Linaclotide (Linzess) Medication for IBS: Uses, Dosage, Cost, Side effects

Linzess (Linaclotide)

Linaclotide (Linzess) is one of the novel medicines indicated for the treatment of chronic constipation and IBS with predominant symptoms of constipation.

Linzess Uses (Indications) in Adults

Irritable Bowel Syndrome with Constipation (IBS-C)
Chronic Idiopathic Constipation (CIC)

It is among the first of a new class of medicines that act primarily by increasing intestinal fluid content via activating chloride channels.

Linaclotide also increases gut movements and thereby reducing the transit time.

It reduces the visceral hypersensitivity relieving visceral pain which is the predominant symptom of IBS.

Linaclotide Dosage in Adults:

Linaclotide is available in three different dosage strengths and formulations:

  • 72 mcg
  • 145 mcg, and
  • 290 mcg

The recommended dose of Linzess in adults depends on the indication for which it is used.

For the treatment of CIC (chronic idiopathic constipation), the recommended dose is 290 mcg orally once daily before the first meal of the day.

For the treatment of IBS-C (Irritable bowel syndrome with constipation), the recommended dose is 145 mcg orally once a day before breakfast.

To avoid side effects and maximize drug tolerance, treatment may be initiated in a low dose for a week or so and then gradually titrated upwards to the usual recommended dose.

In patients who are prone to developing side effects, Linzess may be initiated in a dose of 72 mcg orally once a day [Ref].

Linzess (Linaclotide) Dose in Adults

Chronic Idiopathic Constipation (CIC)290 mcg orally once daily before breakfast
IBS- C (Irritable bowel syndrome with constipation145 mcg orally once daily before breakfast.

An initial few days of 72 mcg may be given to patients to increase tolerability.

How to take Linaclotide (Linzess)?

Linaclotide (Linzess) is available in the form of capsules that are taken orally once a day. The manufacturer recommends taking the capsule once a day before meals, preferably before the first meal of the day.

Double dosing or taking Linzess twice a day is not recommended. Even in patients who forget to take their medicines on time, taking the medicine at odd times such as taking Linzess after eating or at night before going to bed is not recommended.

Patients can wait for the next dose and take Linzess at their scheduled time.

Linzess capsules should not be opened or sprinkled on food. They should not be mixed or taken with fluids or beverages other than water and applesauce.

However, in patients who are being given nutrition via a nasogastric or orogastric tube, Linzess capsules can be opened, mixed with plain water, and administered via a nasogastric (NG) tube.

How to administer Linzess with water?

  • Take about 30 ml of clean water at room temperature.
  • Open the capsule and sprinkle the beads of the drug in it.
  • Mix it for about 20 seconds and swallow the entire contents.
  • Add another 30 ml of clean water and mix the remaining beads for another 20 seconds and then swallow it.
  • Do not store the mixture after opening the capsules.

How to administer Linzess with applesauce?

  • One teaspoonful of applesauce is taken.
  • It is mixed with Linzess, after opening the capsule and sprinkling Linzess beads over it.
  • The mixture is then swallowed without storing any of it.

It is not important but preferred to swallow all the beads since the drug is coated over the beads. After mixing it with water or applesauce, the medicine gets dissolved in water which is then ingested.

How to administer Linzess via an NG tube?

  • Take about 30 ml of clean water at room temperature.
  • Open the capsule and sprinkle the beads of the drug in it.
  • Mix it for about 20 seconds.
  • Draw the drug-mixed water via the appropriate feeding syringe and steadily push it through the NG tube.
  • Add another 30 ml of clean water and mix the remaining beads for another 20 seconds and then repeat the process of administering it via the NG tube or gastrostomy tube.
  • The feeding syringe can then be flushed with 10 ml of water.


Linzess Dose in Children:

Linzess is not recommended to be used in children who are younger than 18 years of age. Young individuals and especially children express more GCC (guanylate cyclase receptors) and hence they are prone to develop serious side effects.

The most important side effect of Linzess in young individuals is diarrhea and dehydration which may result in hypotension and shock.

It should be avoided in children younger than 18 years of age and is contraindicated in children who are 6 years of age or younger.

Linzess Dose in Kidney and Liver Diseases:

Linzess is not systemically absorbed and can be given to patients with kidney or liver diseases without the need for dose adjustment.

However, if diarrhea develops, it may worsen kidney functions. Therefore, diarrhea should be avoided.



Linzess Use in Pregnancy and Breastfeeding:

Linzess is minimally absorbed. It acts primarily on the luminal side of the intestinal mucosa. Since there is limited systemic exposure, it does not affect the fetus when administered in usual doses even during the period of organogenesis.

