medicine class
- Guanylate Cyclase-C (GC-C) Agonist
- Brand names
- Linzess·Constella
- Availability
- Prescription only (Rx)
- Pregnancy category
- Linzess is contraindicated in pediatric patients up to 6 years of age. For patients 6 to 17 years, use should be avoided. In adults, based on animal data, linaclotide may cause fetal harm. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. No adequate and well-controlled studies exist in pregnant women.
- Treats
- Irritable Bowel Syndrome with Constipation (IBS-C)·Chronic Idiopathic Constipation (CIC)·Functional Constipation·Abdominal Pain associated with IBS·Chronic Constipation
- FDA approved
What Is Linzess?
Linzess (linaclotide) is a guanylate cyclase-C (GC-C) agonist indicated for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in adults. It works by binding to GC-C receptors on the luminal surface of intestinal epithelial cells, increasing intracellular cyclic guanosine monophosphate (cGMP), which accelerates intestinal fluid secretion and transit while reducing visceral pain. Linaclotide was approved by the FDA in August 2012, making it one of the first agents in its drug class to receive approval for both IBS-C and CIC indications. As a minimally absorbed peptide, it acts locally in the gastrointestinal tract with negligible systemic exposure, distinguishing it from many other gastrointestinal agents.
Linzess (linaclotide) belongs to the Guanylate Cyclase-C (GC-C) Agonist class of medications. It was first approved by the FDA in . This medication requires a prescription from a licensed healthcare provider.
Key Safety Information
- •Always follow the dose recommended by your healthcare professional. Taking more than prescribed increases the risk of side effects including serious complications.
- •Seek emergency care if you experience signs of an allergic reaction — hives, swelling, difficulty breathing, or rash. Stop the medication and call your doctor immediately.
- •Some medications can increase the risk of cardiovascular events. Tell your doctor if you have high blood pressure, a history of heart attack or stroke, or any pre-existing health condition.
- •Avoid or limit alcohol while taking Linzess. Do not drink alcohol without first discussing it with your healthcare provider as it may increase adverse effects.
- •Take Linzess with food or a full glass of water if stomach upset occurs. Stop use and talk to your doctor if you experience persistent stomach pain or GI symptoms.
- •Tell your doctor about all medications, supplements, and vitamins you take. Some combinations significantly increase the risk of harm.
This is a summary only. Always read the full prescribing information and consult your healthcare provider for personalized medical advice.
Uses & Indications
Linzess is prescribed for the following conditions. Some uses are FDA-approved indications; others may be evidence-based off-label uses. Consult your healthcare provider for personalized guidance.
Treatment of irritable bowel syndrome with constipation (IBS-C) in adults, including relief of abdominal pain, bloating, and infrequent or hard stools
Treatment of chronic idiopathic constipation (CIC) in adults when other measures have been insufficient
Relief of abdominal pain and discomfort associated with IBS-C, mediated through reduction of visceral hypersensitivity
Improvement of stool consistency and frequency in patients with IBS-C, including normalization of Bristol Stool Scale scores
Reduction of straining and incomplete evacuation sensation in CIC patients
Management of bloating and abdominal fullness in IBS-C through enhanced intestinal fluid secretion
Functional constipation management in patients who have failed dietary fiber supplementation and lifestyle modifications
Symptom control in patients with opioid-induced constipation when used off-label in clinical practice (not an approved indication)
Second-line therapy for constipation-predominant IBS in patients with inadequate response to dietary interventions
Management of chronic constipation in patients with comorbid conditions such as fibromyalgia or interstitial cystitis where IBS-C frequently co-occurs
Dosage Guide
The following are general dosing guidelines only. Your actual dose should be determined by your healthcare provider based on your condition, renal/hepatic function, and other medications.
AD
Adult Dosage
IBS-C: 290 mcg orally once daily, taken on an empty stomach at least 30 minutes before the first meal of the day. CIC: 72 mcg or 145 mcg orally once daily, taken on an empty stomach at least 30 minutes before the first meal of the day. The 145 mcg dose is typically the starting dose for CIC, with 72 mcg available for patients who experience excessive diarrhea. No dose adjustment is required for renal impairment or hepatic impairment as systemic absorption is negligible.
PD
Pediatric Dosage
Contraindicated in pediatric patients 6 years of age and younger due to risk of serious dehydration. Use should be avoided in patients 6 to 17 years of age. Safety and effectiveness have not been established in pediatric patients.
