Oral prolonged-release Oxycodone-Naloxone: analgesic response, safety profile, and factors influencing the response in advanced cancer patients.

BACKGROUND: Oxycodone-Naloxone (OXN) aims to reduce opioid-related constipation while being successfully analgesic. METHODS: We evaluated the analgesic response, prevalence, and severity of side effects in 176 cancer patients with moderate to severe pain and treated with OXN. Patients were followed for 28 days and evaluated every seven. Pain intensity, changes of therapy, and adverse drug reactions were recorded at each visit. The primary efficacy endpoint was the proportion of responders (≥30% reduction of pain intensity from baseline to final) and final average pain score ≤4 on a 0-10 scale. RESULTS: Average and worst pain intensity, and breakthrough pain (BTP) prevalence decreased over time and 81.3% of patients were responders. The starting daily dose of OXN was raised from 25.1±13.0 mg to 44.1±29.9 mg, and dose escalation >5%/day was observed in 19.4% of patients; 40.8-46.2% and 11.0-17.0% experienced any and severe grade of constipation during the follow-up visit, respectively. Digestive system tumor, thyroid endocrinopathies, psychological irritability, and BTP increased the risk of analgesic non-response. CONCLUSIONS: OXN had strong analgesic effect in moderate to severe cancer pain patients: the safety profile is in line with the common adverse effects of opioids and severe constipation was uncommon. This article is protected by copyright. All rights reserved.

Oral oxycodone/naloxone for pain control in cirrhosis: Observational study in patients with symptomatic metastatic hepatocellular carcinoma.

BACKGROUND & AIMS: Pain management in cirrhosis is a clinical challenge. Most analgesics are metabolized in the liver and cirrhosis may deeply alter their concentration, favouring the appearance of side effects. We aimed to assess the efficacy and safety of oral prolonged-release association of oxycodone/naloxone tablets (OXN) in the treatment of moderate/severe cancer pain in cirrhotic patients with metastatic hepatocellular carcinoma (HCC). METHODS: We enrolled n = 32 HCC patients with moderate/severe cancer pain unresponsive to paracetamol alone or associated with codeine or tramadol. All patients received an initial OXN dose of 5 mg bid to be gradually increased in case of insufficient analgesia. At baseline and follow-up visits, we evaluated: pain intensity (using the Numerical Rating Scale, NRS), patients' autonomy in daily activities (Barthel Functioning Index); bowel dysfunction (Bowel Function Index, BFI), signs of hepatic encephalopathy (HE) and other opioid-induced side effects. RESULTS: No clinically significant adverse effects were reported (median follow-up 122 days). No significant worsening of the BFI score was noted and no cases of HE were detected. Two patients (6.3%) discontinued treatment before T14 because of mild nausea and dizziness. The remaining n = 30 patients were assessed for efficacy. Treatment led to a significant reduction in the mean of pain scores both at T14 (-37.1 ± 16.3%, P < .001) and at T28 (-55.6 ± 21.5%, P < .001); Barthel scores showed gradual and significant increase from T0 (81.6 ± 13.0) to T14 (86.5 ± 11.4, P = .001) and to T28 (88.3 ± 13.6, P = .009). CONCLUSIONS: OXN may be considered a safe and effective option in the fragile population of cirrhotic patients.

Managing Severe Cancer Pain with Oxycodone/Naloxone Treatment: A Literature Review Update.

Severe cancer pain substantially affects patients' quality of life, increasing the burden of the disease and reducing the disability-adjusted life years. Although opioid analgesics are effective, they may induce opioid-induced bowel dysfunction (OIBD). Oxycodone/naloxone combination therapy has emerged as a promising approach to mitigate opioid-induced constipation (OIC) while providing effective pain relief. This review provides an updated analysis of the literature of the last decade regarding the use of oxycodone/naloxone in the management of severe cancer pain. Through a comprehensive search of databases, studies focusing on the efficacy, safety, and patient experience of oxycodone/naloxone's prolonged release in severe cancer pain management were identified. Furthermore, the literature discusses the mechanism of action of naloxone in mitigating OIC without compromising opioid analgesia. Overall, the evidence suggests that oxycodone/naloxone combination therapy offers a valuable option for effectively managing severe cancer pain while minimizing opioid-induced constipation, thereby improving patients' quality of life. However, further research is needed to optimize dosing regimens, evaluate long-term safety, and assess patient outcomes in diverse cancer populations.

