linaclotide (Rx)

Brand and Other Names:Linzess
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Dosing & Uses


Dosage Forms & Strengths


  • 72mcg
  • 145mcg
  • 290mcg

Irritable Bowel Syndrome

Indicated for irritable bowel syndrome with constipation (IBS-C)

290 mcg PO qDay

Chronic Idiopathic Constipation

Indicated for chronic idiopathic constipation (CIC)

145 mcg PO qDay

72 mcg PO qDay may be used based on individual presentation

Dosage Modifications

Renal or hepatic impairment

  • Not expected to affect clearance of linaclotide or its active metabolite because linaclotide metabolism occurs within gastrointestinal tract and plasma concentrations are not measurable following administration of recommended dosage

<6 years: Contraindicated

6-17 years: Safety and efficacy not established (see Black Box Warnings and Cautions)

Irritable Bowel Syndrome

Not studied

Chronic Idiopathic Constipation

Use caution, selecting a dose should reflect the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy in this patient population


Adverse Effects



  • Diarrhea (20%)


  • Diarrhea (16-22%)



  • Abdominal pain (7%)
  • Flatulence (4%)
  • Headache (4%)
  • Viral gastroenteritis (3%)
  • Abdominal distension (2%)
  • Severe diarrhea (2%)
  • Defecation urgency (<2%)
  • Fecal incontinence (<2%)
  • Vomiting (<2%)
  • Gastroesophageal reflux disease (<2%)


  • Abdominal pain (7%)
  • Flatulence (6%)
  • Upper respiratory tract infection (5%)
  • Sinusitis (3%)
  • Abdominal distension (1-3%)
  • Defecation urgency (<2%)
  • Fecal incontinence (<2%)
  • Dyspepsia (<2%)
  • Viral gastroenteritis (<2%)

Postmarketing Reports

Hypersensitivity reactions: Anaphylaxis, angioedema, rash (including hives or urticaria)

Gastrointestinal reactions: Hematochezia, nausea, rectal hemorrhage



Risk of serious dehydration in pediatric patients

Contraindicated in patients aged <6 years; in neonatal mice, linaclotide caused deaths due to dehydration

Avoid use in patients aged 6 to <18 years

Safety and effectiveness have not been established in patients <18 years


Patients aged <6 years due to risk of serious dehydration

Known or suspected mechanical gastrointestinal obstruction


Pediatric risk

  • Contraindicated in patients <6 years of age
  • In neonatal mice, fluid secretion increased as a consequence of GC-C agonism resulting in mortality within the first 24 hr due to dehydration
  • Due to increased intestinal expression of GC-C, patients aged <6 years may be more likely than patients aged ≥6 years to develop severe diarrhea and its potentially serious consequences
  • Although there were no deaths in older juvenile mice, given deaths in young juvenile mice and lack of clinical safety and efficacy data in pediatric patients, avoid use of in pediatric patients 6 to <18 years


  • Diarrhea was the most common adverse reaction in clinical trials
  • In postmarketing reports, severe diarrhea associated with dizziness, syncope, hypotension and electrolyte abnormalities (hypokalemia and hyponatremia) requiring hospitalization or IV fluid administration have been reported
  • If severe diarrhea occurs, suspend dosing and rehydrate

Pregnancy & Lactation


Linaclotide and its active metabolite are negligibly absorbed systemically following oral administration, and maternal use is not expected to result in fetal exposure

Insufficient data available data on use in pregnant women to inform any drug-associated risk for major birth defects and miscarriage

Animal data

  • No effects on embryofetal 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


There is no information regarding the presence of linaclotide in human milk, or on its effects on milk production or the breastfed infant

No lactation studies in animals have been conducted

Unknown whether negligible systemic absorption of linaclotide by adults will result in a clinically relevant exposure to breastfed infants

Exposure to linaclotide in breastfed infants has the potential for serious adverse effects

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.



Mechanism of Action

Guanylate cyclase C (GC-C) agonist; activation of GC-C located on the luminal surface of intestinal epithelial cells leads to increased cyclic guanosine monophosphate (cGMP), anion secretion, fluid secretion, and intestinal transit

Appears to work topically rather than systemically; elevation in intracellular cGMP stimulates secretion of chloride and bicarbonate into the intestinal lumen, mainly through activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, resulting in increased intestinal fluid and accelerated transit


Minimal systemic absorption

Concentrations of linaclotide and its active metabolite in plasma are below the limit of quantitation after oral doses of 145 mcg or 290 mcg


Metabolized within the GI tract to its principal, active metabolite by loss of the terminal tyrosine moiety

Both linaclotide and the metabolite are proteolytically degraded within the intestinal lumen to smaller peptides and naturally occurring amino acids


Excretion: 3-5% feces (parent compound) and virtually 100% of active metabolite



Oral Administration

Take on an empty stomach at least 30 minutes before first meal of the day

Swallow capsule whole; do not chew or crush

Missed dose

  • Skip missed dose and take next dose at regular time; do not take 2 doses at the same time

Difficulty swallowing tablets

  • May sprinkle capsule contents on applesauce or in water; not tested in other soft foods or liquids
  • Administration in applesauce
    • Place 1 teaspoonful of applesauce at room temperature into a clean container
    • Open capsule
    • Sprinkle entire contents (beads) on applesauce
    • Consume entire contents immediately; do not chew beads; do not store applesauce-beads mixture for later use
  • Administration in water
    • Pour ~1 ounce (30 mL) of bottled water at room-temperature into clean cup
    • Open capsule
    • Sprinkle entire contents (beads) into water
    • Gently swirl beads and water for at least 20 sec
    • Swallow entire mixture of beads and water immediately
    • Add another 30 mL of water to any beads remaining in cup, swirl for 20 seconds, and swallow immediately
    • Do not store the bead-water mixture for later use
    • Note: Drug is coated on surface of the beads and will dissolve off the beads into water; beads will remain visible and will not dissolve; therefore, it is not necessary to consume all beads to deliver complete dose
  • Nasogastric or gastric feeding tube administration in water
    • Open capsule and empty the beads into clean container with 1 ounce (30 mL) of room-temperature bottled water
    • Mix by gently swirling beads for at least 20 sec
    • Draw-up beads and water mixture to an appropriately sized catheter-tipped syringe and apply rapid and steady pressure (10 mL/10 sec) to dispense syringe contents into the tube
    • After administering the bead-water mixture, flush nasogastric/gastric tube with a minimum of 10 mL of water
    • Note: It is not necessary to flush all the beads through to deliver complete dose


Store at 25ºC (77ºF); excursions permitted between 15-30ºC (59-86ºF)

Keep in the original container; do not subdivide or repackage

Protect from moisture

Do not remove desiccant from the container





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Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.