Available Forms
Linzess 72 mcg capsulesLinzess 145 mcg capsulesLinzess 290 mcg capsules
Available Strengths
Side Effects
Common
- Diarrhea (20% in IBS-C trials; 16% in CIC trials) — the most frequently reported adverse effect, often occurring within the first few weeks of therapy
- Abdominal pain (7%) — may occur or worsen transiently at treatment initiation
- Flatulence (4-6%) — increased gas production due to altered intestinal transit
- Abdominal distension (3-5%) — bloating sensation, particularly early in therapy
- Nausea (2-4%) — generally mild and transient
- Viral gastroenteritis (3%) — increased susceptibility reported in clinical trials
- Dyspepsia (2%) — upper abdominal discomfort or indigestion
Serious
- Severe diarrhea (Black Box Warning) — can lead to clinically significant dehydration, hypovolemia, and electrolyte imbalances, particularly dangerous in pediatric patients; discontinue immediately if severe diarrhea occurs
- Dehydration — especially in vulnerable populations including elderly patients and those with baseline fluid-electrolyte imbalances; monitor hydration status
- Electrolyte disturbances — hypokalemia, hyponatremia secondary to excessive fluid loss from severe diarrhea
- Hypovolemia — reduced blood volume from fluid losses can precipitate hypotension and tachycardia in severe cases
- Syncope or pre-syncope — reported in post-marketing experience, potentially related to dehydration and autonomic response
- Intestinal obstruction — while rare, discontinuation is warranted if mechanical obstruction is suspected or confirmed as linaclotide could exacerbate symptoms
- Rectal hemorrhage — uncommonly reported; evaluate for organic lower GI pathology if bleeding occurs
Rare
- Rectal hemorrhage — uncommon but reported in post-marketing surveillance
- Hematochezia — passage of fresh blood per rectum, requires clinical evaluation to rule out serious pathology
- Thyroid neoplasm (benign) — noted at high doses in long-term animal carcinogenicity studies; clinical relevance in humans at therapeutic doses is not established
- Allergic reactions — hypersensitivity including rash, urticaria, or angioedema, though rare given minimal systemic absorption
- Ischemic colitis — rare post-marketing case reports requiring prompt evaluation
- Collagenous colitis — isolated case reports in temporal association with linaclotide use
- Severe hypokalemia — in patients with baseline electrolyte vulnerabilities experiencing prolonged diarrhea
Medicine Interactions
Always inform your healthcare provider and pharmacist about ALL medications you take, including prescriptions, OTC medicines, vitamins, and supplements.
MajorModerateMinor
Warnings & Contraindications
⚠ Boxed Warning
BLACK BOX WARNING — Pediatric Risk: Linzess is contraindicated in patients 6 years of age and younger. Juvenile mice given linaclotide died from dehydration. Avoid use in patients 6 to 17 years of age. The safety and effectiveness have not been established in this age group.
Severe Diarrhea: Severe diarrhea has been reported. Patients requiring hospitalization for dehydration or electrolyte imbalance have been reported. If severe diarrhea occurs, suspend dosing and rehydrate the patient; reassess benefit-risk before resuming therapy.
Dehydration and Electrolyte Imbalance: Monitor patients at increased risk, including the elderly, patients with cardiac disease, renal impairment, or those taking diuretics for signs of dehydration and electrolyte abnormalities during treatment.
Mechanical Gastrointestinal Obstruction: Linzess is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Using a secretagogue in the presence of obstruction may cause bowel perforation or worsening obstruction.
Hypersensitivity Reactions: Discontinue Linzess and treat appropriately if signs or symptoms of a serious hypersensitivity reaction (anaphylaxis, angioedema) occur, although such reactions are rare given minimal systemic absorption.
Drug Interaction — Electrolyte-Active Medications: Particular caution is warranted when Linzess is used concurrently with medications that can cause hypokalemia or alter fluid balance, including loop diuretics, thiazides, and corticosteroids.
Post-Marketing Safety: Rectal hemorrhage and hematochezia have been reported; evaluate for organic colorectal pathology including colorectal malignancy before initiating therapy in appropriate patients.
Pregnancy Considerations: Animal studies at supratherapeutic doses suggest potential fetal harm. There are no adequate data in pregnant women. Use in pregnancy only if clearly needed and benefit outweighs risk; counsel patients accordingly.