Health-Related Quality of Life in Chronic Pain Treated With Tapentadol Versus Oxycodone/Naloxone and Its Determinants: A Real-World, Single-Center Retrospective Cohort Study in Spain.

OBJECTIVES: A substantial proportion of patients with chronic noncancer pain (CNCP) are treated with tapentadol (TAP) or oxycodone/naloxone (OXN) to improve their perceived physical and mental health over time. METHODS: A cross-sectional study was conducted in 135 CNCP outpatients with usual prescribing (TAP: n = 58, OXN: n = 77) at a tertiary-care Spanish Hospital to compare health-related quality-of-life (HRQoL) records. Health utility was derived from the EQ-5D-3L. Regression models were performed to search for other HRQoL determinants. Pain intensity, relief, analgesic prescription, adverse events, inpatient stays, emergency department visits, and change to painkiller prescriptions were registered from electronic records. RESULTS: Health utility (0.43 ± 0.24 scores, from -0.654 to 1) was similar for both opioids, although TAP showed a significantly low daily opioid dose requirement, neuromodulators use, and constipation side effect compared with OXN. After multivariable adjustment, the significant predictors of impaired HRQoL were pain intensity (ß = -0.227, 95% CI -0-035 to -0.005), number of adverse events (ß = -0.201, 95% CI -0.024 to -0.004), and opioid daily dose (ß = -0.175, 95% CI -0.097 to -0.012). Male sex (ß = -0.044) and pain relief (ß = 0.158) should be taken into account for future studies. CONCLUSIONS: HRQoL was similar for TAP and OXN in real-world patients with CNCP, albeit with a TAP opioid-sparing effect. More work is needed to explore HRQoL determinants in relation to long-term opioid use in CNCP.

Pain therapy with oxycodone/naloxone prolonged-release combination: case report.

Pain afflicts patients suffering from many chronic diseases and is present in 80% of cases of patients with advanced cancer who suffer from persistent pain. The aim of the pain treatment is to achieve the maximum analgesic effect while minimizing side effects. The main analgesic agent - morphine is unfortunately a therapy associated with gastrointestinal side effects. It appears that the combination of oxycodone and naloxone available as Targin(®) (Mundipharma) is an alternative. The paper presents a case of a 45-year-old patient who was treated effectively with oxycodone/naloxone prolonged-release tablets. This treatment has proven to be effective in providing pain and constipation control.

The place of oxycodone/naloxone in chronic pain management.

Opioid analgesics are usually effective in the management of severe chronic pain. However, symptoms of opioid-induced bowel dysfunction (OIBD) are common during opioid therapy. Opioid-induced bowel dysfunction is often unsuccessfully managed due to limited effectiveness and numerous adverse effects of traditional laxatives. Newer treatment possibilities directed at the pathomechanism of OIBD comprise combined prolonged-release oxycodone with prolonged-release naloxone (oxycodone/naloxone) tablets. Oxycodone/naloxone provides effective analgesia with limited impact on bowel function as oxycodone displays high oral bioavailability and naloxone act as local antagonist on opioid receptors in the gastrointestinal tract due to nearly complete inactivation in the liver. Oxycodone/naloxone is administered to opioid-naive patients with severe pain and those unsuccessfully treated with weak opioids. Oxycodone/naloxone may be also administered to patients treated with strong opioids who experience intense symptoms of OIBD. Studies conducted to date indicate that oxycodone/naloxone is an important drug in chronic pain management, prevention and treatment of OIBD.

Oxycodone-Naloxone Combination Hinders Opioid Consumption in Osteoarthritic Chronic Low Back Pain: A Retrospective Study with Two Years of Follow-Up.

