What is Motegrity (prucalopride)?

Motegrity (Prucalopride): A Medication for Chronic Idiopathic Constipation

Motegrity (prucalopride) is a selective serotonin 5-HT4 receptor agonist that stimulates colonic peristalsis to increase bowel motility and is FDA-approved for the treatment of chronic idiopathic constipation (CIC) in adults. 1, 2

Mechanism of Action

• Prucalopride works as a gastrointestinal prokinetic agent that stimulates colonic peristalsis by activating 5-HT4 receptors, which increases high-amplitude propagating contractions (HAPCs) in the colon 1
• Unlike other constipation medications that work as osmotic agents or secretagogues, prucalopride directly stimulates colonic motility, providing a different mechanism of action 3
• The medication facilitates acetylcholine release to enhance the amplitude of contractions and stimulate peristalsis throughout the GI tract 1

Dosing and Administration

• Standard adult dose: 2 mg orally once daily 4
• Dose for severe renal impairment (creatinine clearance <30 mL/min): 1 mg once daily 4
• No dose adjustment needed based on age - efficacy in elderly patients (≥65 years) is comparable to the overall adult population 2
• Can be taken with or without food 1

Clinical Efficacy

• Increases complete spontaneous bowel movements (CSBMs) per week compared to placebo (mean difference 0.96,95% CI 0.64–1.29) 4
• Responder rates (patients achieving ≥3 CSBMs per week) are significantly higher with prucalopride compared to placebo (RR 2.37,95% CI 1.97–2.85) 4
• Improvement in bowel function is typically seen as early as week 1 and maintained through week 12 1
• Also improves constipation symptoms, abdominal symptoms, quality of life, and treatment satisfaction compared to placebo 2
• The 4 mg dose offers no additional benefit over the 2 mg dose for most patients 4

Side Effects and Safety

• Most common side effects include headache, nausea, dizziness, abdominal pain/bloating, diarrhea, vomiting, and fatigue 1
• Side effects typically occur during the first week of treatment and often resolve within a few days 2, 4
• Approximately 5% of individuals discontinue prucalopride because of side effects 2
• Unlike older 5-HT4 agonists (cisapride, tegaserod), prucalopride has not shown significant cardiovascular safety concerns in clinical trials 3, 4
• The FDA label includes a warning about monitoring for unusual changes in mood, behavior, or suicidal ideation, although a causal relationship has not been established 1, 2

Contraindications

• Hypersensitivity to prucalopride 1
• Intestinal perforation or obstruction 1
• Severe inflammatory conditions of the intestinal tract such as Crohn's disease, ulcerative colitis, and toxic megacolon/megarectum 2, 1

Clinical Considerations

• Prucalopride may be effective in various types of constipation, including slow transit constipation (STC), obstructed defecation syndrome (ODS), and constipation-predominant irritable bowel syndrome (IBS-C) 5
• A 4-week trial period is reasonable to assess response before deciding on long-term use 5
• Monitor patients for unusual changes in mood or behavior, particularly those with a history of depression 1
• Warn patients about potential initial side effects that typically resolve within days 4

Place in Therapy

• Prucalopride is typically used when first-line treatments (osmotic laxatives, stimulant laxatives) have failed to provide adequate relief 6
• Alternative prescription options for chronic constipation include linaclotide, plecanatide, and lubiprostone, which work through different mechanisms 6
• The American Gastroenterological Association recommends a stepped approach, starting with over-the-counter agents before considering prescription medications like prucalopride 6

Prucalopride offers a unique mechanism of action for treating chronic idiopathic constipation and has demonstrated efficacy in improving bowel function and quality of life in patients who have not responded adequately to laxatives.