For adults with Chronic Idiopathic Constipation (CIC)

Safety profile studied in 2530 adult
and elderly patients with CIC

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
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Safety and Tolerability

The safety and tolerability profile of Motegrity was studied in 2530 patients (Motegrity 2 mg once-daily [N=1251], placebo [N=1279]) with CIC across 6 double-blind, placebo-controlled clinical trials of 12 to 24 weeks duration. Overall, most patients were female (76%) and Caucasian (76%), with a mean age of 47 years (range 17 to 95).1

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.1

No overall differences in safety and effectiveness were observed between elderly and younger patients. Adjust the dosage in elderly patients based on renal function. Avoid Motegrity in patients with end-stage renal disease requiring dialysis.1

Common adverse reactions* reported in patients receiving Motegrity 2 mg or placebo1

Results from double-blind, placebo-controlled trials of CIC of at least 12 weeks duration

Adverse
Reaction
Motegrity 2 mg
once daily
(N=1251)
placebo
(N=1279)
Headache 19% 9%
Abdominal Pain 16% 11%
Nausea 14% 7%
Diarrhea 13% 5%
Abdominal Distension 5% 4%
Dizziness 4% 2%
Vomiting 3% 2%
Flatulence 3% 2%
Fatigue 2% 1%

*Reported in ≥‍2% of patients receiving Motegrity and a rate higher than patients receiving placebo.
Includes 93 patients who started on Motegrity 1 mg and increased to Motegrity 2 mg.
Includes abdominal pain, upper abdominal pain, lower abdominal pain, abdominal tenderness, abdominal discomfort, and epigastric discomfort.

Less common adverse reactions reported in <2% of patients receiving Motegrity 2 mg once daily included: abnormal GI sounds, decreased appetite, migraine and pollakiuria.

If reported within the first week of treatment, adverse events of diarrhea or headache typically resolved within a few days.1

The majority of patients who reported diarrhea did so in the first week of treatment (n=110/157), and the majority who reported headache did so in the first two days of treatment (n=157/237). For these patients, symptoms typically resolved within a few days (n=80/110 for diarrhea; n=102/157 for headache).1

Severe diarrhea was reported in 1.8% of patients treated with Motegrity 2 mg compared to 1% of patients in the placebo group, and had a similar onset and duration as diarrhea overall.1

Overall, discontinuation due to adverse events was low (5% Motegrity 2 mg once daily, 3% placebo).1

Cardiovascular Safety Analysis

Cardiovascular safety of Motegrity was evaluated in a MACE analysis of the double-blind, placebo-controlled and open-label studies, as well as in a retrospective observational study which demonstrated no increase in the risk of MACE with Motegrity relative to polyethylene glycol (PEG).1

Description
Endpoint
Trial Result

Description: Independent adjudication committee evaluation of all potential MACE in 19 double-blind and 9 open-label Motegrity trials (0.5 mg, 1 mg, 2 mg or 4 mg per day in adult patients with CIC. The recommended dosage of Motegrity is 2 mg once daily)

Endpoint: Standardized incidence rate (IR) per 1,000 patient-years for MACE for Motegrity vs. placebo

Trial Result:

Motegrity IR in double-blind trials: 3.5
(n=2/3366; 1 patient on 2 mg, 1 patient on 4 mg§)

Placebo IR in double-blind trials: 5.2
(n=2/2019)

Motegrity IR in combined double-blind and open-label trials: 3.3
(n=9/4472; doses ranging between 0.5 – 4 mg§)

Description: Population-based, retrospective observational, cohort study of adults with constipation, using European healthcare databases, which assessed the overall cardiovascular safety of Motegrity. New users of Motegrity (N=5715) were matched to new users of PEG (N=29,372) to estimate the SIRR for MACE

Endpoint: Standardized incidence rate ratio (SIRR) for MACE, pooled across four data sources from European healthcare databases

Trial Result:

Motegrity relative to PEG
The 95% confidence interval for the pooled estimate of the SIRR did not demonstrate an increased MACE risk and excluded a pre-specified safety margin of a three-fold risk of MACE during prucalopride use relative to PEG use

MACE=Major Adverse Cardiovascular Events, which were defined as: cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.1

§2X max recommended dose of 2 mg. PEG=polyethylene glycol 3350

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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.

Reference:

1. Motegrity (prucalopride) Prescribing Information. Lexington, MA: Shire LLC.