Chronic low back pain (CLBP) due to osteoarthritis represents a therapeutic challenge worldwide. Opioids are extensively used to treat such pain, but the development of tolerance, i.e., less susceptibility to the effects of the opioid, which can result in a need for higher doses to achieve the same analgesic effect, may limit their use. Animal models suggest that ultra-low doses of opioid antagonists combined with opioid agonists can decrease or block the development of opioid tolerance. In this retrospective study, we tested this hypothesis in humans. In 2019, 53 patients suffering from CLBP were treated with either Oxycodone and Naloxone Prolonged Release (27 patients, OXN patients) or Oxycodone Controlled Release (26 patients, OXY patients). The follow-up period lasted 2 years, during which 10 patients discontinued the treatment, 5 out of each group. The remaining 43 patients reached and maintained the targeted pain relief, but at 18 and 24 months, the OXY patients showed a significantly higher oxycodone consumption than OXN patients to reach the same level of pain relief. No cases of respiratory depression or opioid abuse were reported. There were no significant differences in the incidence of adverse effects between the two treatments, except for constipation, more common in OXY patients. From our results, we can affirm that a long-term opioid treatment with oxycodone-naloxone combination, when compared with oxycodone only, may significantly hinder the development of opioid tolerance. We were also able to confirm, in our cohort, the well known positive effect of naloxone in terms of opioid-induced bowel dysfunction incidence reduction.

Pharmaceutical opioid poisonings in Victoria, Australia: Rates and characteristics of a decade of emergency department presentations among nine pharmaceutical opioids.

BACKGROUND AND AIMS: Pharmaceutical opioids are a significant contributor to the global 'opioid crisis', yet few studies have comprehensively distinguished between opioid types. We measured whether a range of common pharmaceutical opioids varied in their contribution to the rates and characteristics of harm in a population-wide indicator of non-fatal overdose. DESIGN: Retrospective observational study of emergency department (ED) patient care records in the Victorian Emergency Minimum Data set (VEMD), July 2009 to June 2019. SETTING: Victoria, Australia. CASES: ED presentations for non-fatal overdose related to pharmaceutical opioid use (n = 5403), where the specific pharmaceutical opioid was documented. MEASUREMENTS: We compared harms across the nine individual pharmaceutical opioids most commonly sold, and considered where multiple opioids contributed to the overdose. We calculated supply-adjusted rates of ED presentations using Poisson regression and used multinomial logistic regression to compare demographic and clinical characteristics of presentations among nine distinct pharmaceutical opioids and a 10th category where multiple opioids were documented for the presentation. FINDINGS: There were wide differences, up to 27-fold, between supply-adjusted rates of overdose. When considering presentations with sole opioids, the highest supply-adjusted overdose rates [per 100 000 oral morphine equivalents (OME); 95% confidence interval (CI)] were for codeine (OME = 0.078, 95% CI = 0.073-0.08) and oxycodone (OME =0.029, 95% CI = 0.027-0.030) and the lowest were for tapentadol (OME = 0.004, 95% CI = 0.003-0.006) and fentanyl (OME = 0.003, 95% CI = 0.002-0.004). These rates appeared related to availability rather than opioid potency. Most (62%) poisonings involved females. Codeine, oxycodone and tramadol were associated with younger presentations (respectively, 59.5%, 41.7% and 49.8% of presentations were 12-34 years old), and intentional self-harm (respectively 65.2%, 50.6%, and 52.8% of presentations). Relative to morphine, fentanyl [ 0.32 relative risk ratio (RRR)] and methadone ( 0.58 RRR) presentations were less likely to be coded as self-harm. Relative to morphine-buprenorphine, codeine, oxycodone and tramadol presentations were significantly more likely to be associated with the less urgent triage categories (respectively 2.18, 1.80, 1.52, 1.65 RRR). CONCLUSIONS: In Victoria, Australia, rates and characteristics of emergency department presentations for pharmaceutical opioids show distinct variations by opioid type.

Oxycodone/naloxone prolonged-release tablets in patients with moderate-to-severe, chronic cancer pain: Challenges in the context of hepatic impairment.

