For adults with Chronic Idiopathic Constipation (CIC)

Activate 5-HT₄ receptors and stimulate colonic peristalsis.^1,4*

*Motegrity is a selective serotonin type 4 (5-HT₄) receptor agonist.¹

Motegrity Mechanism of Action

How does Motegrity work?

Motegrity provides a different class of CIC treatment that works by stimulating colonic peristalsis to increase bowel motility.^1-4

Here’s how:

1 Absorb

One 2 mg oral dose of Motegrity in healthy participants reached peak plasma concentrations within 2-3 hours.¹

Click here for median time-to-first bowel movement

3D representation of
prucalopride

2 Activate

In the colon, Motegrity selectively binds and activates 5-HT₄ receptors^1,4,5

Motegrity showed no cross-reactivity with 5-HT_2A, 5-HT_2B, 5-HT₃, motilin, or CCK-A receptors in in vitro studies at concentrations exceeding 5-HT₄ receptor affinity by 150-fold or greater.^1,6

3 Release

Colonic 5-HT₄ receptor activation facilitates the release of acetylcholine as seen in in vitro studies^1,4,5

4 Move

Colonic peristalsis is stimulated, increasing bowel motility^1,4,5

Treatment mechanisms in the management of chronic idiopathic constipation

Osmotic laxatives

Prosecretory agents

Serotonergic agents

Treatment mechanisms in CIC management. Osmotic laxatives create an osmotic gradient, drawing water into the intestinal lumen

GC-C agonist

CLC-2 agonist

5-HT₄receptor agonist

Treatment mechanisms in CIC management. Serotonergic agents promote ACh release, colonic contractions and peristalsis

Create an osmotic gradient that draws water into the intestinal lumen.^2,7,8

Activate GC-C receptors, leading to increased secretion of Cl^- and HCO₃^-, followed by Na⁺ and water.^2,7,9,10

Activate CLC-2 channels, increasing Cl^-secretion, followed by Na⁺ and water.^2,7,10

Activate 5-HT₄receptors, promoting ACh release, colonic smooth muscle contractions and peristalsis.^1,2,4,5

Overview of treatment mechanisms is not a comparison of treatment safety or efficacy.
These are not all the current treatments or rescue medications for adults with CIC.

The above are illustrations of colons. The diagrams are a simplified representation of the purported primary MOA.

ACh=acetylcholine; CFTR=cystic fibrosis transmembrane conductance regulator; cGMP=cyclic guanosine monophosphate; CLC-2=chloride channel-type 2; GC-C=guanylate cyclase‑C; HAPC=high amplitude propagating contraction.

Osmotic laxatives

Create an osmotic gradient that draws water into the intestinal lumen.^2,7,8

Prosecretory agents

GC-C agonist

Activate GC-C receptors, leading to increased secretion of Cl^- and HCO₃^-, followed by Na⁺ and water.^2,7,9,10

Prosecretory agents

CLC-2 agonist

Activate CLC-2 channels, increasing Cl^- secretion, followed by Na⁺ and water.^2,7,10

Serotonergic agents

5-HT₄ receptor agonist

Activate 5-HT₄ receptors, promoting ACh release, colonic smooth muscle contractions and peristalsis.^1,2,4,5

Overview of treatment mechanisms is not a comparison of treatment safety or efficacy.
These are not all the current treatments or rescue medications for adults with CIC.

The above are illustrations of colons. The diagrams are a simplified representation of the purported primary MOA.

Want to learn more about
how Motegrity works?

Discover our prokinetic approach by watching these 3 short videos

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3:35

Motegrity—A Motility Based Mechanism of Action

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4:04

Motegrity—A 5-HT4 Receptor Agonist Prokinetic for Adults with CIC

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3:34

Colonic Motility and Accelerated Transit Time

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Your patients can benefit from a trial. Order a 7-day sample to get started.

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Pharmacodynamics of Motegrity

Motegrity is a GI prokinetic that stimulates colonic peristalsis (i.e. HAPCs), which increases bowel motility

In a pharmacodynamic CIC study:

More frequent HAPCs

A single 2 mg dose of Motegrity increased HAPC frequency during the first 12 hours compared to osmotic laxatives.¹

Increased HAPC amplitude

Motegrity 4 mg^* once daily for 7 days increased HAPC amplitude in healthy participants compared to placebo without affecting colonic phasic activity.¹

^*Twice the max recommended dose of 2 mg.

Accelerate colonic transit time (CTT) in adults with CIC^1,11

The effect of once daily Motegrity 2 mg and placebo on mean CTT was studied in an integrated analysis of 3 randomized, placebo-controlled, dose-finding trials in adults (n=280) with CIC. Mean CTT was reduced by 12 hours from a baseline of 65 hours for the Motegrity 2 mg group, compared to an increase of 0.5 hours from a baseline of 66 hours in the placebo group.^1,11

^†P<0.001 vs. baseline.

A closer look at the colonic 5-HT pathway

95% of endogenous 5-HT is found in the digestive tract¹²
5-HT is released by enterochromaffin cells in response to distension and other stimuli¹³
There are 5 families of 5-HT receptors in the gut that mediate a number of basic functions, including colonic motility^4,14
Colonic peristalsis is promoted when 5-HT₄ receptor activation stimulates acetylcholine release^4,5

Request Samples

Interested in receiving
samples of Motegrity?

