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

Arrow
Colonic 5-HT4 receptor
2Activate
In the colon, Motegrity activates 5‍-‍HT‍4 receptors1,4,5
Illustrative 5-HT4 receptor in cell membrane
Arrow
3Release
Colonic 5‍-‍HT‍4 receptor activation facilitates
the release of acetylcholine
as seen in in vitro studies1,4,5
Arrow
Colonic peristalsis
4Move
Colonic peristalsis is enhanced, increasing
bowel motility
1,4,5

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

Motegrity enhances natural movements
of the colon muscle (peristalsis).1,4,5

Want to see more?
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.

Molecule

Selectively activates
the 5-HT4 receptor1,6

Motegrity binds with high-affinity to 5-HT4 receptors and 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

Motegrity reduced
mean colonic transit time (CTT)

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

Graph showing change in mean colonic transit time against placebo Graph showing change in mean colonic transit time against placebo

A closer look at the colonic 5-HT pathway

95% of endogenous 5‍-‍HT
is found in the digestive tract7

5-HT is released by
enterochromaffin cells

in response to distension
and other stimuli8

There are 5 families of
5‍-‍HT
receptors
in the gut
that mediate
a number
of basic functions,
including
colonic motility4,9,10

5-HT4 receptor activation stimulates acetylcholine release, promoting colonic peristalsis4,5

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. Tack J, Camilleri M, Chang L, et al. Aliment Pharmacol Ther. 2012;35(7):745-767. 3. Camilleri M, Ford AC, Mawe GM, et al. Nat Rev Dis Primers. 2017;3:17095. 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. Kim DY, Camilleri M. Am J Gastroenterol. 2000;95(10):2698-2709. 8. Kim HS. J Smooth Muscle Res. 2009;45(1):25-29. 9. Kendig DM, Grider JR. Neurogastroenterol Motil. 2015;27(7):899-905. 10. Pytliak M, Vargová V, Mechírová V, Felšöci M. Physiol Res. 2011;60(1):15-25.