What is the recommended dosage and timing of prucalopride (Resolor) for treating constipation?

Prucalopride Dosing for Chronic Idiopathic Constipation

The standard dose of prucalopride is 2 mg once daily for adults with normal renal function, taken at any time of day with or without food. 1, 2

Dosing by Patient Population

Standard Adult Dosing

• 2 mg orally once daily is the recommended dose for adults with chronic idiopathic constipation 1, 2
• Can be taken with or without food 2
• No specific timing requirement during the day 2

Renal Impairment

• Reduce to 1 mg once daily in patients with severe renal impairment (creatinine clearance <30 mL/min) 1, 3, 2
• No dose adjustment needed for mild to moderate renal impairment 2

Elderly Patients (≥65 years)

• Use standard 2 mg once daily dose - no age-based adjustment required 1, 3
• Efficacy in elderly patients is comparable to the overall adult population 1

Clinical Efficacy and Onset

• Response typically begins within the first week of treatment 1, 4
• Significant differences from placebo are evident in week 1 and sustained thereafter 4
• Early response (weeks 1-4) predicts ultimate response over time 4
• The 4 mg dose offers no additional benefit over 2 mg and is not recommended 3, 5

Important Safety Considerations

Common Side Effects (Timing and Management)

• Headache, nausea, abdominal pain, and diarrhea are the most frequent adverse events 1, 2
• These side effects occur primarily during the first week of treatment and typically resolve within a few days 1, 3
• Most adverse events are transient and mild to moderate in severity 5

Critical Safety Warnings

• Monitor for unusual changes in mood, behavior, or suicidal ideation - the FDA label includes a warning about potential psychiatric effects 1, 2
• Instruct patients to discontinue immediately and contact their healthcare provider if they experience emerging suicidal thoughts or unusual mood changes 2
• However, the causal relationship between prucalopride and suicide risk remains unclear 1

Cardiovascular Safety

• No increased cardiovascular adverse events compared to placebo in clinical trials 1, 3
• Unlike older 5-HT4 agonists, prucalopride has not shown significant cardiovascular safety issues 3
• QT interval prolongation incidence is low and similar to placebo 5

Absolute Contraindications

Prucalopride is contraindicated in patients with: 1, 2

• Intestinal perforation or obstruction
• Crohn's disease
• Ulcerative colitis
• Toxic megacolon/megarectum

Treatment Algorithm

1. Initiate at 2 mg once daily (or 1 mg if CrCl <30 mL/min) 1, 2
2. Warn patients about potential first-week side effects that typically resolve within days 1, 3
3. Evaluate response after 4 weeks - clinical trials demonstrated sustained efficacy over 12 weeks 3
4. Continue long-term if effective - satisfaction with treatment maintained up to 24 months 5

Common Pitfalls to Avoid

• Do not increase to 4 mg thinking it will improve efficacy - studies show no additional benefit 3, 5
• Do not discontinue prematurely for mild GI side effects in the first week - these typically resolve spontaneously 1
• Do not forget renal dose adjustment - failure to reduce dose in severe renal impairment may increase adverse events 1, 2
• Do not use in inflammatory bowel disease - this is an absolute contraindication 1, 2