Linaclotide

Linaclotide is structurally related to human guanylin and uroguanylin and functions as a guanylate cyclase-C (GC-C) agonist. Both linaclotide and its active metabolite bind to GC-C and act locally on the luminal surface of the intestinal epithelium.

• LINZESS is indicated for the treatment of: • irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older • chronic idiopathic constipation (CIC) in adults • functional constipation (FC) in pediatric patients 2 years of age and older LINZESS is a guanylate cyclase-C agonist indicated for treatment of: Irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older. ( 1 ) Chronic idiopathic constipation (CIC) in adults.ICD-10: K58.9, K59.00

• LINZESS is contraindicated in: Patients less than 2 years of age due to the risk of serious dehydration [see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.4 )] . Patients with known or suspected mechanical gastrointestinal obstruction.contraindicated

The recommended dosage in adults is: IBS-C : 290 mcg orally once daily. ( 2.1 ) CIC : 145 mcg orally once daily or 72 mcg orally once daily based on individual presentation or tolerability. ( 2.1 ) The recommended dosage in pediatric patients: 7 years of age and older with IBS-C : 145 mcg orally once daily. ( 2.1 ) 2 years of age and older with FC : 72 mcg orally once daily. ( 2.1 ) Administration Instructions ( 2.2 ): Take on empty stomach at least 30 minutes prior to a meal at approximately the same time each day. Do not crush or chew LINZESS capsule or capsule contents. For patients who have difficulty swallowing capsules whole or those with a nasogastric or gastrostomy tube, see full prescribing information for instructions for opening the capsule and administering with applesauce or water. 2.1 Recommended Dosage Irritable Bowel Syndrome with Constipation (IBS-C) : The recommended dosage of LINZESS is: • Adults : 290 mcg orally once daily • Pediatric patients 7 years of age and older : 145 mcg orally once daily Chronic Idiopathic Constipation (CIC) in Adults The recommended dosage of LINZESS in adults is 145 mcg orally once daily. A dosage of 72 mcg once daily may be used based on individual presentation or tolerability. Functional Constipation (FC) in Pediatric Patients 2 Years of Age and Older The recommended dosage of LINZESS in pediatric patients 2 years of age and older is 72 mcg orally once daily. 2.2 Preparation and Administration Instructions • Take LINZESS on an empty stomach, at least 30 minutes prior to a meal at approximately the same time each day.

Diarrhea: Patients may experience severe diarrhea. If severe diarrhea occurs, suspend dosing and rehydrate the patient. ( 5.2 ) 5.1 Risk of Serious Dehydration in Pediatric Patients Less Than 2 Years of Age LINZESS is contraindicated in patients less than 2 years of age. In neonatal mice (human age equivalent of approximately 0 to 28 days), linaclotide increased fluid secretion as a consequence of age-dependent elevated GC-C agonism which was associated with increased mortality within the first 24 hours due to dehydration. There was no age-dependent trend in GC-C intestinal expression in a clinical study of children 2 to less than 18 years of age; however, there are insufficient data available on GC-C intestinal expression in children less than 2 years of age to assess the risk of developing diarrhea and its potentially serious consequences in these patients [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.4 ) ] . 5. 2 Diarrhea In adults, diarrhea was the most common adverse reaction of LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar between the IBS-C and CIC populations. Severe diarrhea was reported in 2% of adult patients with IBS-C or CIC treated with LINZESS 145 mcg or 290 mcg once daily, and in <1% of adult patients with CIC treated with LINZESS 72 mcg once daily [see Adverse Reactions ( 6.1 )] .

Most common adverse reactions (≥2%) reported in adult patients with IBS-C or CIC are: diarrhea, abdominal pain, flatulence and abdominal distension. ( 6.1 ) Most common adverse reaction (≥2%) reported in pediatric patients 7 to 17 years of age with IBS-C and 6 to 17 years of age with FC is diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie, Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Demographic characteristics were comparable between treatment groups in all studies [see Clinical Studies ( 14.1 , 14.2 , 14.3 , 14.4 , 14.5 )] . Irritable Bowel Syndrome with Constipation (IBS-C) in Adults Most Common Adverse Reactions The data described below reflect exposure to LINZESS in the two placebo-controlled clinical trials involving 1605 adult patients with IBS-C (Trials 1 and 2) [see Clinical Studies ( 14.1 )] . Patients were randomized to receive placebo or 290 mcg LINZESS once daily on an empty stomach for up to 26 weeks. Table 1 provides the incidence of adverse reactions reported in at least 2% of IBS-C patients in the LINZESS treatment group and at an incidence that was greater than in the placebo group.

8. 1 Pregnancy Risk Summary Linaclotide and its active metabolite are negligibly absorbed systemically following oral administration [see Clinical Pharmacology ( 12.3 )] , and maternal use is not expected to result in fetal exposure to the drug. The available data on LINZESS use in pregnant women are not sufficient to inform any drug-associated risk for major birth defects and miscarriage. In animal developmental studies, no effects on embryo-fetal development were observed with oral administration of linaclotide in rats and rabbits during organogenesis at doses much higher than the maximum recommended human dosage. Severe maternal toxicity associated with effects on fetal morphology were observed in mice ( see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data The potential for linaclotide to cause harm to embryo-fetal development was studied in rats, rabbits and mice.