Opioids such as oxycodone are recommended in the management of moderate-to-severe, chronic cancer pain. All opioids can potentially cause constipation, which may be a significant barrier to their use. Multiple randomised clinical trials have shown that the use of naloxone as a peripherally acting mu-opioid receptor antagonist, in combination with oxycodone can prevent or reduce opioid-induced constipation while having equivalent analgesic efficacy to oxycodone alone. However, clinical experience has shown that unexpected events may occur in some patients when unrecognized liver impairment is present. We describe the underlying biological reasons and propose simple, but effective steps to avoid this unusual but potentially serious occurrence. In healthy individuals, naloxone undergoes extensive hepatic first pass metabolism resulting in low systemic bioavailability. However, in patients with hepatic impairment, porto-systemic shunting can increase systemic bioavailability of naloxone, potentially compromising the analgesic efficacy of oral naloxone-oxycodone combinations. This reduced first pass effect can occur in a range of settings that may not always be apparent to the treating clinician, including silent cirrhosis, non-cirrhotic portal hypertension and disruption of liver internal vasculature by metastases. Hepatic function test results correlate poorly with presence and extent of liver disease, and are not indicative of porto-systemic shunting. Presence of hepatic impairment should thus be considered when medication-related outcomes with oxycodone-naloxone combination are not as expected, even if liver function test results are normal.

ENhANCE trial protocol: A multi-centre, randomised, phase IV trial comparing the efficacy of oxycodone/naloxone prolonged release (OXN PR) versus oxycodone prolonged release (Oxy PR) tablets in patients with advanced cancer.

Background: Oxycodone is a frequently used opioid in cancer. Opioid-induced constipation (OIC) is common. Oxycodone/Naloxone Prolonged Release (OXN PR) contains naloxone, which mitigates OIC. Trials have either focused on non-cancer pain, or conducted before significant experience of using OXN PR. This trial aims to: demonstrate (1) analgesic equivalence between OXN PR and Oxycodone Prolonged Release (Oxy PR), and (2) superiority of constipation outcomes in OXN PR compared to Oxy PR in cancer pain. Unlike other trials, it will only include patients with at least moderate pain scores (≥4/10), allow usual laxatives, and exclude potential liver dysfunction. Methods: This is a multi-centre, open-label, randomised, phase IV study of OXN PR vs Oxy PR in patients with cancer-related pain. The primary outcome is pain difference on Brief Pain Inventory-Short Form (BPI-SF) at 5 weeks. Secondary outcomes are comparison of other pain outcomes (BPI-SF) and neuropathic pain measures (Leeds Assessment of Neuropathic Symptoms & Signs (S-LANNS)), constipation (Bowel Function Index (BFI)), quality of life (EORTC-QLQ-C30), rescue analgesia use, total opioid dose, and total laxative dose over 5 weeks. Conclusion: The comparison of analgesic efficacy between both arms, and superiority of constipation in the OXN PR arm will add new knowledge on the comparisons of both agents, and oxycodone independently. This trial will extend knowledge of the effectiveness, safety, and adverse effect profiles of both drugs in terms of pain, constipation, quality of life outcomes for patients with cancer pain, and provide clinicians with high quality data to guide decision making. Trial registration: Name of the registry: ANZCTR. Trial registration number: ACTRN12619001282178. Date of registration: 17/09/2019. URL of trial registry record: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377673&isReview=trueProtocol version 2.1_28 August 2020.

Tapentadol and Oxycodone/Naloxone Prescribing Patterns in Primary Health Care in Catalonia, Spain: A Cross-Sectional Study.

OBJECTIVE: To characterize the use of tapentadol and the combination oxycodone/naloxone in primary health care. Data on their use and possible misuse will allow the identification of risk factors and to design protocols to reduce and prevent avoidable harm to patients being treated for pain. DESIGN: A descriptive, cross-sectional and multicenter study was performed. SETTING: Fifty-three primary health care teams, which provides healthcare for 1,300,000 inhabitants. PATIENTS: A total of 1840 patients had active prescriptions of tapentadol and 985 of oxycodone/naloxone. METHODS: Demographic (age, sex) and clinical (glomerular filtration rate; active liver disease; dosing and duration of treatment), prescribed daily dose (according to age, sex, length of treatment), concomitant analgesic treatment and diagnosis. Patient information was obtained from medical records. RESULTS: Most of the patients were women (>74.0% in both cases), and the average age was 69.3 years (women: 70.1±13.2; men: 66.7±13.9 years) in the case of tapentadol and 70.6 years (women: 64.0±13.6; men: 72.6±14.3 years) in the case of oxycodone/naloxone. Only 12.2% of patients taking tapentadol and 12.1% taking oxycodone/naloxone had a normal renal function. In both cases, 4.1% of patients had active liver disease. The average length of treatment was 246.4 days in oxycodone/naloxone and 199.0 days in tapentadol. It was recorded that 85.1% of patients in the case of tapentadol and 89.0% in the oxycodone/naloxone had at least another drug prescribed for pain. About 42.2% of patients treated with tapentadol and 34.4% of patients treated with oxycodone/naloxone had associated neuralgia as a diagnosis. CONCLUSION: The pattern of use and profile of patients with tapentadol and oxycodone/naloxone had more similarities than differences, and suggested that prescribing practice, and monitoring should be assessed regularly to ensure patient safety and effective management of pain.