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Formulary Coverage

Wondering which plans in your area cover Motegrity? See our patient access coverage tool to find out more.

Patient access coverage tool

IMPORTANT SAFETY INFORMATION

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Please expand for Indication and Important Safety Information.

Contraindications

Hypersensitivity to Motegrity. Reactions including dyspnea, rash, pruritus, urticaria, and facial edema have been observed
Intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the intestinal tract such as Crohn's disease, ulcerative colitis, and toxic megacolon/megarectum

Warnings and Precautions

Suicidal Ideation and Behavior: In clinical trials, suicides, suicide attempts and suicidal ideation have been reported. Postmarketing cases of suicidal ideation and behavior as well as self-injurious ideation and new onset or worsening of depression have been reported within the first few weeks of starting Motegrity. A causal association between treatment with Motegrity and an increased risk of suicidal ideation and behavior has not been established. Monitor patients for new onset or worsening of depression and emergence of suicidal thoughts and behavior. Instruct patients to discontinue Motegrity immediately and contact their healthcare provider if they experience any of these symptoms.

Adverse Reactions

Most common adverse reactions (≥2%) are headache, abdominal pain, nausea, diarrhea, abdominal distension, dizziness, vomiting, flatulence, and fatigue.

Use in Specific Populations

Lactation: Motegrity is present in breast milk. Consider risks and benefits of breastfeeding
Pediatric: Safety and effectiveness in pediatric patients have not been established
Renal Impairment: A decreased dosage is recommended in patients with severe renal impairment. Avoid Motegrity in patients with end-stage renal disease requiring dialysis

INDICATION

Motegrity® (prucalopride) is a serotonin-4 (5-HT₄) receptor agonist indicated for the treatment of chronic idiopathic constipation (CIC) in adults.

Please click here for full Prescribing Information.

References:

1. Motegrity (prucalopride) Prescribing Information. Lexington, MA: Takeda Pharmaceuticals America, Inc. 2. Camilleri M, Ford AC, Mawe GM, et al. Nat Rev Dis Primers. 2017;3:17095. 3. Tack J, Camilleri M, Chang L, et al. Aliment Pharmacol Ther. 2012;35(7):745-767. 4. Mawe GM, Hoffman JM. Nat Rev Gastroenterol Hepatol. 2013;10(8):473-486. 5. Gershon MD, Tack J. Gastroenterology. 2007;132(1):397-414. 6. Briejer MR, Bosmans JP, Van Daele P, et al. Eur J Pharmacol. 2001;423(1):71-83. 7. Lacy B, Hussain Z, Mearin F. Neurogastroenterol Motil. 2014;26(6):749-763. 8. Izzy M, Malieckal A, Little E, et al. World J Gastrointest Pharmacol Ther. 2016;7(2):334-342. 9. Lacy BE, Levenick JM, Crowell M. Therap Adv Gastroenterol. 2012;5(4):233-247. 10. Menees S, Saad R, Chey WD. Nat Rev Gastroenterol Hepatol. 2012;9(11):661-674. 11. Emmanuel A, Cools M, Vandeplassche L, Kerstens R. Am J Gasteroenterol. 2014;109(6):887-894. 12. Kim DY, Camilleri M. Am J Gastroenterol. 2000;95(10):2698-2709. 13. Kim HS. J Smooth Muscle Res. 2009;45(1):25-29. 14. Kendig DM, Grider JR. Neurogastroenterol Motil. 2015;27(7):899-905.

Activate 5-HT4 receptors and stimulate colonic peristalsis.1,4*

Motegrity Mechanism of Action

Here’s how:

3D representation of prucalopride

Treatment mechanisms in the management of chronic idiopathic constipation

Osmotic laxatives

Prosecretory agents

Prosecretory agents

Serotonergic agents

Want to learn more about how Motegrity works?

Now playing

3:35

Motegrity—A Motility Based Mechanism of Action

Now playing

4:04

Motegrity—A 5-HT4 Receptor Agonist Prokinetic for Adults with CIC

Now playing

3:34

Colonic Motility and Accelerated Transit Time

SELECT IMPORTANT SAFETY INFORMATION

Adverse Reactions

Pharmacodynamics of Motegrity

Motegrity is a GI prokinetic that stimulates colonic peristalsis (i.e. HAPCs), which increases bowel motility

In a pharmacodynamic CIC study:

More frequent HAPCs

Increased HAPC amplitude

*Twice the max recommended dose of 2 mg.

Accelerate colonic transit time (CTT) in adults with CIC1,11

†P<0.001 vs. baseline.

A closer look at the colonic 5-HT pathway

Request Samples

Formulary Coverage

By following this link you will be leaving a Takeda controlled website for a third party website

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IMPORTANT SAFETY INFORMATION

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Activate 5-HT₄ receptors and stimulate colonic peristalsis.^1,4*

3D representation of
prucalopride

Want to learn more about
how Motegrity works?

^*Twice the max recommended dose of 2 mg.

Accelerate colonic transit time (CTT) in adults with CIC^1,11

^†P<0.001 vs. baseline.