Breastfeeding: It is not known whether linaclotide or its active metabolite is present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need and any potential adverse effects.
Long-Term Use: The safety of Linzess beyond 26 weeks has not been established in controlled trials. Periodically reassess the need for continued therapy and perform appropriate diagnostic evaluation if symptoms change significantly.
Renal and Hepatic Impairment: No formal dose adjustment studies were conducted. Given negligible systemic absorption, dose adjustment is not recommended, but patients should be monitored for GI adverse effects.
Concomitant Diarrhea-Promoting Medications: Avoid co-prescribing other secretagogues or laxatives without careful clinical justification, as additive diarrhea risk may increase the likelihood of dehydration.
How Linzess Works
Linaclotide is a 14-amino acid peptide that acts as a selective agonist at guanylate cyclase-C (GC-C) receptors located on the luminal surface of intestinal epithelial cells. Upon binding to GC-C, linaclotide stimulates the production of intracellular cyclic guanosine monophosphate (cGMP), which activates the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. Activation of CFTR promotes the secretion of chloride and bicarbonate ions into the intestinal lumen, driving osmotic water secretion, softening stool, and accelerating intestinal transit. Additionally, elevated intracellular and extracellular cGMP reduces the activity of visceral afferent pain fibers by inhibiting pain-signaling pathways, which accounts for the analgesic effect observed in IBS-C patients — an effect independent of and additive to its pro-secretory action.
Pharmacokinetics
Pregnancy & Breastfeeding Safety
Linzess is contraindicated in pediatric patients up to 6 years of age. For patients 6 to 17 years, use should be avoided. In adults, based on animal data, linaclotide may cause fetal harm. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. No adequate and well-controlled studies exist in pregnant women.
FDA Pregnancy Category Linzess is contraindicated in pediatric patients up to 6 years of age. For patients 6 to 17 years, use should be avoided. In adults, based on animal data, linaclotide may cause fetal harm. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. No adequate and well-controlled studies exist in pregnant women.
Consult your healthcare provider.
Full Pregnancy InformationBreastfeeding
Many medications pass into breast milk in varying amounts. Before using Linzesswhile breastfeeding, discuss the benefits and risks with your healthcare provider or pharmacist — they can weigh your dose, your infant's age, and available lactation safety data to find the safest option for you and your baby.
Storage & Handling
Store Linzess capsules at room temperature between 68°F to 77°F (20°C to 25°C). Excursions are permitted between 59°F to 86°F (15°C to 30°C). Keep the medication in the original bottle with the desiccant (silica gel packet) included — do not remove the desiccant from the bottle. Keep the bottle tightly closed. Protect from moisture and heat. Do not store in the bathroom medicine cabinet due to humidity exposure. Keep out of reach of children. Discard unused medication after the expiration date printed on the label.
Frequently Asked Questions
1
How long does it take for Linzess to start working?
Many patients begin to experience relief of constipation symptoms, including softer stools and more frequent bowel movements, within the first 1 to 3 days of starting Linzess. However, improvements in abdominal pain and bloating associated with IBS-C may take several weeks of consistent daily use to become fully apparent. Clinical trials demonstrated statistically significant improvements in both stool frequency and abdominal pain beginning in the first week of treatment. If you have not noticed any benefit after 4 weeks of regular use, discuss this with your healthcare provider.
2
Can I take Linzess with food?
No. Linzess should be taken on an empty stomach, at least 30 minutes before the first meal of the day. Taking it with food significantly increases the rate and severity of diarrhea. If you forget to take it before your meal, skip that dose entirely and take the next dose the following morning before eating. Do not take two doses at the same time to make up for a missed one.
3
What should I do if I experience severe diarrhea on Linzess?
Severe diarrhea is the most important adverse effect of Linzess. If you develop severe, persistent, or debilitating diarrhea, stop taking Linzess immediately and contact your healthcare provider. You should also ensure adequate fluid replacement to prevent dehydration. Warning signs that require prompt medical attention include dizziness, lightheadedness, extreme thirst, decreased urination, dry mouth, or muscle cramps — all of which may indicate dehydration or electrolyte imbalance. Seek emergency care if symptoms are severe.
4
Does Linzess interact with other medications?
