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Ilona Steigerwald - One of the best experts on this subject based on the ideXlab platform.
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effectiveness of tapentadol prolonged release pr compared with Oxycodone naloxone pr for the management of severe chronic low back pain with a neuropathic component a randomized controlled open label phase 3b 4 study
Pain Practice, 2016Co-Authors: Ralf Baron, Dietmar Falke, E Martinmola, Matthias Muller, Rudolf Likar, Francisco J Blanco, Lieven Kennes, Ilona SteigerwaldAbstract:Objective To evaluate the effectiveness of tapentadol prolonged release (PR) vs. Oxycodone/naloxone PR in non–opioid-pretreated patients with severe chronic low back pain with a neuropathic pain component. Methods Eligible patients (average pain intensity [numerical rating scale-3 (NRS-3)] ≥6; painDETECT positive/unclear) were randomized to twice-daily tapentadol PR 50 mg or Oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or Oxycodone/naloxone PR 40 mg/20 mg plus Oxycodone PR 10 mg), target doses were continued for 9 weeks. The primary effectiveness endpoint was the change in NRS-3 from baseline to final evaluation; the exact repeated confidence interval (RCI) for tapentadol PR minus Oxycodone/naloxone PR was used to establish noninferiority (upper limit <1.3) and superiority (confirmatory analyses). Results For the primary effectiveness endpoint, tapentadol PR was noninferior to Oxycodone/naloxone PR (97.5% RCI: [−1.820, −0.184]; P < 0.001). This exact RCI also yielded evidence of superiority for tapentadol PR vs. Oxycodone/naloxone PR (significantly greater reduction in pain intensity; P = 0.003). Improvements (baseline to final evaluation) in painDETECT and Neuropathic Pain Symptom Inventory scores were significantly greater with tapentadol PR vs. Oxycodone/naloxone PR (all P ≤ 0.005). Conclusions The study was formally shown to be positive and demonstrated, in the primary effectiveness endpoint, the noninferiority for tapentadol PR vs. Oxycodone/naloxone PR. The effectiveness of tapentadol PR was superior to that of Oxycodone/naloxone PR by means of clinical relevance and statistical significance (confirmatory evidence of superiority). Tapentadol PR was associated with significantly greater improvements in neuropathic pain-related symptoms and global health status than Oxycodone/naloxone PR and with a significantly better gastrointestinal tolerability profile. Tapentadol PR may be considered a first-line option for managing severe chronic low back pain with a neuropathic pain component.
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tolerability safety and quality of life with tapentadol prolonged release pr compared with Oxycodone naloxone pr in patients with severe chronic low back pain with a neuropathic component a randomized controlled open label phase 3b 4 trial
Pain Practice, 2016Co-Authors: Ralf Baron, Dietmar Falke, Matthias Muller, Lieven Kennes, Janpeter Jansen, Andreas Binder, Manuel Pombosuarez, Ilona SteigerwaldAbstract:Objective To evaluate tolerability, safety, and quality-of-life outcomes in non-opioid-pretreated patients with severe chronic low back pain with a neuropathic component receiving tapentadol PR vs. Oxycodone/naloxone PR. Methods Eligible patients (average pain intensity [numerical rating scale] ≥ 6; painDETECT positive/unclear ratings) were randomized to twice-daily tapentadol PR 50 mg or Oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or Oxycodone/naloxone PR 40 mg/20 mg plus Oxycodone PR 10 mg), target doses were continued for 9 weeks. Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) total score from baseline to final evaluation was a primary endpoint. Results For the primary tolerability-related endpoint, the 97.5% exact repeated confidence interval for tapentadol PR minus Oxycodone/naloxone PR for the PAC-SYM total score was [−0.259, 0.121], showing noninferiority (upper limit < 0.7). Incidences of constipation and vomiting were significantly lower with tapentadol PR than Oxycodone/naloxone PR (P ≤ 0.045). Confirmatory superiority based on formal noninferiority was shown for the primary effectiveness endpoint (change from baseline to final evaluation in pain intensity) for tapentadol PR vs. Oxycodone/naloxone PR (presented separately). Improvements in the Short Form-12 physical component summary and EuroQol-5 Dimension health status index and health state assessment were significantly greater with tapentadol PR vs. Oxycodone/naloxone PR (P ≤ 0.024). Conclusions Tapentadol PR had a minimal impact on bowel function (noninferior to Oxycodone/naloxone PR) and, along with superior effectiveness (presented separately), was associated with significantly lower incidences of constipation and vomiting and significant improvements in quality-of-life measures vs. Oxycodone/naloxone PR.
