Opioid-Induced Constipation Relief From Fixed-Ratio Combination Prolonged-Release Oxycodone/Naloxone Compared With Oxycodone and Morphine for Chronic Nonmalignant Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Context: Opioid-induced constipation (OIC) is one of the most frequent and severe adverse events (AEs) after treatment with opioids. Recent studies have indicated that fixed-ratio combination prolonged-release oxycodone/naloxone (OXN PR) could decrease OIC with similar pain relief compared with other opioids.

Objectives: We systematically reviewed (PROSPERO registration numbers: CRD42016036244) the constipation relief of OXN PR compared with other opioids regardless of formulation, prolonged release, or extended release used for the relief of chronic pain.

Methods: Relevant studies were identified by searching PubMed, EMBASE, Web of Science, and the Cochrane library from inception to May 2016, with an update to December 2016. We quantitatively analyzed OIC (assessed by bowel function index [BFI]), pain intensity, and AEs.

Results: A total of 167 articles were identified from the databases. Finally seven studies with 3217 patients were included in our meta-analysis, including 1322 patients in OXN PR treatment groups and 1885 patients in prolonged-release oxycodone (OXY PR) or prolonged-release morphine (MOR PR) control group. The relative risk (RR) of OIC was decreased in OXN PR (RR 0.52, 95% CI 0.44; 0.62). Whether BFI was better or worse at baseline, the mean difference (MD) of BFI -17.48 95% CI -21.60; -13.36) was better after treatment with OXN PR with clinical importance at the end of intervention; moreover, the BFI of the OXN PR-treated group was closer to normal BFI scores. However, clinical BFI change from baseline to the end measurement only existed in patients when the baseline BFI was high (mean [SDs] 61.0 [23.39]-67.40 [19.51]), and the MD of the BFI was -15.96 (95% CI -25.56; -15.48). The RR of AEs was also smaller (RR 0.80; 95% CI 0.69-0.93), but the severity or duration of AEs was not reported. Pain intensity was also significantly decreased in the OXN PR treatment groups (MD -3.84, 95% CI -7.14; -0.55), although there was no clinically meaningful difference.

Conclusion: For people with chronic pain, treatment with OXN PR decreases the incidence of OIC and provides intermediate-term bowel function improvement with clinical importance; in addition, pain relief is not weakened. The OIC after treatment with OXN PR for cancer-related pain and over the long term remains unknown.

Keywords: Constipation; chronic nonmalignant pain; naloxone; oxycodone; systematic review and meta-analysis.