What is the recommended treatment for a patient with chronic idiopathic constipation using Motegrity (prucalopride)?

Motegrity (Prucalopride) for Chronic Idiopathic Constipation

For adults with chronic idiopathic constipation who have failed over-the-counter laxatives, start prucalopride (Motegrity) 2 mg once daily, taken with or without food, as a strong recommendation with moderate certainty of evidence. 1

When to Use Prucalopride

Prucalopride is reserved for patients who have not responded to over-the-counter agents such as polyethylene glycol, fiber supplements, or osmotic laxatives. 1 It functions as a replacement or adjunct to these first-line therapies. 1

The 2023 AGA-ACG guidelines provide a strong recommendation for prucalopride use in this population, with moderate certainty of evidence—placing it on equal footing with linaclotide and plecanatide as prescription options for refractory chronic idiopathic constipation. 1

Dosing and Administration

Standard Dosing

• Adults with normal renal function: 2 mg once daily 2
• Severe renal impairment (CrCl <30 mL/min): 1 mg once daily 2
• Can be taken with or without food 2

Duration of Treatment

• Clinical trials evaluated treatment for 4-24 weeks, but the FDA label does not impose a time limit on use. 1
• Long-term use beyond trial durations is appropriate in clinical practice. 1

Mechanism and Efficacy

Prucalopride is a highly selective serotonin-4 (5-HT4) receptor agonist that enhances colonic motility and accelerates transit. 1, 2, 3

In network meta-analysis comparing all available agents for chronic idiopathic constipation, prucalopride 2 mg once daily ranked first at 12 weeks for achieving three or more complete spontaneous bowel movements per week (RR 0.82,95% CI 0.78-0.86). 4 This positions it as the most efficacious prescription agent for patients with refractory constipation who have previously failed laxatives. 4

Side Effects and Safety Monitoring

Common Adverse Effects (≥2%)

• Headache 1, 2
• Abdominal pain 1, 2
• Nausea 1, 2
• Diarrhea 1, 2

These side effects may lead to discontinuation in a subset of patients. 1

Critical Safety Warning: Suicidal Ideation

Monitor all patients for new-onset or worsening depression, suicidal thoughts, or self-injurious ideation, particularly within the first few weeks of treatment. 2 While a causal relationship has not been definitively established, suicides, suicide attempts, and suicidal ideation have been reported in clinical trials and postmarketing surveillance. 2

Instruct patients to discontinue prucalopride immediately and contact their healthcare provider if they experience unusual mood changes or suicidal thoughts. 2 Counsel patients, caregivers, and family members about this risk before initiating therapy. 2

Contraindications

Prucalopride is absolutely contraindicated in: 2

• Hypersensitivity to prucalopride (including dyspnea, rash, pruritus, urticaria, facial edema) 2
• Intestinal perforation or obstruction 2
• Obstructive ileus 2
• Severe inflammatory bowel disease (Crohn's disease, ulcerative colitis) 2
• Toxic megacolon or megarectum 2

Comparative Positioning

Prucalopride is one of three prescription agents with strong recommendations and moderate certainty of evidence for chronic idiopathic constipation, alongside linaclotide and plecanatide. 1

Key differentiators:

• Prucalopride may provide additional benefit for abdominal pain. 1
• Monthly cost is approximately $563, compared to $523 for linaclotide and $526 for plecanatide. 1
• Prucalopride ranked first in long-term efficacy (12 weeks) in network meta-analysis, particularly in patients who failed laxatives. 4

Lubiprostone has only a conditional recommendation with low certainty of evidence, making prucalopride, linaclotide, or plecanatide preferred choices when escalating from over-the-counter agents. 1

Clinical Pitfalls to Avoid

• Do not use prucalopride as first-line therapy. Always trial polyethylene glycol 17 grams daily first, as it has strong evidence, excellent safety, and costs only $10-45 per month. 5, 6
• Do not overlook the psychiatric safety warning. Failure to counsel patients and monitor for suicidal ideation is a critical oversight. 2
• Do not use in patients with structural bowel disorders or severe inflammatory bowel disease. This is an absolute contraindication. 2
• Reduce dose to 1 mg daily in severe renal impairment. Failure to adjust dosing increases risk of adverse effects. 2