Eija Kalso - One of the best experts on this subject based on the ideXlab platform.
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ketamine and norketamine attenuate Oxycodone tolerance markedly less than that of morphine from behaviour to drug availability
BJA: British Journal of Anaesthesia, 2017Co-Authors: Tuomas Lilius, E Kangas, Mikko Niemi, Pekka Rauhala, Eija KalsoAbstract:Abstract Background Ketamine attenuates morphine tolerance by antagonising N-methyl-d-aspartate receptors. However, a pharmacokinetic interaction between morphine and ketamine has also been suggested. The interaction between Oxycodone and ketamine is unclear. We studied the effects of ketamine and norketamine on the attenuation of morphine and Oxycodone tolerance focusing on both the pharmacodynamic and pharmacokinetic interactions. Methods Morphine 9.6 mg day−1 or Oxycodone 3.6 mg day−1 was delivered to Sprague–Dawley rats by subcutaneous pumps. Once tolerance had developed, the rats received subcutaneous injections of ketamine or norketamine. Tail-flick, hot-plate, and rotarod tests were performed. Drug concentrations were measured with high-performance liquid chromatography–tandem mass spectrometry. Results Anti-nociceptive tolerance to morphine and Oxycodone developed similarly by Day 6. Acute ketamine 10 mg kg−1 and norketamine 30 mg kg−1 attenuated morphine tolerance for 120 and 150 min, respectively, whereas in Oxycodone-tolerant rats the effect lasted only 60 min. Both ketamine and norketamine increased the brain and serum concentrations of morphine, and inhibited its metabolism to morphine-3-glucuronide, whereas Oxycodone concentrations were not changed. Morphine, but not Oxycodone, pretreatment increased the brain and serum concentrations of ketamine and norketamine. Ketamine, but not norketamine, significantly impaired the motor coordination. Conclusions Ketamine and norketamine attenuated morphine tolerance more effectively than Oxycodone tolerance. Ketamine and norketamine increased morphine, but not Oxycodone brain concentrations, which may partly explain this difference. Norketamine is effective in attenuating morphine tolerance with minor effects on motor coordination. These results warrant pharmacokinetic studies in patients who are co-treated with ketamine and opioids.
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does the pharmacology of Oxycodone justify its increasing use as an analgesic
Trends in Pharmacological Sciences, 2013Co-Authors: Klaus T Olkkola, Vesa K Kontinen, Teijo I Saari, Eija KalsoAbstract:Oxycodone is a semisynthetic opioid analgesic that is increasingly used for the treatment of acute, cancer, and chronic non-malignant pain. Oxycodone was synthesized in 1917 but its pharmacological properties were not thoroughly studied until recently. Oxycodone is a fairly selective μ-opioid receptor agonist, but there is a striking discrepancy between the relatively low binding potential and G protein activation by Oxycodone and its analgesic efficacy. It has been claimed that this is because of active metabolites and enhanced passage to the central nervous system by active transport. We critically review studies on the basic pharmacology of Oxycodone and on its pharmacokinetics and pharmacodynamics in humans. In particular, the role of pharmacogenomics and population pharmacokinetics in understanding the properties of Oxycodone is discussed in detail. We compare Oxycodone with morphine, the standard opioid in clinical use.