Prolonged-Release (PR) Oxycodone/Naloxone Improves Bowel Function Compared with Oxycodone PR and Provides Effective Analgesia in Chinese Patients with Non-malignant Pain: A Randomized, Double-Blind Trial.

INTRODUCTION: Prolonged-release oxycodone/naloxone (OXN PR), combining an opioid analgesic with selective blockade of enteric µ-opioid receptors, provided effective analgesia and improved bowel function in patients with moderate-to-severe pain and opioid-induced constipation in clinical trials predominantly conducted in Western countries. This double-blind randomized controlled trial investigated OXN PR (N = 116) versus prolonged-release oxycodone (OXY PR, N = 115) for 8 weeks at doses up to 50 mg/day in patients with moderate-to-severe, chronic, non-malignant musculoskeletal pain and opioid-induced constipation recruited in China. METHODS: A total of 234 patients at least 18 years of age with non-malignant musculoskeletal pain for more than 4 weeks that was moderate-to-severe in intensity and required round-the-clock opioid therapy were randomized (1:1) to OXN PR or OXY PR. The primary endpoint was bowel function using the Bowel Function Index (BFI). Secondary endpoints included safety, Brief Pain Inventory-Short Form (BPI-SF), use of analgesic and laxative rescue medication, and health-related quality of life (EQ-5D). RESULTS: While BFI scores were comparable at baseline, at week 8 improvements were greater with OXN PR vs OXY PR (least squares mean [LSM] difference (95% CI) - 9.1 (- 14.0, - 4.2); P < 0.001. From weeks 2 to 8, mean BFI scores were in the range of normal bowel function (≤ 28.8) with OXN PR but were in the range of constipation (> 28.8) at all timepoints with OXY PR. Analgesia with OXN PR was similar and non-inferior to OXY PR on the basis of modified BPI-SF average 24-h pain scores at week 8: LSM difference (95% CI) - 0.3 (- 0.5, - 0.1); P < 0.001. The most frequent treatment-related AEs were nausea (OXN PR 5% vs OXY PR 6%) and dizziness (4% vs 4%). CONCLUSION: OXN PR provided clinically meaningful improvements in bowel function and effective analgesia in Chinese patients with moderate-to-severe musculoskeletal pain and pre-existing opioid-induced constipation. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01918098.

Advancing synthetic therapies for the treatment of restless legs syndrome.

Introduction: Restless Legs Syndrome/Willis-Ekbom disease (RLS/WED) is a common sensory-motor neurological disorder that impairs nocturnal rest causing decreased alertness, depressed mood, reduced job performance and poor quality of life. In patients affected by moderate to severe RLS/WED, a pharmacological treatment is mandatory. Areas covered: The present review is based on an extensive Internet and PubMed search from 1996 to 2019. It is focused on drugs currently used and under development (phase III and beyond) for the treatment of RLS/WED. Expert opinion: The drugs currently available for the treatment of the disease do not always allow for obtaining the optimal control of symptoms, in particular in the long-term treatment. Although initially effective, long-term dopaminergic treatment tends to wane over time and augmentation can occur. Updated international guidelines now recommend α2δ calcium channel ligand medications as the initial drug of choice. Oxycodone-naloxone demonstrated a significant and sustained treatment effect for patients with severe RLS/WED insufficiently controlled with previous treatments. Head-to-head trials of different drugs, as well as more studies on nondopaminergic agents and combination therapy, are greatly needed. Monoamine oxidase B inhibitors could be good candidates for the initial treatment of RLS/WED, sparing stronger dopaminergic agents for later stages of the disease.

