Combined prolonged-release oxycodone and naloxone improves bowel function in patients receiving opioids for moderate-to-severe non-malignant chronic pain: a randomised controlled trial

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

“…After 4 weeks of treatment, patients receiving PR OXN had more complete spontaneous bowel movements per week and a lower laxative intake compared with PR OX patients. Improvements in bowel function were achieved without loss of analgesic efficacy as pain intensity scores were comparable among the groups and consistent for the duration of the study [16].…”

“…Opioid withdrawal was observed in two patients, one for each group. L€ owenstein et al [16] reported more adverse effects in the PR OXN group than the PR OX group. This was attributed to the higher incidence of abdominal pain, as a consequence of an increase in gut motility.…”

“…As the studies in non-cancer pain are limited to a dose range of up to 80/40 mg of PR OXN, further research on higher doses would be recommended [5,6,[14][15][16]. New strengths have been developed recently, which may allow for the use of larger doses.…”

Opioids: a two-faced Janus

“…A subcutaneous formulation of methylnaltrexone has now been approved in Europe, Australia, Chile, Venezuela, Canada and the US for the treatment of opioid-induced constipation, while alvimopan is not FDA-indicated for the treatment of opioid-induced constipation due to safety concerns after a phase III study 65 . A similar effect of ameliorating opioid-induced bowel dysfunction in patients with severe long-term pain has been observed with treatment of oral prolonged-release oxycodone/naloxone, which combines a strong opioid receptor agonist with naloxone, which serves as a peripherally acting opioid receptor antagonist when given as an oral formulation [66][67][68] . However, the strategy of peripheral opioid antagonism may be less useful in chronic pain conditions with a marked inflammatory component, such as rheumatoid arthritis, where opioids have been shown to provide analgesia and anti-inflammatory effects through interaction with peripherally expressed k-opioid receptors 69,70 .…”

Evolving paradigms in the treatment of opioid-induced bowel dysfunction

“…However, when given orally a substantial amount of the drug reaches the [Meissner et al 2000] Significant improvement in bowel function compared to oxycodone as assessed by BFI, number of complete SBMs, and PAC-SYM score. Laxative use reduced [Burness and Keating, 2014;Löwenstein et al 2009;Simpson et al 2008] Only marketed in oral formulation in combination with oxycodone Does not allow for opioid rotation or as add on to existing therapy Methylnaltrexone Peripherally acting, competitive µ-opioid receptor antagonist [Herndon et al 2002] Effective in inducing laxation in opioid treated patients within four hours of administration compared to placebo Only available in subcutaneous formulation and only approved in palliative care in patients with advanced illness Alvimopan Peripherally acting, competitive µ-opioid receptor antagonist [Camilleri, 2005;Schmidt, 2001] Significant increase in weekly SBMs compared to placebo. Improvement in a number of OIBD-related symptoms [Webster et al 2008] Cardiovascular safety concerns Only approved in the USA following partial small or large bowel resection with primary anastomosis in hospitalized patients Naloxegol Peripherally acting, competitive µ-opioid receptor antagonist [Corsetti and Tack, 2015;Eldon et al 2007] Significantly higher response rates for a composite primary endpoint compared with placebo.…”