What is the recommended dose of Prucalopride (prucalopride) for constipation?

Recommended Dosage of Prucalopride for Constipation

The recommended dose of prucalopride for chronic idiopathic constipation is 2 mg once daily for adults with normal renal function and 1 mg once daily for patients with severe renal impairment (creatinine clearance <30 mL/min). 1, 2

Dosing Guidelines

• Standard adult dose: 2 mg orally once daily 1
• Dose for severe renal impairment (CrCl <30 mL/min): 1 mg once daily 1, 2
• Can be taken with or without food 2
• No dose adjustment needed based on age - efficacy in elderly patients (≥65 years) is comparable to the overall adult population 1, 3
• No dose adjustment needed based on BMI, although efficacy may be slightly reduced in obese patients 3

Efficacy and Mechanism of Action

• Prucalopride is a selective, high-affinity 5-HT4 receptor agonist that promotes neurotransmission by enteric neurons 1
• It stimulates the peristaltic reflex, intestinal secretions, and GI motility 1
• Clinical trials show it increases complete spontaneous bowel movements (CSBMs) per week (MD 0.96,95% CI 0.64–1.29) compared to placebo 1
• Responder rates (≥3 CSBMs per week) are significantly higher with prucalopride (RR 2.37,95% CI 1.97–2.85) 1
• Onset of action is rapid, with benefits often seen within the first week of treatment 4, 5

Side Effects and Safety Considerations

• Most common adverse events (≥2%): headache, abdominal pain, nausea, diarrhea, abdominal distension, dizziness, vomiting, flatulence, and fatigue 2
• Side effects typically occur during the first week of treatment and resolve within a few days 1
• Diarrhea leading to treatment discontinuation may be higher with prucalopride compared to placebo (RR 3.00,95% CI 1.89–4.78) 1
• Monitor patients for unusual changes in mood, behavior, or suicidal ideation 1, 2
• Cardiovascular adverse events were not more common than placebo in clinical trials 1

Contraindications

• Hypersensitivity to prucalopride 2
• Intestinal perforation or obstruction due to structural or functional disorder of the gut wall 1, 2
• Obstructive ileus 2
• Severe inflammatory conditions of the intestinal tract such as Crohn's disease, ulcerative colitis, and toxic megacolon/megarectum 1, 2

Treatment Algorithm

1. Start with over-the-counter agents (osmotic or stimulant laxatives) as first-line therapy 6
2. If inadequate response to OTC agents, initiate prucalopride at recommended dose based on renal function 1
3. Evaluate response after 4 weeks (clinical trials showed sustained efficacy over 12 weeks) 1, 4
4. Continue treatment if effective; early response (weeks 1-4) predicts long-term response 4
5. If inadequate response or intolerable side effects, consider alternative prescription medications such as linaclotide or plecanatide 6

Clinical Pearls

• Prucalopride has been shown effective in patients with severe chronic constipation who have failed laxative therapy 4, 5
• The drug improves not only bowel movements but also quality of life and patient satisfaction with treatment 7, 4
• Unlike some older 5-HT4 agonists, prucalopride has not shown significant cardiovascular safety issues in clinical trials 1, 7
• The 4 mg dose has been studied but offers no additional benefit over the 2 mg dose for most patients 1, 5
• Warn patients about potential initial side effects (headache, nausea) that typically resolve within days 1