What is the recommended dosing for Motegrity (prucalopride) for chronic idiopathic constipation?

Motegrity (Prucalopride) Dosing for Chronic Idiopathic Constipation

The recommended dose of Motegrity (prucalopride) is 2 mg once daily for adults with chronic idiopathic constipation, taken with or without food. 1

Standard Dosing Regimen

• Adults with normal renal function should take 2 mg orally once daily as the standard therapeutic dose 2, 1
• The medication can be taken with or without food, providing flexibility for patient convenience 1
• The initial dose range is 1-2 mg daily, with 2 mg being the target therapeutic dose for most patients 2, 3

Dose Adjustments for Special Populations

• Patients with severe renal impairment (creatinine clearance less than 30 mL/min) require dose reduction to 1 mg once daily 1
• No dose adjustment is needed for elderly patients (≥65 years), as efficacy is comparable to younger adults 4
• Patients with mild to moderate renal impairment (CrCL 30-90 mL/min) can use the standard 2 mg dose 4

Dose Titration Strategy

• Titrate based on symptom response and tolerability 2
• The maximum approved dose is 2 mg daily—do not exceed this dose 2, 1
• If patients experience excessive gastrointestinal symptoms (severe cramping, abdominal pain, diarrhea), consider dose reduction rather than increasing 5

Clinical Efficacy Expectations

• Prucalopride increases complete spontaneous bowel movements by approximately 1.37 per week compared to placebo 4
• Response rates show that 23.6-24.7% of patients achieve normal bowel movements with prucalopride versus 11.3% with placebo 6
• The medication may provide additional benefit for abdominal pain beyond improving bowel frequency 2, 3

Common Side Effects and Management

• Headache and diarrhea are the most common adverse events (≥2% incidence), along with abdominal pain, nausea, abdominal distension, dizziness, vomiting, flatulence, and fatigue 1
• Diarrhea may lead to discontinuation in a subset of patients 2, 3
• Most adverse events are mild to moderate in severity 5

Critical Safety Warnings

• Monitor patients for suicidal ideation and behavior, as well as self-injurious ideation and new-onset or worsening depression 1
• Instruct patients to discontinue prucalopride immediately and contact their healthcare provider if they experience unusual changes in mood or behavior, or emerging suicidal thoughts 1
• Prucalopride is contraindicated in patients with hypersensitivity to the drug, intestinal perforation or obstruction, obstructive ileus, or severe inflammatory conditions like Crohn's disease, ulcerative colitis, and toxic megacolon 1

Place in Therapy

• Prucalopride is a serotonin type 4 (5-HT4) receptor agonist that enhances colonic motility 2, 3
• It should be considered for refractory cases when over-the-counter laxatives (particularly polyethylene glycol) have failed to provide adequate relief 7, 3
• The estimated monthly cost is approximately $563, making it more expensive than first-line osmotic laxatives 2

Common Pitfalls to Avoid

• Do not use prucalopride in pregnancy—miscarriages were reported in clinical trials, and women of childbearing age should use effective contraception 6
• Do not exceed the 2 mg daily maximum dose, as higher doses (4 mg) showed no additional benefit over 2 mg in clinical trials 6
• Be cautious about potential reduction in oral contraceptive efficacy—counsel patients accordingly 6