What is the highest recommended dose of prucalopride (Resolor) for an adult patient with chronic constipation and potentially impaired renal function?

Prucalopride Maximum Dose

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

Standard Dosing for Adults

• The maximum dose is 2 mg orally once daily for adults with normal renal function or mild-to-moderate renal impairment. 1, 2
• This dose can be taken with or without food, as food does not affect efficacy. 3, 2
• The initial recommended dose is 1-2 mg daily, titrated per symptom response, with 2 mg daily being the maximum. 1, 4

Dose Adjustment for Renal Impairment

For patients with severe renal impairment (CrCl <30 mL/min), the dose must be reduced to 1 mg once daily. 4, 2

• This reduction is necessary because drug exposure increases 2.38-fold in severe renal impairment, which could lead to excessive systemic side effects. 4
• No dose adjustment is needed for mild (CrCl 60-89 mL/min) or moderate (CrCl 30-59 mL/min) renal impairment. 5
• The dose reduction is a pharmacokinetic precaution to prevent excessive drug levels, not to protect the kidneys from direct damage. 4

Higher Doses Are Not Recommended

• The 4 mg dose has been studied but offers no additional clinical benefit over the 2 mg dose. 4, 6
• Clinical trials demonstrated that 4 mg once daily provided no incremental improvement in bowel movement frequency or symptom relief compared to 2 mg. 6, 7
• The 4 mg dose showed the largest effect during the first week in elderly patients, but this did not translate to sustained superiority over lower doses. 8

Age-Related Considerations

• No dose adjustment is needed based on age alone—efficacy in elderly patients (≥65 years) is comparable to younger adults. 4, 3
• Elderly patients can safely receive the standard 2 mg daily dose (or 1 mg if severe renal impairment is present). 8

Clinical Context

• The 2 mg maximum dose is based on the balance between efficacy and tolerability, as higher doses increase the risk of diarrhea leading to discontinuation (RR 3.00 compared to placebo). 4
• Most adverse events (headache, nausea, diarrhea) occur during the first week and typically resolve within days. 4, 9
• Prucalopride has demonstrated cardiovascular safety at doses up to 20 mg daily (10-fold higher than therapeutic doses) in healthy volunteers, with no clinically relevant QT prolongation. 6

Common Pitfalls to Avoid

• Do not exceed 2 mg daily in adults with normal renal function—there is no evidence of additional benefit and it may increase side effects. 6, 7
• Always assess baseline creatinine clearance before initiating therapy to determine appropriate dosing. 4
• Do not assume elderly patients need lower doses based on age alone; renal function is the determining factor. 4, 3, 8