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antinociception by spinal and systemic Oxycodone why does the route make a difference in vitro and in vivo studies in rats
Anesthesiology, 2006Co-Authors: Kim Lemberg, Vesa K Kontinen, Antti Siiskonen, Kaarin Viljakka, Jari Ylikauhaluoma, Esa R Korpi, Eija KalsoAbstract:Background The pharmacology of Oxycodone is poorly understood despite its growing clinical use. The discrepancy between its good clinical effectiveness after systemic administration and the loss of potency after spinal administration led the authors to study the pharmacodynamic effects of Oxycodone and its metabolites using in vivo and in vitro models in rats. Methods Male Sprague-Dawley rats were used in hot-plate, tail-flick, and paw-pressure tests to study the antinociceptive properties of morphine, Oxycodone, and its metabolites oxymorphone and norOxycodone. Mu-opioid receptor agonist-stimulated GTPgamma[S] autoradiography was used to study G-protein activation induced by morphine, Oxycodone, and oxymorphone in the rat brain and spinal cord. Spontaneous locomotor activity was measured to assess possible sedation or motor dysfunction. Naloxone and the selective kappa-opioid receptor antagonist nor-binaltorphimine were used to study the opioid receptor selectivity of the drugs. Results Oxycodone showed lower efficacy and potency to stimulate GTPgamma[S] binding in the spinal cord and periaqueductal gray compared with morphine and oxymorphone. This could relate to the fact that Oxycodone produced only weak naloxone-reversible antinociception after intrathecal administration. It also suggests that the metabolites may have a role in Oxycodone-induced analgesia in rats. Intrathecal oxymorphone produced strong long-lasting antinociception, whereas norOxycodone produced antinociception with very high doses only. Subcutaneous administration of Oxycodone and oxymorphone produced thermal and mechanical antinociception that was reversed by naloxone but not by nor-binaltorphimine. Oxymorphone was more potent than Oxycodone, particularly in the hot-plate and paw-pressure tests. Conclusions The low intrathecal potency of Oxycodone in rats seems be related to its low efficacy and potency to stimulate mu-opioid receptor activation in the spinal cord.
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proceedings of the symposium updates of the clinical pharmacology of opioids with special attention to long acting drugs Oxycodone
Journal of Pain and Symptom Management, 2005Co-Authors: Eija KalsoAbstract:Oxycodone has been in clinical use since 1917. Parenteral Oxycodone was used mainly for the treatment of acute postoperative pain whereas combinations, for example, Oxycodone and acetaminophen, were used for moderate pain. Since the introduction of controlled- release Oxycodone, it has been used to manage cancer-related pain and chronic non-cancer- related pain problems. Controlled studies have been performed in postoperative pain, cancer pain, osteoarthritis-related pain, and neuropathic pain due to postherpetic neuralgia and diabetic neuropathy. The pharmacodynamic effects of Oxycodone are typical of a µ-opioid agonist. Oxycodone closely resembles morphine but it has some distinct differences, particularly in its pharmacokinetic profile. Being an old drug, the basic pharmacology of Oxycodone has been a neglected field of research. J Pain Symptom Manage 2005;29:S47-S56. 2005 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
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controlled release Oxycodone and morphine in cancer related pain
Pain, 1997Co-Authors: Tarja Heiskanen, Eija KalsoAbstract:Controlled-release (CR) formulations of Oxycodone and morphine were compared in 45 patients with chronic cancer pain. The study was started with an open-label, randomised titration phase to achieve stable pain control for at least 48 h, followed by a double-blind, randomised, crossover phase in two periods, 3-6 days each. To blind the study using available tablet strengths, the dose ratio of Oxycodone to morphine was set at 2:3. A daily telephone contact was maintained between the patient and the investigator. The patients were asked to assess pain intensity four times a day and acceptability of therapy twice daily, and to record possible adverse effects. Pharmacodynamic evaluations were performed at the end of each double-blind period. The patients were allowed to use escape analgesic (respective opioid as oral solution) as needed. Twenty-seven patients were evaluable for both safety and efficacy. Pain was well-controlled during both stable phases. When the period effect was taken into account the two opioids provided comparable analgesia. If the results of the two periods were combined, the patients consumed significantly more escape doses and the mean pain intensities were significantly greater with CR Oxycodone. The total opioid consumption ratio of Oxycodone to morphine was 2:3 when Oxycodone was administered first, and 3:4 when Oxycodone was administered after morphine. The total incidence of adverse experiences reported by the patients was similar, but significantly more vomiting occurred with morphine, whereas constipation was more common with Oxycodone.