In animal studies, supranormal doses resulted in miscarriages and fetal malformation. In humans, data is very limited.

It should be avoided during pregnancy. Similarly, in breastfeeding mothers, data is very limited. Although minimally absorbed, its secretion into breast milk is not known.

Maternal diarrhea and dehydration should be avoided. It should be avoided in breastfeeding mothers because of limited safety data.



Linzess Contraindications:

Linzess is contraindicated in:

  • Young children who are six years of age or less
  • Individuals with signs and symptoms of intestinal obstruction.

Children are predisposed to developing severe dehydration. This may cause acute kidney injury, hypotension, and organ dysfunction. Deaths have been reported in children who are younger than 6 years of age.

Linzess Side Effects:

Linzess is minimally absorbed and hence has very few side effects. However, since it is used to treat constipation, it may cause severe diarrhea.

Severe dehydration:

In children, especially those younger than 6 years of age, Linzess has resulted in severe dehydration.

Linzess is not recommended for children and adolescents who are 18 years of age or younger. In children younger than 6 years of age and even up to 18 years of age, the GCC (guanylate cyclase-C) receptors are over-expressed.

Thus, younger individuals are susceptible to the side effects of Linzess. These patients may develop severe diarrhea and dehydration that may lead to hypotension, organ dysfunction, and death.


Since Linzess is used to treat constipation, diarrhea is one of the expected side effects of Linzess. In fact, diarrhea is an effect, especially of overtreatment or overdosage.

Diarrhea may sometimes be very severe and cause dehydration, syncope, and electrolyte imbalance including hypokalemia and hyponatremia.

In clinical trials, diarrhea occurred in 2% of the participants who took the 145 mcg or the 290 mcg capsules compared to those who took the placebo (<1%).

Gastrointestinal side effects:

Although diarrhea was the most common side effect, including severe diarrhea, other GI symptoms were also not uncommon.

The following table shows the frequency of GI-related side effects of Linzess compared to placebo:

Linzess Side effectsLinzess (290 mcg)Placebo
Abdominal pain7%5%
Abdominal distension2%1%
Viral gastroenteritis3%1%

5% of the participants discontinued the treatment because of diarrhea compared to 1% in the placebo group.

Other less common GI side effects of Linzess were:

  • Vomiting
  • GERD (gastroesophageal reflux disease)
  • Fecal incontinence
  • Fecal urgency

Post-marketing side effects of Linzess include:

  • Bleeding per rectum
  • Nausea
  • Allergic reactions
  • Urticaria, and Hives


Linaclotide MOA ( Mechanism of Action):

Linaclotide is a human GCC agonist (guanylate cyclase-C). It resembles guanylin and uroguanylin. The binding of Linaclotide and its metabolites to the GCC receptors increases the intracellular and extracellular cGMP.

The activation of cGMP results in the pouring of chloride and bicarbonate-rich fluid into the intestinal lumen primarily via the CFTR ion channel (cystic fibrosis transmembrane conductance regulator ion channel).

Thus, it softens the stools and increases gut motility via its direct action on the intestinal mucosa.

Via the extracellular cGMP activation and direct effects on the neuronal endings present in the intestinal mucosa and smooth muscles, Linzess also relaxes the smooth muscles and relieves intestinal spasms and abdominal pain.

Absorption and Distribution:

Linaclotide is not distributed into the tissues because of minimal to no absorption.

Metabolism and Excretion:

Linzess is metabolized into its active metabolite in the intestinal lumen. Both Linzess and its active metabolites are metabolized by proteolytic cleavage into smaller peptides and amino acids.

The metabolites are then excreted in feces.



Linaclotide Brand Names and Price:

It is available by the brand names of:

  • Linzess, and
  • Constella

as oral capsules of 72 mcg, 145 mcg, and 290 mcg.

Linzess Price:

Each capsule of Linzess costs around USD 14 to USD 18. The average per-month cost of Linzess is about USD $500 per 30 capsules.

Costella Price:

Costella (Linaclotide) Price

Strength of tablets145 mcg290 mcg
Per Day cost (Per tablet price)USD 4USD 6
Per Month cost (Per 30 tablet price)USD 150USD 199
Per 3-month cost (Per 90 tablet price)USD 450USD 597

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Written by Dr. Ahmed

I am Dr. Ahmed (MBBS; FCPS Medicine), an Internist and a practicing physician. I am in the medical field for over fifteen years working in one of the busiest hospitals and writing medical posts for over 5 years.

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