What is the recommended treatment and dosage for chronic constipation using Prucalopride?

Prucalopride for Chronic Constipation Treatment

Prucalopride is strongly recommended at a dose of 2 mg once daily for adults with chronic idiopathic constipation (CIC) who do not respond to over-the-counter laxatives. 1, 2

Dosage and Administration

• Standard adult dosage: 2 mg once daily 2, 3
• Renal impairment: 1 mg once daily for patients with severe renal impairment (creatinine clearance <30 mL/min) 2, 3
• Can be taken with or without food 2, 3
• No dose adjustment required for elderly patients (≥65 years) 2

Mechanism of Action

Prucalopride is a selective, high-affinity serotonin 5-HT4 receptor agonist that:

• Promotes neurotransmission by enteric neurons
• Stimulates the peristaltic reflex
• Enhances intestinal secretions
• Improves gastrointestinal motility 1, 2

Efficacy

Prucalopride demonstrates significant efficacy in treating chronic constipation:

• Increases complete spontaneous bowel movements (CSBMs) by 0.96 per week compared to placebo 1
• Patients are 2.37 times more likely to achieve ≥3 CSBMs per week compared to placebo 1, 2
• Improves quality of life scores and patient satisfaction with bowel function 1
• Efficacy is generally maintained across different age groups, BMI categories, and in patients with mild renal impairment 4

Treatment Algorithm

1. First-line treatment: Begin with lifestyle modifications and OTC laxatives (e.g., polyethylene glycol)
2. Second-line treatment: If inadequate response after 4-8 weeks, initiate prucalopride 2 mg once daily
3. Evaluate response: Assess efficacy after 4 weeks of treatment 2
4. Continue treatment: If effective and side effects are tolerable, continue treatment 2

Common Side Effects

Most common adverse reactions (≥2%) include:

• Headache
• Abdominal pain
• Nausea
• Diarrhea
• Abdominal distension
• Dizziness
• Vomiting
• Flatulence
• Fatigue 2, 3

Most side effects occur within the first week of treatment and typically resolve within a few days 2.

Important Safety Considerations

Contraindications

• Hypersensitivity to prucalopride
• Intestinal perforation or obstruction
• Severe inflammatory conditions of the intestinal tract (Crohn's disease, ulcerative colitis)
• Toxic megacolon/megarectum 2, 3

Warnings

• Monitor for suicidal ideation: Cases of suicidal thoughts and behavior have been reported, particularly within the first few weeks of treatment
• Discontinue immediately if patient experiences unusual mood changes or suicidal thoughts 2, 3

Clinical Pearls

• Duration of treatment in clinical trials was 4-24 weeks, but the drug label does not provide a specific limit 1
• Prucalopride can be used as a replacement for or as an adjunct to OTC agents 1
• No cardiovascular safety issues have been identified with prucalopride treatment 2
• The 4 mg dose has been studied but shows no additional benefit over the 2 mg dose 1
• Efficacy may be reduced in obese patients and those with moderate renal impairment 4