Ralf Baron - One of the best experts on this subject based on the ideXlab platform.
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effectiveness of tapentadol prolonged release pr compared with Oxycodone naloxone pr for the management of severe chronic low back pain with a neuropathic component a randomized controlled open label phase 3b 4 study
Pain Practice, 2016Co-Authors: Ralf Baron, Dietmar Falke, E Martinmola, Matthias Muller, Rudolf Likar, Francisco J Blanco, Lieven Kennes, Ilona SteigerwaldAbstract:Objective To evaluate the effectiveness of tapentadol prolonged release (PR) vs. Oxycodone/naloxone PR in non–opioid-pretreated patients with severe chronic low back pain with a neuropathic pain component. Methods Eligible patients (average pain intensity [numerical rating scale-3 (NRS-3)] ≥6; painDETECT positive/unclear) were randomized to twice-daily tapentadol PR 50 mg or Oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or Oxycodone/naloxone PR 40 mg/20 mg plus Oxycodone PR 10 mg), target doses were continued for 9 weeks. The primary effectiveness endpoint was the change in NRS-3 from baseline to final evaluation; the exact repeated confidence interval (RCI) for tapentadol PR minus Oxycodone/naloxone PR was used to establish noninferiority (upper limit <1.3) and superiority (confirmatory analyses). Results For the primary effectiveness endpoint, tapentadol PR was noninferior to Oxycodone/naloxone PR (97.5% RCI: [−1.820, −0.184]; P < 0.001). This exact RCI also yielded evidence of superiority for tapentadol PR vs. Oxycodone/naloxone PR (significantly greater reduction in pain intensity; P = 0.003). Improvements (baseline to final evaluation) in painDETECT and Neuropathic Pain Symptom Inventory scores were significantly greater with tapentadol PR vs. Oxycodone/naloxone PR (all P ≤ 0.005). Conclusions The study was formally shown to be positive and demonstrated, in the primary effectiveness endpoint, the noninferiority for tapentadol PR vs. Oxycodone/naloxone PR. The effectiveness of tapentadol PR was superior to that of Oxycodone/naloxone PR by means of clinical relevance and statistical significance (confirmatory evidence of superiority). Tapentadol PR was associated with significantly greater improvements in neuropathic pain-related symptoms and global health status than Oxycodone/naloxone PR and with a significantly better gastrointestinal tolerability profile. Tapentadol PR may be considered a first-line option for managing severe chronic low back pain with a neuropathic pain component.
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tolerability safety and quality of life with tapentadol prolonged release pr compared with Oxycodone naloxone pr in patients with severe chronic low back pain with a neuropathic component a randomized controlled open label phase 3b 4 trial
Pain Practice, 2016Co-Authors: Ralf Baron, Dietmar Falke, Matthias Muller, Lieven Kennes, Janpeter Jansen, Andreas Binder, Manuel Pombosuarez, Ilona SteigerwaldAbstract:Objective To evaluate tolerability, safety, and quality-of-life outcomes in non-opioid-pretreated patients with severe chronic low back pain with a neuropathic component receiving tapentadol PR vs. Oxycodone/naloxone PR. Methods Eligible patients (average pain intensity [numerical rating scale] ≥ 6; painDETECT positive/unclear ratings) were randomized to twice-daily tapentadol PR 50 mg or Oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or Oxycodone/naloxone PR 40 mg/20 mg plus Oxycodone PR 10 mg), target doses were continued for 9 weeks. Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) total score from baseline to final evaluation was a primary endpoint. Results For the primary tolerability-related endpoint, the 97.5% exact repeated confidence interval for tapentadol PR minus Oxycodone/naloxone PR for the PAC-SYM total score was [−0.259, 0.121], showing noninferiority (upper limit < 0.7). Incidences of constipation and vomiting were significantly lower with tapentadol PR than Oxycodone/naloxone PR (P ≤ 0.045). Confirmatory superiority based on formal noninferiority was shown for the primary effectiveness endpoint (change from baseline to final evaluation in pain intensity) for tapentadol PR vs. Oxycodone/naloxone PR (presented separately). Improvements in the Short Form-12 physical component summary and EuroQol-5 Dimension health status index and health state assessment were significantly greater with tapentadol PR vs. Oxycodone/naloxone PR (P ≤ 0.024). Conclusions Tapentadol PR had a minimal impact on bowel function (noninferior to Oxycodone/naloxone PR) and, along with superior effectiveness (presented separately), was associated with significantly lower incidences of constipation and vomiting and significant improvements in quality-of-life measures vs. Oxycodone/naloxone PR.
