Skip to Content

Linaclotide

Pronunciation

(lin AK loe tide)

Index Terms

  • Linaclotide Acetate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Linzess: 72 mcg, 145 mcg, 290 mcg

Brand Names: U.S.

  • Linzess

Pharmacologic Category

  • Gastrointestinal Agent, Miscellaneous
  • Guanylate Cyclase-C (GC-C) Agonist

Pharmacology

Linaclotide and its active metabolite bind and agonize guanylate cyclase-C on the luminal surface of intestinal epithelium. Intracellular and extracellular cyclic guanosine monophosphate (cGMP) concentrations are subsequently increased resulting in chloride and bicarbonate secretion into the intestinal lumen. Intestinal fluid increases and GI transit time is decreased. Increased extracellular cGMP may decrease visceral pain by reducing pain-sensing nerve activity.

Absorption

Minimal systemic availability; plasma concentrations are not measurable when used at recommended doses.

Distribution

Minimal tissue distribution is expected given immeasurable plasma concentrations when used at recommended doses.

Metabolism

Metabolized within GI tract to active metabolite; parent drug and metabolite undergo proteolytic degradation within the intestinal lumen to smaller peptides and amino acids

Excretion

Primarily feces (3% to 5%; as the active metabolite)

Use: Labeled Indications

Chronic idiopathic constipation: Treatment of chronic idiopathic constipation (CIC) in adults

Irritable bowel syndrome with constipation: Treatment of irritable bowel syndrome with constipation (IBS-C) in adults

Contraindications

Pediatric patients <6 years; mechanical gastrointestinal obstruction (known or suspected)

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to linaclotide or any component of the formulation

Dosing: Adult

Chronic idiopathic constipation (CIC): Oral: 145 mcg once daily; 72 mcg once daily may be used based on patient presentation or tolerability.

Irritable bowel syndrome with constipation (IBS-C): Oral: 290 mcg once daily.

Dosing: Geriatric

Refer to adult dosing; use with caution.

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

No dosage adjustment necessary.

Administration

Administer at least 30 minutes before the first meal of the day on an empty stomach; loose stools and greater stool frequency may occur after administration with a high-fat breakfast. Swallow capsule whole; do not break, crush, or chew capsules or capsule contents.

For patients with swallowing difficulties, capsules may be opened and administered orally either in applesauce or with water or administered with water via a nasogastric or gastric feeding tube. Mixing beads from capsules in other soft foods or in other liquids has not been tested.

Administration in applesauce: Open capsule and sprinkle entire contents (beads) onto 1 teaspoonful (5 mL) of room temperature applesauce. Swallow entire contents immediately; do not chew the beads. Do not store mixture for future use.

Administration in water: Open capsule and sprinkle entire contents (beads) into a cup with ~30 mL of room temperature bottled water. Gently swirl for at least 20 seconds and swallow immediately; add another 30 mL of water to any remaining beads in cup, swirl for at least 20 seconds, and swallow immediately. Do not store the water-bead mixture for future use. Note: The drug is coated on surface of beads and will dissolve off the beads in water; beads will remain visible and will not dissolve; therefore, it is not necessary to consume all the beads to deliver complete dose.

Administration via nasogastric or gastric feeding tube: Open capsule and empty entire contents (beads) into a clean container with 30 mL of room temperature bottled water. Gently swirl for at least 20 seconds; draw up bead and water mixture with catheter syringe and apply rapid and steady pressure (10 mL per 10 seconds) to dispense the bead-water mixture into the tube; add another 30 mL of water to any remaining beads and repeat process. Flush nasogastric/gastric tube with at least 10 mL of water after administration. Note: Not necessary to flush all the beads through tube to deliver complete dose.

Dietary Considerations

Administer at least 30 minutes before the first meal of the day on an empty stomach. Loose stools and greater stool frequency may occur after administration with a high-fat breakfast.

Storage

Store at 25°C (77°F) in tightly closed, original container with included desiccant packet; excursions permitted between 15°C and 30°C (59°F and 86°F). Do not subdivide or repackage; protect from moisture.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Adverse reactions reported with use in IBS-C and CIC.

>10%: Gastrointestinal: Diarrhea (16% to 22%)

1% to 10%:

Central nervous system: Headache (4%), fatigue (<2%)

Endocrine & metabolic: Dehydration (≤1%)

Gastrointestinal: Abdominal pain (7%), flatulence (4% to 6%), abdominal distension (2% to 3%), viral gastroenteritis (≤3%), severe diarrhea (2%), dyspepsia (<2%), fecal incontinence (<2%), gastroesophageal reflux disease (<2%), vomiting (<2%)

Respiratory: Upper respiratory tract infection (5%), sinusitis (3%)

<1%, postmarketing, and/or case reports: Hematochezia, hypersensitivity reaction, melena, nausea, rectal hemorrhage, urticaria

ALERT: U.S. Boxed Warning

Risk of serious dehydration in pediatric patients:

Linaclotide is contraindicated in pediatric patients less than 6 years; in nonclinical studies in neonatal mice, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration. Avoid use of linaclotide in patients 6 years to less than 18 years. The safety and effectiveness of linaclotide has not been established in patients less than 18 years.

Warnings/Precautions

Concerns related to adverse effects:

• Diarrhea: May cause diarrhea; severe diarrhea associated with dizziness, syncope, hypotension, and electrolyte abnormalities (hypokalemia and hyponatremia) requiring hospitalization or IV fluids has also been reported; consider discontinuation of therapy and rehydration if severe diarrhea occurs. Administration with a high-fat meal may worsen diarrhea.

Special populations:

• Pediatric patients: Serious dehydration: [US Boxed Warning]: Use is contraindicated in pediatric patients <6 years of age. Avoid use in pediatric patients 6 to 17 years. In studies in neonatal mice, administration of a single oral dose of linaclotide caused deaths due to dehydration. The safety and effectiveness of linaclotide has not been established in patients <18 years.

Monitoring Parameters

IBS-C: Abdominal pain, spontaneous bowel movement quality and frequency

CIC: Frequency of straining during bowel movements; spontaneous bowel movement quality and frequency

Pregnancy Considerations

Linaclotide and its metabolite are not measurable in plasma when used at recommended doses. Maternal use is not expected to result in fetal exposure.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience flatulence. Have patient report immediately to prescriber black, tarry, or bloody stools; severe diarrhea; persistent diarrhea, abdominal edema; bloating; severe abdominal pain; or signs of dehydration (dry skin, dry mouth, dry eyes, increased thirst, tachycardia, dizziness, fast breathing, or confusion) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Hide