Efficacy and Safety of Prucalopride in Patients with Chronic Noncancer Pain Suffering from Opioid-Induced Constipation

Abstract

BackgroundOpioid-induced constipation (OIC) has negative effects on quality of life (QOL). Prucalopride is a new, selective 5-HT4 agonist and enterokinetic with strong clinical data in chronic constipation. This study investigated the efficacy, safety, and tolerability of prucalopride in patients with noncancer pain and OIC.MethodsA phase II, double-blind, placebo-controlled study of 196 patients randomized to placebo (n = 66), prucalopride 2 mg (n = 66) or 4 mg (n = 64), for 4 weeks, was carried out. The primary endpoint was the proportion of patients with increase from baseline of ≥1 spontaneous complete bowel movement (SCBM)/week. Secondary endpoints [proportion of patients with ≥3 SCBM/week, weekly frequency of (SC)BM, severity of constipation, and efficacy of treatment], adverse events (AEs), and safety parameters were also monitored.ResultsMore patients had an increase from baseline of ≥1 SCBM per week (weeks 1–4) in the prucalopride groups [35.9% (2 mg) and 40.3% (4 mg)] versus placebo (23.4%), reaching statistical significance in week 1. Over weeks 1–4, more patients in the prucalopride groups achieved an average of ≥3 SBM per week versus placebo (60.7% and 69.0% versus 43.3%), reaching significance at week 1. Prucalopride 4 mg significantly improved patient-rated severity of constipation and effectiveness of treatment versus placebo. Patient Assessment of Constipation-Symptom (PAC-SYM) total scores and Patient Assessment of Constipation-Quality of Life (PAC-QOL) total and satisfaction subscale scores were improved. The most common AEs were abdominal pain and nausea. There were no clinically relevant differences between groups in vital signs, laboratory measures or electrocardiogram parameters.ConclusionIn this population with OIC, prucalopride improved bowel function and was safe and well tolerated.

The Effect of DA-9701 in Opioid-induced Bowel Dysfunction of Guinea Pig

“…8,9 Several prokinetic agents have been developed recently, yet their use is restricted due to serious side ef- fects and failure to confirm their efficacy. On the other hand Sloots et al 22 studied the efficacy and safety of prucalopride in chronic constipation from opioid induced constipation, and they suggested improved bowel movement frequency. Hence, there is an increasing challenge to develop safer and more effective therapeutic agents for the treatment of OIBD.…”

Use of Prucalopride for Chronic Constipation: A Systematic Review and Meta-analysis of Published Randomized, Controlled Trials

“…Sixteen randomized, controlled trials [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] on 3943 patients were retrieved from the search of standard medical electronic databases. The characteristics, salient features and treatment protocols adopted in the included randomized, controlled trials are given in the Table. All trials were adequately randomized using either computer generated sequential pattern or other reliable random pattern methods.…”

Management of opioid-induced constipation

“…Among patients with chronic non-cancer pain suffering from OIC, 69% of patients receiving 4mg of prucalopride passed ≥3 spontaneous bowel motions per week (compared to 43% of patients receiving placebo) after 4 weeks treatment (Sloots et al, 2010). However, it is not approved by the FDA and in the United Kingdom is only approved for the treatment of refractory constipation.…”