Michael Hopp - One of the best experts on this subject based on the ideXlab platform.
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naloxone as part of a prolonged release Oxycodone naloxone combination reduces Oxycodone induced slowing of gastrointestinal transit in healthy volunteers
Expert Opinion on Investigational Drugs, 2011Co-Authors: Kevin Smith, Michael Hopp, Gill Mundin, Simon Bond, Paul Bailey, Jo Woodward, Karuppan Palaniappan, Ann Church, Marie C Limb, Alyson ConnorAbstract:Objectives: This exploratory study in healthy volunteers investigated the effect of single doses of Oxycodone on gastrointestinal (GI) transit time and the degree to which a single dose of naloxone reverses the Oxycodone-induced effect. Methods: Fifteen healthy male volunteers received: Oxycodone 10 and 20 mg, Oxycodone/naloxone 10/5 and 20/10 mg (all as prolonged release tablets) and placebo. Each dose was radiolabelled and administered with a capsule containing radiolabelled resin (surrogate for GI contents). Results: Scintigraphic analysis showed that 20 mg Oxycodone significantly increased colon arrival time (mean 7.19 vs 5.15 h for placebo, p = 0.0159). Mean colon arrival time for Oxycodone/naloxone 20/10 mg (5.16 h) was similar to placebo, although the difference between Oxycodone/naloxone 20/10 mg versus Oxycodone 20 mg was not significant (p = 0.0653). Colonic geometric centre analysis showed a significant increase in mean time for the resin to reach the colon following Oxycodone 10 and 20 mg comp...
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a randomised controlled trial with prolonged release oral Oxycodone and naloxone to prevent and reverse opioid induced constipation
European Journal of Pain, 2009Co-Authors: Winfried Meissner, Michael Hopp, Petra Leyendecker, Christian Ruckes, Wolfgang Fleischer, Stefan Muellerlissner, J Nadstawek, Stefan Wirz, Karen ReimerAbstract: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 80 mg/day) were randomised to receive 10, 20, 40 mg/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, 10 mg, 20 mg and 40 mg naloxone dose, and remained unchanged during treatment. Bowel function improved with increasing naloxone dose. Naloxone 20 mg and 40 mg 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.
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analgesic efficacy and safety of Oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain
The Journal of Pain, 2008Co-Authors: Dana Vondrackova, Michael Hopp, Petra Leyendecker, Winfried Meissner, Istvan Szombati, Kai Hermanns, Christian Ruckes, Susanne Weber, Birgit Grothe, Wolfgang FleischerAbstract:Abstract This randomized, double-blind, placebo- and active-controlled, parallel-group study was designed to demonstrate the superiority of Oxycodone in combination with naloxone in a prolonged release (PR) formulation over placebo with respect to analgesic efficacy. The active control group was included for sensitivity and safety analyses, and furthermore to compare the analgesic efficacy and bowel function of Oxycodone PR/naloxone PR with Oxycodone PR alone. The analgesic efficacy was measured as the time from the initial dose of study medication to multiple pain events (ie, inadequate analgesia) in patients with moderate to severe chronic low back pain. The full analysis population consisted of 463 patients. The times to recurrent pain events were significantly longer in the Oxycodone PR/naloxone PR group compared with placebo ( P P Perspective This study evaluated the analgesic efficacy and safety of the combination of Oxycodone PR/naloxone PR in chronic nonmalignant pain. Opioids are often reduced in dosage or even discontinued as a result of impaired bowel function, leading to insufficient pain treatment. Not only does Oxycodone PR/naloxone PR demonstrate analgesic efficacy comparable with Oxycodone PR, but it also improves opioid-induced bowel dysfunction, and may therefore improve the acceptability of long-term opioid treatment for chronic pain.