The role of oxycodone/naloxone in the management of patients with pain and opioid-induced constipation.

INTRODUCTION: Common opioid adverse effects (AE) of the gastrointestinal tract include opioid-induced constipation (OIC) and opioid-induced bowel dysfunction (OIBD) with traditional laxatives being of limited efficacy, having AEs and not addressing the pathophysiology of OIC or OIBD. Targeted treatment comprises of PAMORA (peripherally acting mu-opioid receptor antagonists) and a combination of an opioid receptor agonist with its antagonist, namely prolonged-release oxycodone with prolonged-release naloxone (OXN) tablets at a fixed ratio of 2:1. Oxycodone provides analgesia, whereas naloxone prevents binding or displaces it from opioid receptors located in the gut wall. Areas covered: The authors review the role of OXN in the management of patients with pain and OIC. A literature search was performed using the search terms 'oxycodone/naloxone' and 'opioid-induced constipation' using the PubMed database up to October 2018. Expert opinion: OXN delivers analgesia comparable (or superior versus placebo and in observational studies) to oxycodone alone and other opioids with a limited or decreased disturbing effect on bowel function. OXN in daily doses of up to 160 mg/80 mg provides effective analgesia with little negative impact on bowel function. OXN may be successfully used in patients with chronic pain, to prevent or treat symptoms of OIC and OIBD.

Spontaneously reported adverse drug events related to tapentadol and oxycodone/naloxone in Australia.

BACKGROUND: The rapid increase in prescribing and use of opioids for noncancer pain has coincided with an increase in opioid-related adverse drug events (ADEs). The objective of our study was to describe ADEs related to tapentadol and oxycodone/naloxone spontaneously reported to the Australian Therapeutic Goods Administration (TGA). METHODS: Public case detail reports for tapentadol (September 2013-March 2017) and oxycodone/naloxone (April 2011-March 2017) were sourced from the TGA. The total number of public case detail reports for tapentadol were 104 and 249 for oxycodone/naloxone. Demographic characteristics of patients, concomitant medications, causality assessment and outcome were described for each opioid according to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class. RESULTS: The most prevalent ADEs for tapentadol were nervous system disorders (n = 52, 50%), psychiatric (n = 34, 32.7%), gastrointestinal (n = 18, 17.3%), and general disorders and administration site conditions (n = 21, 20.2%). Sixteen (23.2%) of 69 nervous system disorders reaction terms were consistent with serotonin syndrome of which 14 (87.5%) involved documented coadministration with another serotonergic medication. The most prevalent ADEs for oxycodone/naloxone were psychiatric disorders (n = 78, 31.3%), gastrointestinal (n = 73, 29.3%), general disorders and administration site conditions (n = 87, 35%), and nervous system disorders (n = 62, 24.9%). There were 40 (16%) public case detail reports for oxycodone/naloxone with the MedDRA reaction terms 'drug withdrawal syndrome' and 'withdrawal syndrome'. CONCLUSION: The profiles of spontaneous ADE reports for tapentadol and oxycodone/naloxone are largely consistent with their premarketing randomized controlled studies and profiles of opioids in general. Further research into the risk of serotonin syndrome with tapentadol use is warranted. The ADEs suggest clinicians should be cautious when switching patients to oxycodone/naloxone from other opioids.

Analgesic Efficacy and Safety of Prolonged-Release Oxycodone/Naloxone in Korean Patients with Chronic Pain from Spinal Disorders.

