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

Abstract

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...

Impact of Prolonged-release Oxycodone/Naloxone on Outcomes Affecting Patients' Daily Functioning in Comparison With Extended-release Tapentadol: A Systematic Review

“…29,33 Long-term evidence from 2 open-label studies of patients who were treated with oxycodone/naloxone for up to 52 weeks revealed relatively good safety and tolerability profiles with oxycodone/naloxone, and the reported AEs were found to be in line with those associated with opioid treatment. 20 In light of this, although withdrawals due to AEs were numerically higher in patients treated with oxycodone/naloxone than with tapentadol, oxycodone/naloxone is tolerable for a longer period of treatment. Oxycodone/naloxone therefore has proven tolerability in the long term and may offer benefits with respect to efficacy compared with tapentadol.…”

“…In an observational study of 588 patients, treatment with oxycodone/naloxone led to statistically significant improvements in both bowel function and QoL compared with patients treated with other strong opioids (Po0.0001 for both outcomes). 20 The benefits of treatment with oxycodone/naloxone were found during a longer period in a 1-year open-label extension study, with a mean (SD) Bowel Function Index score that decreased from 35.6 (27.74) at the start of the extension study to a normal level (Bowel Function Index score r28.8) of 20.6 (24.01) after 1 year. 21,22 Another prescribed opioid analgesic for chronic pain is tapentadol † , although it has only recently become available for use in the treatment of chronic pain after receiving European Medicines Agency and Food and Drug Administration approval for use in this indication in 2011 and is not yet available in every country.…”

“…15 The efficacy of oxycodone/naloxone as an analgesic with improved gastrointestinal tolerability was revealed in a number of clinical studies, including randomized controlled trials (RCTs), an open-label extension study, and an observational study. 16,[18][19][20][21] A randomized, double-blind, placebo-and active-controlled study by Vondrackova et al 16 revealed the efficacy of oxycodone/ naloxone as an analgesic, reporting a significantly longer time to recurrence of pain events in this treatment group compared with placebo (Po0.0003). Furthermore, significant and clinically relevant improvements in Bowel Function Index scores were found in patients treated with oxycodone/naloxone compared with oxycodone in a study by Simpson et al 18 This was further supported by significant improvements in patient-reported measures of constipation, such as the stool and rectal subscales of the Patient Assessment of Constipation Symptoms (PAC-SYM) instrument (Po0.0001) compared with oxycodone alone.…”

Prolonged-release oxycodone/naloxone in opioid-naïve patients – subgroup analysis of a prospective observational study

“…This analysis is based on the previously reported multicenter, prospective, observational study performed from 9 November 2009 through 15 December 2010 by German non-hospitalbased physicians [18]. The study was approved by an ethics committee and registered with the German Federal Institute for Drugs and Medical Devices (BfArM) with study code OXN9505.…”

“…Its analgesic effectiveness and the positive effects on bowel dysfunction under routine clinical practice conditions were demonstrated in a large prospective observational study involving 7836 patients with severe chronic pain of several etiologies [16] and in a retrospective observational study in cancer patients [17]. An additional prospective 4-to 6-week observational study in patients with moderate-to-severe pain of mostly musculoskeletal etiology showed a favorable outcome of OXN PR compared to other strong opioids in terms of pain control, bowel function and QoL measures [18]. In this study, 162 of 588 patients overall were opioid-naïve when treatment with OXN PR or other strong opioids was started.…”