Effects of prolonged-release oxycodone/naloxone on pain control, bowel function and quality of life: A prospective observational study.

Background and aim Strong opioids including oxycodone are amongst the most effective analgesics to combat moderate to severe pain of various aetiologies, but opioid-induced bowel dysfunction (OIBD) represents a relevant problem. The rationale for development of a prolonged-release (PR) fixed combination of oxycodone and naloxone was to counteract OIBD. Due to its negligible oral bioavailability, the μ-opioid receptor antagonist naloxone is able to selectively displace opioids from local μ-receptors in the gastrointestinal tract without affecting central opioid binding sites. Pivotal trials of PR oxycodone/naloxone not only demonstrated improved bowel function but also equivalent analgesic efficacy compared to PR oxycodone alone. Controlled clinical trials comparing PR oxycodone/naloxone with strong opioids other than oxycodone are not available. The present study is the first data set aimed at comparing pain control, bowel function, and quality of life (QoL) in patients newly treated with or switched to PR oxycodone/naloxone or other strong opioids during routine clinical practice. Methods In this three-arm, prospective observational study, 588 patients with moderate to severe pain of varying aetiologies received either PR oxycodone/naloxone (OXN group and OXN 40/20 group with indicated use of the 40 mg/20 mg dose strength at baseline) or other strong opioids (control group), dosed according to pain severity, for 4-6 weeks. Data documented include pain intensity (NRS), bowel function (Bowel Function Index, BFI), pain-related functional impairment (BPI-SF), QoL (EuroQol EQ-5D-3L), and a global assessment of treatment. Results Patients receiving PR oxycodone/naloxone experienced a clinically important reduction in pain intensity and pain-related functional impairment of approximately 40%. The reductions of pain intensity (-2.9 ± 2.3) and pain-related functional impairment (-2.4 ± 2.3) in the OXN group were significantly more pronounced than in the control group (-2.1 ± 2.1 and -1.8 ± 1.7). In the control group, mean reductions in pain intensity did not reach the threshold of ≥30% for at least moderate clinically important differences, although patients were prescribed higher doses of morphine equivalents than OXN group patients. Improvements in bowel function (OXN: -16.0 ± 27.6; control: 3.1 ± 24.4) and QoL (OXN: 20.8 ± 24.2; control: 13.2 ± 23.1) were also significantly more pronounced in the OXN group, with BFI scores reduced to a level that reflects normal bowel function. Results for the OXN 40/20 group receiving higher doses of PR oxycodone/naloxone were in line with those for the OXN group. In the control group, more frequent gastrointestinal adverse events and less favourable ratings of tolerability resulted in a higher rate of treatment discontinuations due to adverse events. Conclusions In patients receiving PR oxycodone/naloxone, more favourable outcomes compared with other strong opioids regarding pain control, bowel function, and QoL were observed. Implications The present findings underline the value of PR oxycodone/naloxone in the management of patients with moderate to severe chronic pain. The data set further adds to our understanding of the benefits and risks of opioid treatment in routine clinical practice.