What is the recommended treatment protocol for chronic constipation using Prucalopride?

Prucalopride for Chronic Idiopathic Constipation

For adults with chronic idiopathic constipation, prescribe prucalopride 2 mg once daily (or 1 mg once daily if creatinine clearance is <30 mL/min), which effectively increases bowel movements and improves quality of life with moderate-to-high quality evidence. 1, 2

Dosing Protocol

Standard dosing:

• Adults with normal renal function: 2 mg orally once daily 1, 2
• 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 for elderly patients (≥65 years)—efficacy is comparable to younger adults 1, 3

Mechanism and Efficacy

Prucalopride is a selective, high-affinity serotonin 5-HT4 receptor agonist that induces and increases the amplitude of colonic high-amplitude propagated contractions, which propel colonic contents forward. 1, 3

Clinical outcomes with high-to-moderate certainty evidence:

• Increases complete spontaneous bowel movements (CSBMs) by approximately 1 per week compared to placebo (MD 0.96,95% CI 0.64–1.29) 3
• Responder rate (≥3 CSBMs per week): 2.37 times higher than placebo (RR 2.37,95% CI 1.97–2.85) 3
• Improves constipation symptoms, abdominal symptoms, quality of life (PAC-QOL scores 0.32 points lower, 95% CI 0.41–0.23 lower), and patient satisfaction 1
• Global relief rates are doubled compared to placebo (RR 2.09,95% CI 0.15–3.0) 1

Treatment Duration and Monitoring

Assess response after 4 weeks of treatment to determine if the patient is benefiting from therapy. 3, 4

There is no time limit for treatment duration—continue as long as clinical benefit persists and the medication is tolerated. 4, 2 The FDA label explicitly states no maximum duration. 4 Clinical trials studied prucalopride for 4-24 weeks, with five pivotal 12-week trials forming the evidence base, but long-term use is supported when clinically beneficial. 4

Side Effects and Safety

Most adverse events occur during the first week and typically resolve within a few days: 1

• Headache (most common) 1
• Abdominal pain 1
• Nausea 1
• Diarrhea (RR 3.00 vs placebo, 95% CI 1.89–4.78 for treatment discontinuation) 1, 3

Warn patients that initial gastrointestinal symptoms usually resolve quickly—do not discontinue prematurely before 4 weeks unless side effects are intolerable. 4

Only 5% of patients discontinued prucalopride due to side effects in clinical trials. 1 Cardiovascular adverse events were not more common than placebo. 1, 3

Critical Safety Warning: Suicidal Ideation

Monitor all patients for new onset or worsening depression, suicidal thoughts, or unusual changes in mood or behavior. 2 In a safety database of 4,476 subjects, 4 individuals attempted suicide and 2 completed suicide (both had discontinued prucalopride >1 month before the event). 1 A causal association has not been established, but the FDA label requires counseling patients and caregivers to be alert to these symptoms. 2

Instruct patients to discontinue prucalopride immediately and contact their healthcare provider if they experience unusual mood changes, depression, or suicidal thoughts. 2

Absolute Contraindications

Prucalopride is contraindicated in patients with: 1, 2

• Intestinal perforation or obstruction due to structural or functional disorder
• Obstructive ileus
• Severe inflammatory conditions: Crohn's disease, ulcerative colitis, toxic megacolon/megarectum
• History of hypersensitivity to prucalopride (dyspnea, rash, pruritus, urticaria, facial edema)

Pregnancy and Lactation

No drug-associated risks of miscarriage, major birth defects, or adverse maternal or fetal outcomes have been identified. 1

Common Pitfalls to Avoid

• Do not discontinue before 4 weeks unless intolerable side effects occur—initial symptoms (headache, nausea, diarrhea) typically resolve within days 4
• Do not assume treatment must be time-limited—prucalopride can be continued indefinitely as long as clinically beneficial 4
• Do not fail to counsel about psychiatric symptoms—this is an FDA-mandated warning despite unclear causality 2
• Do not use in patients with inflammatory bowel disease or intestinal obstruction—these are absolute contraindications 1, 2