Motegrity (Prucalopride) Indication
Motegrity (prucalopride) is FDA-approved for the treatment of chronic idiopathic constipation (CIC) in adults. 1
Primary Indication
- Prucalopride is specifically indicated for chronic idiopathic constipation in adults, where "idiopathic" means the cause of constipation is unknown 1
- The medication is typically reserved for patients who have not responded adequately to over-the-counter (OTC) laxatives 2
Mechanism of Action
- Prucalopride is a selective, high-affinity serotonin 5-HT4 receptor agonist that promotes neurotransmission by enteric neurons, resulting in stimulation of the peristaltic reflex, intestinal secretions, and gastrointestinal motility 2
- This mechanism directly stimulates colonic motility, differentiating it from other medications approved for chronic constipation (which are exclusively osmotic or chloride secretagogues) 3
Position in Treatment Algorithm
- The American Gastroenterological Association and American College of Gastroenterology provide a strong recommendation for prucalopride in adults with CIC who do not respond to OTC agents 2
- Prucalopride can be used as a replacement or as an adjunct to OTC agents 2
- The treatment hierarchy typically starts with osmotic laxatives (polyethylene glycol, lactulose, magnesium salts), then progresses to prescription agents like linaclotide, plecanatide, or prucalopride if OTC options fail 4, 5
Dosing and Administration
- The standard dose is 2 mg once daily, taken with or without food 2, 1
- A 1 mg dose is available for patients with renal impairment (creatinine clearance <30 mL/min) 1
- Duration of treatment in trials was 4-24 weeks, and the drug label does not provide a treatment duration limit 2
Efficacy Evidence
- Prucalopride increases complete spontaneous bowel movements (CSBMs) by approximately 1 per week compared to placebo (mean difference 0.96,95% CI 0.64-1.29) 2
- Responder rates (≥3 CSBMs per week) are significantly higher with prucalopride versus placebo (RR 2.37,95% CI 1.97-2.85), with 165 more responders per 1,000 patients 2
- Improvement in bowel movement frequency is typically seen as early as week 1 and maintained through 12 weeks 1
- The median time to first CSBM after initial dosing ranges from 1.4 to 4.7 days with prucalopride compared to 9.1 to 20.6 days with placebo 1
Common Side Effects
- The most common adverse effects include headache, nausea, dizziness, gas, abdominal pain or bloating, diarrhea, vomiting, and fatigue 1
- Diarrhea leading to treatment discontinuation occurs more frequently with prucalopride (RR 3.00,95% CI 1.89-4.78) 2
- Most side effects occur at the start of treatment and are usually transient 2
Critical Safety Warnings
- Prucalopride carries a boxed warning for suicidal ideation and behavior: patients, caregivers, and family members must be counseled about unusual mood changes, worsening depression, or emergence of suicidal thoughts 1
- The medication must be discontinued immediately if depression worsens or suicidal thoughts develop 1
Contraindications
- Absolute contraindications include: bowel perforation, intestinal obstruction, serious inflammatory bowel conditions (Crohn's disease, ulcerative colitis), and allergy to prucalopride 1
Special Populations
- Prucalopride demonstrates efficacy across age groups, including elderly patients ≥65 years, with no clear differences in outcomes 2, 6
- Efficacy is maintained regardless of body mass index or renal function (though dose adjustment is needed for severe renal impairment) 6
- Safety and effectiveness in children have not been established 1