Linaclotide
Package labels
Loading package label images…
Looking up MedlinePlus…
From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: PEDIATRIC RISK LINZESS is contraindicated in pediatric patients up to 6 years of age; in nonclinical studies, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration in young juvenile mice. Avoid use of LINZESS in pediatric patients 6 through 17 years of age. The safety and efficacy of LINZESS has not been established in pediatric patients under 18 years of age [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.4 ) and Nonclinical Toxicology ( 13.2 )]. WARNING: PEDIATRIC RISK See full prescribing information for complete boxed warning.
LINZESS is contraindicated in pediatric patients up to 6 years of age; linaclotide caused deaths due to dehydration in young juvenile mice. Avoid use of LINZESS in pediatric patients 6 through 17 years of age. The safety and efficacy of LINZESS has not been established in pediatric patients under 18 years of age ( 4 , 5.1 , 8.4 , 13.2 ).
Guanylate Cyclase-C Agonist
Dosing in kidney impairment
Hepatic or Renal Impairment No dose adjustment is necessary based on hepatic or renal function [see Clinical Pharmacology] .
Preparation and administration
Important Administration Instructions Do not crush or chew capsule or capsule contents. Swallow LINZESS capsule whole, or for adult patients with swallowing difficulties, follow the instructions below for administration with applesauce or water. Sprinkling of LINZESS beads on other soft foods or in other liquids has not been tested.
Do not crush or chew capsule or capsule contents. Swallow LINZESS capsule whole, or for adult patients with swallowing difficulties, follow the instructions below for administration with applesauce or water. Sprinkling of LINZESS beads on other soft foods or in other liquids has not been tested. For administration in applesauce: For administration in applesauce: Place one teaspoonful of applesauce at room temperature into a clean container.
Open the capsule. Sprinkle entire contents (beads) on applesauce. Consume the entire contents immediately. Do not chew the beads. Do not store the applesauce and beads for later use. For administration in water: For administration in water: Pour approximately 1 ounce (30 mL) of bottled water at room-temperature into a clean cup.
Open the capsule Sprinkle entire contents (beads) into the water Gently swirl beads and water for at least 10 seconds. Swallow the entire mixture of beads and water immediately. Add another 1 ounce of water to any beads remaining in cup, swirl for 10 seconds, and swallow immediately. Do not store the bead-water mixture for future use.
Note: The drug is coated on the surface of the beads and will dissolve off the beads into the water. The beads will remain visible and will not dissolve. Therefore, it is not necessary to consume all the beads to deliver the complete dose. Note: The drug is coated on the surface of the beads and will dissolve off the beads into the water.
The beads will remain visible and will not dissolve. Therefore, it is not necessary to consume all the beads to deliver the complete dose. For nasogastric or gastric feeding tube administration in water: For nasogastric or gastric feeding tube administration in water: Open the capsule and empty the beads into a clean container with 1 ounce (30 mL) of room-temperature bottled water.
Mix by gently swirling beads for at least 10 seconds Draw-up the beads and water mixture to an appropriately sized catheter-tipped syringe and apply rapid and steady pressure (10 mL/10 seconds) to dispense the 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 the complete dose. Note: It is not necessary to flush all the beads through to deliver the complete dose. After dosing of linaclotide in either applesauce or water, the first meal of the day can be consumed 30 minutes later. After dosing of linaclotide in either applesauce or water, the first meal of the day can be consumed 30 minutes later.
Drug interactions
Check interactions
Add the patient's other drugs. Matches come from both FDA labels: by name, drug class, and enzyme or transporter pathway.
- Linaclotide
Label text (1 paragraph)
No drug-drug interaction studies have been conducted with LINZESS. Linaclotide and its active metabolite are not measurable in plasma following administration of the recommended clinical doses; hence, no systemic drug-drug interactions or drug interactions mediated by plasma protein binding of linaclotide or its metabolite are anticipated [see Clinical Pharmacology ( 12.3 )] . Linaclotide does not interact with the cytochrome P450 enzyme system based on the results of in vitro studies. In addition, linaclotide is neither a substrate nor an inhibitor of the efflux transporter P-glycoprotein (P-gp).
Contraindications
4 CONTRAINDICATIONS LINZESS is contraindicated in: Pediatric patients under 6 years of age [see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.4 ) and Nonclinical Toxicology ( 13.2 )] Patients with known or suspected mechanical gastrointestinal obstruction Pediatric patients under 6 years of age ( 4 ) Patients with known or suspected mechanical gastrointestinal obstruction ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
ELikelihood score E: Unlikely cause of clinically apparent liver injury.
Linaclotide is small peptide agonist of guanylate cyclase C receptors in the intestine and is used orally as treatment of chronic constipation and irritable bowel syndrome. Linaclotide has not been linked to serum enzyme elevations during treatment or to episodes of clinically apparent liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Pregnancy Category C Risk Summary There are no adequate and well-controlled studies with LINZESS in pregnant women. In animal developmental studies, adverse fetal effects were observed only with maternal toxicity and at doses of linaclotide much higher than the maximum recommended human dose. LINZESS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal Data The potential for linaclotide to cause teratogenic effects was studied in rats, rabbits and mice. Oral administration of up to 100,000 mcg/kg/day in rats and 40,000 mcg/kg/day in rabbits produced no maternal toxicity and no effects on embryo-fetal development.
In mice, oral dose levels of at least 40,000 mcg/kg/day produced severe maternal toxicity including death, reduction of gravid uterine and fetal weights, and effects on fetal morphology. Oral doses of 5000 mcg/kg/day did not produce maternal toxicity or any adverse effects on embryo-fetal development in mice. The maximum recommended human dose is approximately 5 mcg/kg/day, based on a 60-kg body weight. Limited systemic exposure to linaclotide was achieved at the tested dose levels in animals (AUC = 40, 640, and 25 ng•hr/mL in rats, rabbits, and mice, respectively, at the highest dose levels), whereas no detectable exposure occurred in humans.
Therefore, animal and human doses should not be compared directly for evaluating relative exposure.
Lactation
8.3 Nursing Mothers It is not known whether linaclotide is excreted in human milk; however, linaclotide and its active metabolite are not measurable in plasma following administration of the recommended clinical doses [see Clinical Pharmacology ( 12.3 )] . Caution should be exercised when LINZESS is administered to nursing women [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.4 )].
Breastfeeding (LactMed)
Linaclotide is minimally absorbed from the gastrointestinal tract and the drug and its active metabolite are not measurable in milk following administration of doses up to 290 mcg daily. Linaclotide appears to be acceptable in nursing mothers and no special precautions are required.
- Lubiprostone
- Plecanatide
- Polyethylene Glycol
- Psyllium
- Tenapanor
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.