What is Resolor (prucalopride) and its dosing, indications, contraindications, and adverse effects for chronic idiopathic constipation in adults?

What is Resolor (Prucalopride)?

Resolor (prucalopride) is a highly selective serotonin 5-HT4 receptor agonist approved for treating chronic idiopathic constipation in adults who have not responded adequately to over-the-counter laxatives. 1, 2

Mechanism of Action

• Prucalopride selectively stimulates 5-HT4 receptors in the enteric nervous system, promoting peristaltic reflex, intestinal secretions, and gastrointestinal motility without interacting with cardiac hERG potassium channels. 2, 3
• This high selectivity distinguishes it from older 5-HT4 agonists (cisapride, tegaserod) that were withdrawn due to cardiac safety concerns—prucalopride does not cause QT prolongation or increase cardiovascular adverse events. 2, 3
• The drug directly stimulates colonic motility, differentiating it from osmotic agents and chloride secretagogues. 3

Indications

• FDA-approved for chronic idiopathic constipation (CIC) in adults. 1
• Recommended by the American Gastroenterological Association and American College of Gastroenterology (moderate certainty evidence) for adults with CIC who do not respond to over-the-counter agents. 2
• Can be used as replacement for or adjunct to OTC laxatives. 2
• Note: The AGA makes no recommendation for prucalopride in opioid-induced constipation due to insufficient evidence. 4

Dosing

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
• Elderly patients (≥65 years): No dose adjustment needed—efficacy is comparable to younger adults 2, 5
• Can be taken with or without food 1, 5

Treatment Duration

• Assess response after 4 weeks minimum based on increase in weekly bowel movements and patient satisfaction. 2, 6
• No time limit specified by FDA—continue as long as clinical benefit persists and medication is tolerated. 6
• Clinical trials studied 4-24 weeks, with five pivotal 12-week randomized controlled trials forming the primary evidence base. 6

Clinical Efficacy

• Increases complete spontaneous bowel movements (CSBMs) per week by 0.96 (95% CI 0.64–1.29) compared to placebo. 2
• Responder rates (≥3 CSBMs per week) are significantly higher: RR 2.37 (95% CI 1.97–2.85). 2
• Improves stool consistency, straining, and overall patient satisfaction. 2
• Onset of action typically occurs within the first week. 5

Contraindications

Prucalopride is contraindicated in patients with: 1

• History of hypersensitivity to prucalopride (reactions include dyspnea, rash, pruritus, urticaria, facial edema) 1
• Intestinal perforation or obstruction due to structural or functional disorder of the gut wall 1, 2
• Obstructive ileus 1
• Severe inflammatory conditions: Crohn's disease, ulcerative colitis, toxic megacolon/megarectum 1, 2

Adverse Effects

Common Adverse Events

• Most frequent: headache, diarrhea, nausea, and abdominal pain 1, 7
• Side effects typically occur during the first week and resolve within a few days. 2, 5
• Diarrhea leading to treatment discontinuation may be higher with prucalopride (RR 3.00,95% CI 1.89–4.78) compared to placebo. 2

Serious Safety Concerns

• Suicidal ideation and behavior: Monitor all patients for new onset or worsening depression or emergence of suicidal thoughts. 1
• Postmarketing cases of suicidal ideation, self-injurious ideation, and worsening depression reported within first few weeks. 1
• Instruct patients to discontinue immediately and contact healthcare provider if these symptoms occur. 1
• Cardiovascular adverse events were not more common than placebo in clinical trials—no cardiac safety issues identified. 2, 3

Clinical Pearls and Pitfalls

Key Considerations

• Unlike dopamine antagonists (metoclopramide), prucalopride does not cause extrapyramidal side effects or tardive dyskinesia. 2
• No specific renal monitoring required beyond baseline creatinine clearance assessment for dose determination. 2
• Taking at the same time daily may improve adherence, though food timing is irrelevant. 5

Common Pitfalls to Avoid

• Do not discontinue prematurely before 4 weeks unless intolerable side effects occur—initial GI symptoms typically resolve. 6
• Do not assume treatment must be time-limited based on trial durations—medication can be continued as long as clinically beneficial. 6
• Warn patients about potential initial side effects (headache, nausea) that typically resolve within days to prevent premature discontinuation. 2

Treatment Algorithm

1. Confirm diagnosis of chronic idiopathic constipation and inadequate response to OTC agents. 2
2. Assess renal function (creatinine clearance) to determine appropriate dose. 1, 2
3. Initiate prucalopride 2 mg once daily (or 1 mg if CrCl <30 mL/min). 1, 2
4. Counsel patient about expected initial side effects and psychiatric monitoring. 1, 2
5. Evaluate response at 4 weeks minimum using bowel movement frequency and patient satisfaction. 2, 6
6. Continue treatment indefinitely if beneficial and tolerated. 6