BACKGROUND: A prolonged-release formulation of oxycodone/naloxone has been shown to be effective in European populations for the management of chronic moderate to severe pain. However, no clinical data exist for its use in Korean patients. The objective of this study was to assess efficacy and safety of prolonged-release oxycodone/naloxone in Korean patients for management of chronic moderate-to-severe pain. METHODS: In this multicenter, single-arm, open-label, phase IV study, Korean adults with moderate-to-severe spinal disorder-related pain that was not satisfactorily controlled with weak opioids and nonsteroidal anti-inflammatory drugs received prolonged-release oral oxycodone/naloxone at a starting dose of 10/5 mg/day (maximum 80/40 mg/day) for 8 weeks. Changes in pain intensity and quality of life (QoL) were measured using a numeric rating scale (NRS, 0-10) and the Korean-language EuroQol-five dimensions questionnaire, respectively. RESULTS: Among 209 patients assessed for efficacy, the mean NRS pain score was reduced by 25.9% between baseline and week 8 of treatment (p < 0.0001). There was also a significant improvement in QoL from baseline to week 8 (p < 0.0001). The incidence of adverse drug reactions was 27.7%, the most common being nausea, constipation, and dizziness; 77.9% of these adverse drug reactions had resolved or were resolving at the end of the study. CONCLUSIONS: Prolonged-release oxycodone/naloxone provided significant and clinically relevant reductions in pain intensity and improved QoL in Korean patients with chronic spinal disorders. (ClinicalTrials.gov identifier: NCT01811238).

Prolonged-release oxycodone/naloxone reduces opioid-induced constipation and improves quality of life in laxative-refractory patients: results of an observational study.

BACKGROUND: Opioids are an effective treatment for moderate-to-severe pain. However, they are associated with a number of gastrointestinal side effects, most commonly constipation. Laxatives do not target the underlying mechanism of opioid-induced constipation (OIC), so many patients do not have their symptoms resolved. Fixed-dose prolonged-release (PR) oxycodone/naloxone (OXN) tablets contain the opioid agonist oxycodone and the opioid antagonist naloxone. Nal-oxone blocks the action of oxycodone in the gut without compromising its analgesic effects. AIM: To evaluate the effectiveness of PR OXN in patients with severe pain who had laxative-refractory OIC with their previous opioid. METHODS: The study was carried out in 13 centers across the UK and Ireland, using a bespoke online tool to capture patients' data. Patients were reviewed according to normal clinical practice of each center and rated any changes in their constipation and quality of life (QoL) since starting PR OXN. Any change in patients' laxative use was also recorded. RESULTS: One hundred and seven patients were entered into the database, and 81 went on to attend at least one review. Of these, 54 (66.7%) reported an improvement in constipation and 50 (61.7%) reported an improvement in QoL since starting PR OXN. Fifty-seven patients (70.4%) said they had reduced laxative intake; 48 (59.3%) only needed laxatives as required. CONCLUSION: PR OXN reduced symptoms of constipation, improved QoL and reduced laxative intake in patients with OIC. It has a potential place early in any treatment strategy for severe pain in patients using opioids, particularly in patients who may be predisposed to constipation.

Opioid-Induced Bowel Dysfunction in Patients Undergoing Spine Surgery: Comparison of Oxycodone and Oxycodone-Naloxone Treatment.

INTRODUCTION: Opioids are needed for postoperative pain in spine surgery patients, but opioid-induced constipation is a harmful adverse event. The aim of this clinical trial was to compare the use of a controlled-release oxycodone-naloxone combination product with oxycodone controlled-release tablets in these patients. The main outcome measure was the prevalence of constipation at 7 days postoperatively assessed with a Bowel Function Index questionnaire. A follow-up assessment at 21 days after surgery was also included. METHODS: A total of 180 patients undergoing spine surgery, 91 having preoperative opioids in use and 89 opioid-naïve, were randomized to receive twice-daily oxycodone 10 mg or oxycodone-naloxone 10/5 mg controlled-release tablets for the first 7 postoperative days. Patients were followed-up for 21 days after surgery. RESULTS: At baseline, prevalence of constipation was common both in the opioid-naïve-25/87 (29%) and on-opioid groups 43/90 (48%) (P = 0.009). This increased at 7 days postoperatively with no difference between the groups, 54/89 with oxycodone and 54/88 with oxycodone-naloxone had constipation. At 21 days, constipation was less than in the baseline in both groups, in the opioid-naïve group the prevalence of constipation was 3/43 (7%) in patients with oxycodone-naloxone compared to 9/44 (21%) with oxycodone (effect size 0.68; P = 0.068). Both study compounds provided similar pain relief and were well tolerated. CONCLUSION: In patients presented for back surgery, the prevalence of constipation was significantly higher than that in the community. In opioid-naïve subjects, oxycodone-naloxone was beneficial concerning constipation; but this was not distinguishable in subjects with chronic opioid use. The analgesic efficacy of oxycodone and oxycodone-naloxone was similar. TRIAL REGISTRATION: European Clinical Trials Database (EudraCT no. 2012-001816-42) and ClinicalTrials.gov database (Identifier: NCT02573922).