Metabolism

Absorption LINZESS is minimally absorbed with negligible systemic availability following oral administration. Concentrations of linaclotide and its active metabolite in plasma are below the limit of quantitation after oral doses of 72 mcg, 145 mcg, or 290 mcg were administered.

Single LINZESS doses of 2897 mcg were administered to 22 healthy subjects; the safety profile in these subjects was consistent with that in the overall LINZESS-treated population, with diarrhea being the most commonly reported adverse reaction.

• Aug 30, 2012NDANDA202811Abbvie

1. 1Diarrhoea4,58018%
2. 2Drug Ineffective4,43017%
3. 3Off Label Use3,27913%
4. 4Constipation1,9377.5%
5. 5Nausea1,4145.5%
6. 6Fatigue1,1434.4%
7. 7Abdominal Distension1,1344.4%
8. 8Abdominal Pain1,0414.1%
9. 9Headache1,0073.9%
10. 10Pain9283.6%
11. 11Abdominal Pain Upper9083.5%
12. 12Dizziness8183.2%
13. 13Inappropriate Schedule Of Product Administration7392.9%
14. 14Flatulence6882.7%
15. 15Fall6792.6%

The 10 most recently updated of 59 ClinicalTrials.gov registrations naming Linaclotide as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Assess Adverse Events and Change in Symptoms With Linaclotide Versus Placebo in Pediatric Subjects, Ages 2 to 5 Years, With Functional Constipation
  Completed · Phase 3 · Interventional · 123 enrolled · AbbVie
  NCT05652205updated 2026-05-14
• Proof of Principle Study for an Efficacy Trial of Linaclotide for Cystic Fibrosis
  Recruiting · Early phase 1 · Interventional · 26 enrolled · University of Nottingham
  NCT07569419updated 2026-05-06
• GCC Agonist Signal in the Small Intestine
  Completed · Phase 1 · Interventional · 43 enrolled · University of Wisconsin, Madison
  NCT05107219updated 2026-04-07
• Efficacy of Linaclotide in Type II Diabetics With Chronic Constipation
  Active not recruiting · Phase 4 · Interventional · 23 enrolled · Texas Tech University Health Sciences Center, El Paso
  NCT03119584updated 2026-04-03
• Linaclotide in Treating Patients With Stages 0-3 Colorectal Cancer
  Active not recruiting · Phase 2 · Interventional · 230 enrolled · Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
  NCT03796884updated 2026-04-02
• "Efficacy and Safety of Linaclotide in Chronic Constipation"
  Not yet recruiting · Phase 4 · Interventional · 90 enrolled · Md Mehedi Shahriar
  NCT07431957updated 2026-02-25
• Linaclotide for Colonoscopy Bowel Prep
  Recruiting · Phase 1 · Phase 2 · Interventional · 10 enrolled · University of Florida
  NCT06692673updated 2026-01-23
• A Study of Virtual Reality and Linaclotide for IBS-C
  Recruiting · Interventional · 65 enrolled · Mayo Clinic
  NCT05796388updated 2026-01-20
• A Study to Assess Adverse Events and Change in Disease Activity in Pediatric Participants (Age 6 Months to <2 Years) With Functional Constipation Who Are Treated With Linaclotide
  Completed · Phase 2 · Interventional · 19 enrolled · AbbVie
  NCT05760313updated 2026-01-06
• Long-term Safety of Linaclotide in Pediatric Participants With FC or IBS-C
  Completed · Phase 3 · Interventional · 381 enrolled · AbbVie
  NCT04166058updated 2026-01-06

Frequently asked questions

How does Linaclotide work?

Linaclotide is structurally related to human guanylin and uroguanylin and functions as a guanylate cyclase-C (GC-C) agonist. Both linaclotide and its active metabolite bind to GC-C and act locally on the luminal surface of the intestinal epithelium.

What is Linaclotide used for?

According to FDA labeling, Linaclotide carries indications including: LINZESS is indicated for the treatment of: • irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older • chronic idiopathic constipation (CIC) in adults • functional constipation (FC) in pediatric patients 2 years of age and older LINZESS is a guanylate cyclase-C agonist indicated for treatment of: Irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older. ( 1 ) Chronic idiopathic constipation (CIC) in adults.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Linaclotide?

Linaclotide is classified as Other drugs for constipation, Guanylate Cyclase-C Agonist, Chloride Channel Activators, Guanylate Cyclase Activators, Increased Gastric Motility, Stimulation Large Intestine Fluid/Electrolyte Secretion, Stimulation Small Intestine Fluid/Electrolyte Secretion.

What are the brand names for Linaclotide?

Linaclotide is marketed under brand names including Linzess.

What are the contraindications for Linaclotide?

Linaclotide labeling lists contraindications including: LINZESS is contraindicated in: Patients less than 2 years of age due to the risk of serious dehydration [see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.4 )] . Patients with known or suspected mechanical gastrointestinal obstruction.. Always consult the full prescribing information and a clinician.