Linaclotide

Irritable Bowel Syndrome with Constipation (IBS-C)

Linaclotide (Linaclotide) is indicated in adults for the treatment of irritable bowel syndrome with constipation (IBS-C).

Chronic Idiopathic Constipation (CIC)

Linaclotide is indicated in adults for the treatment of chronic idiopathic constipation (CIC).

Linaclotide (Linaclotide) works by increasing the secretion of chloride and water in the intestines, which can soften stools and stimulate bowel movements.

Linaclotide is a prescription medicine used to treat chronic constipation, or chronic irritable bowel syndrome (IBS) in adults who have had constipation as the main symptom. The safety and effectiveness of Linaclotide has not been established in patients under 18 years of age.

Irritable Bowel Syndrome with Constipation (IBS-C)

The recommended dose of Linaclotide is 290 mcg taken orally once daily on an empty stomach, at least 30 minutes prior to the first meal of the day.

Chronic Idiopathic Constipation (CIC)

The recommended dose of Linaclotide is 145 mcg taken orally once daily on an empty stomach, at least 30 minutes prior to the first meal of the day.

Important Administration Instructions

​Do not crush or chew capsule or capsule contents. Swallow Linaclotide capsule whole, or for adult patients with swallowing difficulties, follow the instructions below for administration with applesauce or water. Sprinkling of Linaclotide beads on other soft foods or in other liquids has not been tested.

​For administration in applesauce:

1. ​Place one teaspoonful of applesauce at room temperature into a clean container.
2. ​Open the capsule.
3. ​Sprinkle entire contents (beads) on applesauce.
4. ​Consume the entire contents immediately. Do not chew the beads. Do not store the applesauce and beads for later use.

​For administration in water:

1. ​Pour approximately 1 ounce (30 mL) of bottled water at room-temperature into a clean cup.
2. ​Open the capsule
3. ​Sprinkle entire contents (beads) into the water
4. ​Gently swirl beads and water for at least 10 seconds.
5. ​Swallow the entire mixture of beads and water immediately.
6. ​Add another 1 ounce of water to any beads remaining in cup, swirl for 10 seconds, and swallow immediately.
7. ​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.

​For nasogastric or gastric feeding tube administration in water:

1. ​Open the capsule and empty the beads into a clean container with 1 ounce (30 mL) of room-temperature bottled water.
2. ​Mix by gently swirling beads for at least 10 seconds
3. ​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.
4. ​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.

​After dosing of Linaclotide in either applesauce or water, the first meal of the day can be consumed 30 minutes later.

See also:
What is the most important information I should know about Linaclotide?

You should not use Linaclotide if you are allergic to it, or if you have a blockage in your stomach or intestines.

Do not give this medication to any child or teenager without the advice of a doctor.

Take Linaclotide in the morning on an empty stomach, at least 30 minutes before your first meal. Do not crush, chew, break, or open a Linaclotide capsule. Swallow it whole.

Stop using Linaclotide and call your doctor at once if you have severe or ongoing diarrhea, severe stomach pain, or black, bloody, or tarry stools.

Use Linaclotide as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Linaclotide comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Linaclotide refilled.
• Take Linaclotide by mouth on an empty stomach at least 30 minutes before the first meal of the day.
• Swallow Linaclotide whole. Do not break apart, crush, or chew before swallowing.
• If you miss a dose of Linaclotide, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Linaclotide.

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

See also:
What other drugs will affect Linaclotide?

No drug-drug interaction studies have been conducted with Linaclotide. 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.

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).

See also:
What are the possible side effects of Linaclotide?

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.

During clinical development, approximately 2570, 2040, and 1220 patients with either IBS-C or CIC were treated with Linaclotide for 6 months or longer, 1 year or longer, and 18 months or longer, respectively (not mutually exclusive).

Irritable Bowel Syndrome with Constipation (IBS-C)

Most Common Adverse Reactions

The data described below reflect exposure to Linaclotide in the two placebo-controlled clinical trials involving 1605 adult patients with IBS-C (Trials 1 and 2). Patients were randomized to receive placebo or 290 mcg Linaclotide once daily on an empty stomach for up to 26 weeks. Demographic characteristics were comparable between treatment groups. Table 1 provides the incidence of adverse reactions reported in at least 2% of IBS-C patients in the Linaclotide treatment group and at an incidence that was greater than in the placebo group.

Table 1: Adverse Reactions Reported in at least 2% of Linaclotide-treated Patients and at an Incidence Greater than in Placebo Group Patients in the Two Phase 3 Placebo-controlled Trials (1 and 2) in IBS-C

Diarrhea

Diarrhea was the most commonly reported adverse reaction of the Linaclotide-treated patients in the pooled CIC placebo-controlled trials. In these trials, 16% of Linaclotide-treated patients reported diarrhea compared to 5% of placebo-treated patients. Severe diarrhea was reported in 2% of the 145 mcg Linaclotide-treated patients versus less than 1% of the placebo-treated patients, and 5% of Linaclotide-treated patients discontinued due to diarrhea vs less than 1% of placebo-treated patients. The majority of reported cases of diarrhea started within the first 2 weeks of Linaclotide treatment. Fecal incontinence was reported in 1% of patients in the Linaclotide treatment group, compared with less than 1% in the placebo group. Dehydration was reported in less than 1% of patients in the Linaclotide treatment group.

Adverse Reactions Leading To Discontinuation

In placebo-controlled trials in patients with CIC, 8% of patients treated with Linaclotide and 4% of patients treated with placebo discontinued prematurely due to adverse reactions. In the 145 mcg Linaclotide treatment group, the most common reasons for discontinuation due to adverse reactions were diarrhea (5%) and abdominal pain (1%). In comparison, less than 1% of patients in the placebo group withdrew due to diarrhea or abdominal pain.

Adverse Reactions Leading To Dose Reductions

In the open-label, long-term trials, 1129 patients with CIC received 290 mcg of Linaclotide daily for up to 18 months. In these trials, 27% of patients had their dose reduced or suspended secondary to adverse reactions, the majority of which were diarrhea or other GI adverse reactions.

Other Adverse Reactions

Adverse reactions that were reported in at least 1% of and less than 2% of CIC patients in the 145 mcg Linaclotide treatment group and at an incidence greater than in the placebo treatment group are listed below by body system:

Gastrointestinal Disorders: dyspepsia, fecal incontinence

Infections and Infestations: viral gastroenteritis

Other Adverse Events

In placebo-controlled trials in patients with CIC, less than 1% of both Linaclotide-treated and placebo-treated patients reported rectal hemorrhage, hematochezia or melena. Less than 1% of Linaclotide-treated and placebo-treated patients reported allergic reactions, urticaria, or hives as adverse events.

Linaclotide is an orally administered, peptide agonist of guanylate cyclase 2C for the treatment of irritable bowel syndrome. Chemically, it is a heterodetic cyclic peptide and consists of fourteen amino acids. The protein sequence is as follows: Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr. There are three disulfide bonds which are located between Cys1 and Cys6; between Cys2 and Cys10; and between Cys5 and Cys13. FDA approved on August 30, 2012.