For adults with Chronic Idiopathic Constipation (CIC)

Activate 5-HT4 receptors and enhance
colonic peristalsis.*

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

Select 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

Mechanism of Action

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

Here’s how:

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

Click here for median time-to-first bowel movement

Molecule
2Activate
In the colon, Motegrity selectively binds
and activates 5‍-‍HT‍4 receptors1,4,5

Motegrity showed no cross-reactivity with 5-HT2A, 5-HT2B, 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

3Release
Colonic 5‍-‍HT‍4 receptor activation facilitates the
release of acetylcholine
as seen in in vitro studies1,4,5
4Move
Colonic peristalsis is enhanced,
increasing bowel motility
1,4,5

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Watch this motion graphic video

Motegrity mechanism of action video thumbnail

Select Important Safety Information

Warnings and Precautions

Suicidal Ideation and Behavior: In clinical trials, suicides, suicide attempts and suicidal ideation have been reported. A causal association between treatment with Motegrity and an increased risk of suicidal ideation and behavior has not been established. Monitor patients for persistent worsening of depression and emergence of suicidal thoughts and behavior. Instruct patients to discontinue Motegrity immediately and contact their healthcare provider if their depression is persistently worse, or they experience emerging suicidal thoughts or behaviors.

Pharmacodynamics of Motegrity

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

Increased HAPCs
vs. osmotic laxative treatment

In a pharmacodynamic study in patients with CIC,
a single 2 mg dose of Motegrity increased the number of high amplitude propagating contractions (HAPCs) during the first 12 hours vs. an osmotic laxative treatment.1

Increased HAPC amplitude
vs. placebo

Treatment with Motegrity 4 mg once daily (2X max recommended dose of 2 mg) for 7 days increased the amplitude of HAPCs in healthy subjects without affecting colonic phasic activity vs. placebo.1

Accelerate colonic transit time (CTT) in adults with CIC1

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

Motegrity 2 mg reduced mean CTT by 12 hrs vs. baseline1

Faster colonic transit

-12
0.5

Treatment mechanisms
in the management of CIC

Osmotic laxatives

Treatment mechanisms in CIC management. Osmotic laxatives create an osmotic gradient, drawing water into the intestinal lumen
Create an osmotic gradient that draws water
into the intestinal lumen.2,7,8
Treatment mechanisms in CIC management. Osmotic laxatives create an osmotic gradient, drawing water into the intestinal lumen

Prosecretory agents

GC-C agonist

Treatment mechanisms in CIC management. Prosecretory agents. GC-C agonists activate GC-C receptors, leading to increased secretion of Cl- and HCO3-, followed by Na+ and water. CLC-2 agonists activate CLC-2 channels, increasing Cl- secretion, followed by Na+ and water
Activate GC-C receptors, leading to increased secretion of Cl- and HCO3-, followed by Na+ and water.2,7,9,10
Treatment mechanisms in CIC management. Prosecretory agents. GC-C agonists activate GC-C receptors, leading to increased secretion of Cl- and HCO3-, followed by Na+ and water. CLC-2 agonists activate CLC-2 channels, increasing Cl- secretion, followed by Na+ and water

CLC-2 agonist

Activate CLC-2 channels, increasing Cl- secretion, followed by Na+ and water.2,7,10
Treatment mechanisms in CIC management. Prosecretory agents. GC-C agonists activate GC-C receptors, leading to increased secretion of Cl- and HCO3-, followed by Na+ and water. CLC-2 agonists activate CLC-2 channels, increasing Cl- secretion, followed by Na+ and water

Serotonergic agents

5-HT4 receptor agonist

Treatment mechanisms in CIC management. Serotonergic agents promote ACh release, colonic contractions and peristalsis
Activate 5-HT4 receptors, promoting ACh release, colonic smooth muscle contractions and peristalsis.1,2,4,5
Treatment mechanisms in CIC management. Serotonergic agents promote ACh release, colonic contractions and peristalsis

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.

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Formulary Coverage

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cover Motegrity? See our patient access coverage tool to find out more.

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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. A causal association between treatment with Motegrity and an increased risk of suicidal ideation and behavior has not been established. Monitor patients for persistent worsening of depression and emergence of suicidal thoughts and behavior. Instruct patients to discontinue Motegrity immediately and contact their healthcare provider if their depression is persistently worse, or they experience emerging suicidal thoughts or behaviors.

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 is 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: Shire LLC. 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  Kim DY, Camilleri M. Am J Gastroenterol. 2000;95(10):2698-2709. 12  Kim HS. J Smooth Muscle Res. 2009;45(1):25-29. 13  Kendig DM, Grider JR. Neurogastroenterol Motil. 2015;27(7):899-905. 14  Pytliak M, Vargová V, Mechírová V, Felšöci M. Physiol Res. 2011;60(1):15-25.