Long-term efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of non-cancer chronic pain

Abstract

Objective:The aim of this study was to assess safety and efficacy of fixed combination oxycodone prolonged release (PR)/naloxone PR in terms of both analgesia and improving opioid-induced bowel dysfunction (OIBD) and associated symptoms, such as opioid-induced constipation (OIC), in adults with chronic non-cancer pain.Study design:These were open-label extension studies in which patients who had previously completed a 12-week, double-blind study received oxycodone PR/naloxone PR for up to 52 weeks. The analgesia study assessed pain using the modified Brief Pain Inventory-Short Form (BPI-SF). The bowel function study assessed improvements in constipation using the Bowel Function Index (BFI).Results:At open-label baseline in the analgesia study (n = 379), mean score [± standard deviation (SD)] for the BPI-SF item ‘average pain over the last 24 h’ was 3.9 ± 1.52, and this remained low at 6 months (3.7 ± 1.59) and 12 months (3.8 ± 1.72). Mean scores for BPI-SF item ‘sleep interference’, and the BPI-SF ‘pain’ and ‘interference with activities’ subscales also remained low throughout the 52-week study. In the bowel function study (n = 258), mean BFI score (± SD) decreased from 35.6 ± 27.74 at the start of the extension study to 20.6 ± 24.01 after 12 months of treatment with oxycodone PR/naloxone PR. Pain scores also remained low and stable during this study. Adverse events in both extension phases were consistent with those associated with opioid therapy; no additional safety concerns were observed.Conclusion:Results from these two open-label extension studies demonstrate the long-term efficacy and tolerability of fixed combination oxycodone PR/naloxone PR in the treatment of chronic pain. Patients experienced clinically relevant improvements in OIBD while receiving effective analgesic therapy.

Opioid-induced constipation: advances and clinical guidance

“…The fixed dose ratio proved to be safer in the long term, with only mild to moderate adverse events and only 13% incidence of severe adverse events [Sandner-Kiesling et al 2010]. The combination of oxycodone and naloxone at a 2:1 ratio, with a maximum dose of 40 mg of naloxone, proved to be more efficacious in the treatment of OIC [Meissner et al 2009]; however, due to induction of opioid withdrawal symptoms, the maximum dosing strengths in 2:1 oral combination therapy approved by the FDA is oxycodone 40 mg and naloxone 20 mg (http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/ 205777lbl.pdf).…”

“…The most common adverse effects of the combination of oxycodone and naloxone are nausea, vomiting, headache, constipation and diarrhea [Vondrackova et al 2008;Sandner-Kiesling et al 2010]. The fixed dose ratio proved to be safer in the long term, with only mild to moderate adverse events and only 13% incidence of severe adverse events [Sandner-Kiesling et al 2010].…”

Combined oral prolonged-release oxycodone and naloxone in chronic pain management

“…Patients experienced clinically relevant improvements in OIC, while receiving effective analgesic therapy [21]. Limited data are available in cancer pain.…”

Patient preference with respect to QoL and reduction in opioid‐induced constipation ( OIC ) after treatment with prolonged‐release ( PR ) oxycodone/naloxone compared with previous analgesic therapy [ PREFER study]

“…This is an expected increase, since all patients started with a daily oxycodone dosage of 10 or 20 mg and oxycodone PR/naloxone PR was titrated within the study until an effective analgesic dose was reached. This is also reflected by rescue analgesic medication use, which decreases over time (26,27). Although a statistical improvement in pain NRS score was shown in the study, pain scores remained relatively high during the 3-week core study.…”