Linzess has minimal systemic absorption, which limits many typical drug-drug interactions at the pharmacokinetic level. However, clinically important interactions exist. Concurrent use of diuretics, laxatives, or other diarrhea-promoting medications increases the risk of dehydration and electrolyte disturbances. Patients taking digoxin, lithium, or immunosuppressants should be monitored more closely if significant diarrhea develops, as fluid losses can alter the levels of these narrow-therapeutic-index drugs. Opioid pain medications can counteract Linzess's benefit by slowing bowel motility. Always inform your doctor and pharmacist about all medications, supplements, and herbal products you are taking.
5
Is Linzess safe during pregnancy?
The safety of Linzess during pregnancy has not been established in humans. Animal studies at doses higher than the human therapeutic dose suggest potential fetal harm. Linzess is not routinely recommended during pregnancy. If you are pregnant, planning to become pregnant, or become pregnant while taking Linzess, discuss this with your healthcare provider immediately. The decision to continue or discontinue therapy must weigh the potential benefit to the mother against the potential risk to the fetus.
6
Why is Linzess dangerous for children?
Linzess carries a Black Box Warning — the FDA's most serious safety alert — specifically regarding use in pediatric patients. Studies in juvenile mice showed that linaclotide caused rapid, severe dehydration and death when given at doses comparable to human therapeutic exposures scaled for body weight. Linzess is strictly contraindicated in children 6 years of age and younger, and its use should be avoided in patients 6 to 17 years old. If a child accidentally ingests Linzess, seek emergency medical attention immediately.
7
Can I open the Linzess capsule if I have trouble swallowing it?
Yes. If you have difficulty swallowing the capsule whole, you may carefully open it and sprinkle the beads inside into approximately 1 ounce (30 mL) of room-temperature water. Stir gently and swallow the mixture immediately — do not chew the beads. Do not store this mixture for later use. Alternatively, the beads can be mixed with 1 tablespoon of applesauce and swallowed immediately without chewing. Do not crush or chew the capsule or the beads.
8
What happens if I miss a dose of Linzess?
If you miss a dose of Linzess, skip the missed dose entirely and take your next scheduled dose the following morning before eating. Do not double up on doses to compensate for a missed one. Because Linzess is taken once daily and its effects are cumulative over days of consistent use, a single missed dose is unlikely to significantly impact your overall treatment. Consistency is important for best results, so try to take it at the same time each morning.
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Comprehensive Guide to Linzess
## What Is Linzess (Linaclotide)?
Linzess (linaclotide) is a prescription medication approved by the U.S. Food and Drug Administration (FDA) in August 2012 for the treatment of two distinct but related gastrointestinal conditions: irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in adults. It belongs to a drug class called guanylate cyclase-C (GC-C) agonists, making it one of the first medications of its kind.
Linzess works through a highly targeted mechanism that distinguishes it from traditional laxatives. It is a 14-amino acid peptide that acts as a selective agonist at guanylate cyclase-C (GC-C) receptors found on the surface of the cells lining the intestine. When linaclotide binds to these GC-C receptors, it triggers production of a molecule called cyclic guanosine monophosphate (cGMP). Rising cGMP levels inside intestinal cells activate the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. This channel pumps chloride and bicarbonate ions into the intestinal lumen, which draws water along with it through osmosis. The result is softer, more fluid stools and faster movement of intestinal contents.
Linzess is manufactured by AbbVie and Ironwood Pharmaceuticals. The standard recommended dose for IBS-C is 290 mcg once daily, and for CIC it is 145 mcg (or 72 mcg for dose-sensitive patients) once daily, always taken on an empty stomach at least 30 minutes before the first meal. The most important adverse effect is severe diarrhea, which carries a Black Box Warning regarding serious dehydration risk, especially in children. Linzess is contraindicated in patients 6 years of age and younger and should be avoided in patients 6 to 17 years old.
Sources & References
- • FDA Prescribing Information — Official labeling and package insert for Linzess
- • U.S. National Library of Medicine — MedlinePlus drug information
- • American Hospital Formulary Service (AHFS) — Clinical pharmacology monograph
- • PubMed / MEDLINE — View clinical studies
Last reviewed by MedCentralHub Medical Review Board · MedCentralHub Editorial Policy
Medical Disclaimer
The information on this page is for educational purposes only and is not intended as medical advice, diagnosis, or treatment. Always consult your doctor, pharmacist, or qualified healthcare provider before starting, stopping, or changing any medication.