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fixed ratio combination Oxycodone naloxone compared with Oxycodone alone for the relief of opioid induced constipation in moderate to severe noncancer pain
Current Medical Research and Opinion, 2008Co-Authors: Karen H Simpson, Michael Hopp, Petra Leyendecker, S Mullerlissner, O Lowenstein, J De Andres, Troy J Ferrarons, B Bosse, B Krain, T NicholsAbstract:ABSTRACTObjective: Opioid therapy is frequently associated with treatment-limiting constipation. Naloxone is an opioid antagonist with low oral systemic bioavailability. This Phase III clinical trial assessed the safety and efficacy of an oral fixed-ratio combination of Oxycodone prolonged-release (PR) and naloxone PR compared with Oxycodone PR in relieving opioid-induced constipation.Study design: This double-blind, multicenter trial was conducted in specialist and primary care centers in four European countries in an out-patients setting. The study included 322 adult patients with moderate-to-severe, noncancer pain requiring opioid therapy in a range of ≥20 mg/day and ≤50 mg/day Oxycodone. Following a run-in phase patients were randomized to receive Oxycodone PR/naloxone PR or Oxycodone PR for 12 weeks. The primary outcome was improvement in constipation as measured using the Bowel Function Index (BFI). Secondary/exploratory assessments focused on pain intensity and additional bowel parameters.Trial reg...
Wolfgang Fleischer - One of the best experts on this subject based on the ideXlab platform.
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a randomised controlled trial with prolonged release oral Oxycodone and naloxone to prevent and reverse opioid induced constipation
European Journal of Pain, 2009Co-Authors: Winfried Meissner, Michael Hopp, Petra Leyendecker, Christian Ruckes, Wolfgang Fleischer, Stefan Muellerlissner, J Nadstawek, Stefan Wirz, Karen ReimerAbstract: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 80 mg/day) were randomised to receive 10, 20, 40 mg/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, 10 mg, 20 mg and 40 mg naloxone dose, and remained unchanged during treatment. Bowel function improved with increasing naloxone dose. Naloxone 20 mg and 40 mg 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.
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analgesic efficacy and safety of Oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain
The Journal of Pain, 2008Co-Authors: Dana Vondrackova, Michael Hopp, Petra Leyendecker, Winfried Meissner, Istvan Szombati, Kai Hermanns, Christian Ruckes, Susanne Weber, Birgit Grothe, Wolfgang FleischerAbstract:Abstract This randomized, double-blind, placebo- and active-controlled, parallel-group study was designed to demonstrate the superiority of Oxycodone in combination with naloxone in a prolonged release (PR) formulation over placebo with respect to analgesic efficacy. The active control group was included for sensitivity and safety analyses, and furthermore to compare the analgesic efficacy and bowel function of Oxycodone PR/naloxone PR with Oxycodone PR alone. The analgesic efficacy was measured as the time from the initial dose of study medication to multiple pain events (ie, inadequate analgesia) in patients with moderate to severe chronic low back pain. The full analysis population consisted of 463 patients. The times to recurrent pain events were significantly longer in the Oxycodone PR/naloxone PR group compared with placebo ( P P Perspective This study evaluated the analgesic efficacy and safety of the combination of Oxycodone PR/naloxone PR in chronic nonmalignant pain. Opioids are often reduced in dosage or even discontinued as a result of impaired bowel function, leading to insufficient pain treatment. Not only does Oxycodone PR/naloxone PR demonstrate analgesic efficacy comparable with Oxycodone PR, but it also improves opioid-induced bowel dysfunction, and may therefore improve the acceptability of long-term opioid treatment for chronic pain.