A randomised controlled trial with prolonged‐release oral oxycodone and naloxone to prevent and reverse opioid‐induced constipation

ABSTRACT Background: Opioid‐induced constipation can have a major negative impact on patients’ quality of life. This randomised, double‐blinded study evaluated the analgesic efficacy of prolonged‐release (PR) oral oxycodone when co‐administered with PR oral naloxone, and its impact on opioid‐induced constipation in patients with severe chronic pain. Another objective was to identify the optimal dose ratio of oxycodone and naloxone. Methods: A total of 202 patients with chronic pain (mainly non‐cancer related, 2.5% of patients had cancer‐related pain) under stable oral oxycodone therapy (40, 60 or 80mg/day) were randomised to receive 10, 20, 40mg/day naloxone or placebo. After a 4‐week maintenance phase, patients received oxycodone only for 2 weeks. Pain intensity was evaluated using a numerical analogue scale and bowel function was assessed using the bowel function index. Results: No loss of analgesic efficacy with naloxone was observed. Mean pain intensity scores on randomisation were comparable for placebo, 10mg, 20mg and 40mg naloxone dose, and remained unchanged during treatment. Bowel function improved with increasing naloxone dose. Naloxone 20mg and 40mg significantly improved bowel function at the end of the maintenance phase compared with placebo ( p <0.05). Overall, the combination was well tolerated, with no unexpected adverse events. There was a trend towards an increased incidence of diarrhoea with higher doses of naloxone. The 2:1 oxycodone/naloxone ratio was identified as the most suitable for further development. Conclusion: Co‐administration of PR oral naloxone and PR oral oxycodone is associated with a significant improvement in bowel function compared with PR oral oxycodone alone, with no reduction in the analgesic efficacy of oxycodone.