A comparison between the administration of oral prolonged-release oxycodone-naloxone and transdermal fentanyl in patients with moderate-to-severe cancer pain: a propensity score analysis.

BACKGROUND: Opioids are the most important pharmacological treatment for moderate-to-severe cancer pain, but side effects limit their use. Transdermal fentanyl (TDF) and oral prolonged-release oxycodone-naloxone (OXN-PR) are effective in controlling chronic pain, with less constipation compared to other opioids. However, TDF and OXN-PR have never been directly compared. PATIENTS AND METHODS: Cancer patients with moderate-to-severe chronic pain were consecutively enrolled in two prospective 28-day trials, received either TDF or OXN-PR, and were assessed at baseline and after 7, 14, 21, and 28 days. The primary endpoint was 28-day analgesic response rate (average pain intensity decrease ≥30% from baseline). Other outcome measures included opioid daily dose changes over time; need for adjuvant analgesics; number of switches; premature discontinuation; presence and severity of constipation; and other adverse drug reactions. To compare the efficacy and the safety of TDF and OXN-PR, we used the propensity score analysis to adjust for heterogeneity between the two patient groups. RESULTS: Three hundred ten out of 336 patients originally treated (119 TDF and 191 OXN-PR) were included in the comparative analysis. The amount of responders was comparable after TDF (75.3%) and OXN-PR administration (82.9%, not significant [NS]). The final opioid daily dose expressed as morphine equivalent was 113.6 mg for TDF and 44.5 mg for OXN-PR (p<0.0001). A daily opioid dose escalation >5% was less common after OXN-PR (19.3%) than after TDS administration (37.9%, p<0.0001). Opioid switches and discontinuation were similar in both groups. Severe constipation in the two groups was comparable (32.6% after TDF vs 24.7% after OXN-PR, NS). Nausea, vomiting, and dry mouth were significantly less frequent in the OXN-PR group than in the TDF group. CONCLUSION: Despite a similar analgesic activity in moderate-to-severe cancer pain, OXN-PR is characterized by lower daily dosages, less need for drug escalation, and fewer side effects compared to TDF.

Prolonged release oxycodone and naloxone treatment counteracts opioid-induced constipation in patients with severe pain compared to previous analgesic treatment.

OBJECTIVE: Treatment with prolonged-release oxycodone/naloxone (PR OXN) has been shown to improve opioid induced constipation (OIC) in constipated patients. This publication reports on a real-life observational study investigating the efficacy of PR OXN with regard to bowel function in patients switching to PR OXN from WHO step 1, step 2 and step 3 opioids. METHODS: Patients with chronic pain experiencing insufficient pain relief and/or unacceptable side effects were switched to PR OXN and monitored in this observational study with respect to efficacy regarding bowel function and efficacy regarding pain relief in comparison with previous analgesic therapy. A patient was considered a responder with respect to efficacy if this assessment was "slightly better", "better" or "much better" compared with previous therapy. Bowel function index, pain intensity, quality of life, laxative medication use, and safety analgesic were also evaluated. RESULTS: A total of 1338 patients (mean [SD] age 64.3 [14.9], 63% female) were observed for 43 [3-166] days (median [range]) during treatment with PR OXN. Overall response rate regarding bowel function efficacy was 82.5%. Patients with symptoms of constipation at study entry obtained a clinically relevant improvement of the bowel function index (BFI) within the first 2 weeks of PR OXN treatment. Non-constipated patients at study entry maintained normal bowel function despite switching to treatment with the opioid PR OXN. CONCLUSION: In conclusion, treatment with PR OXN results in a significant and clinically relevant improvement of bowel function. During the observation of the treatment with PR OXN patients reported an improvement of quality of life (QoL). More interestingly, non-constipated patients maintained a normal bowel function, showing prevention of constipation despite the use of an opioid.