Controlled-release Oxycodone Research Articles

1793P - Painkiller-related dizziness in malignant tumors: A systematic review

Background: To our knowledge, there is no systematic review on painkiller-related dizziness, which often occurs. Methods: Papers from core clinical journals on PubMed-database resulted in 340 articles on dizziness in malignant tumors until 31st Dec 2017. Eight studies with level of evidence (LoE) 1 focused on dizziness as a side effect of painkillers. Results: In a meta-analysis on codeine, dizziness was reported in 18.06 % of patients (LoE 1a) [1]. In randomized controlled trials (LoE 1b), oxycodone-associated dizziness was only seen in controlled release (8.3 %) and not in immediate release oxycodone [2]. In a systematic review (LoE 1a) [3], controlled release oxycodone was associated with 11.9 % of dizziness reports. A meta-analysis on immediate release morphine and transmucosal fentanyl (7 % dizziness) favoured transmucosal fentanyl for breakthrough cancer pain, but did not differentiate between the painkillers for dizziness [4]. Effective analgesia with rare (1.8 to 7.5 %) events of dizziness was reported for intranasal fentanyl spray (LoE 1b) [5]. For long-acting analgesia, a systematic review favoured transdermal fentanyl over sustained release oral morphine (LoE 1a) [6]. A randomized controlled trial in bone metastases favoured the combination of two nonsteroidal anti-inflammatory drugs (NSAIDs) plus morphine (10.3 % dizziness reports) over one NSAID plus morphine (> 25 %), presumably due to lower morphine need in two NSAIDs (LoE 1b) [7]. Finally, both hydromorphone and morphine had at least 15 % of dizziness reports in a systematic review (LoE 1a) [8]. Conclusions: There is level of evidence 1a to 1b that immediate release oxycodone, transmucosal or intranasal fentanyl are associated with the lowest incidence of dizziness. For long-acting analgesia, transdermal fentanyl is a promising option.

Efficacy and Safety of High-Dose Controlled-Release Oxycodone in the Treatment of Moderate to Severe Pain in Patients with Advanced Cancer: A Retrospective Study

BackgroundOpioid analgesics are used to relieve pain in patients with cancer and can improve their quality of life. This study aimed to investigate the efficacy and tolerability of high-dose (>150 mg/day) controlled-release oxycodone for the control of pain in patients with advanced solid malignant tumors.Material/MethodsA retrospective clinical study was undertaken to include patients with advanced cancer treated at the Zhejiang Cancer Hospital who had treatment that included high-dose controlled-release oxycodone. The subjective numeric rating scale (NRS) for assessment of pain intensity (scores between 0–10) was used in all cases.ResultsThe study included 131 patients with advanced solid tumors with moderate to severe cancer pain. The mean NRS score before commencing high-dose controlled-release oxycodone was 7.10. The effective rate of relief pain was achieved in 90.1% (118/131) of patients, with an average effective dose of controlled-release oxycodone of 177.18±11.71 mg/day, resulting in a mean NRS of 2.15. There were 51 patients who achieved pain relief with mean treatment duration of 49.98±11.71 days. Combination therapy was required in 79 patients. Additional drugs included gabapentin (43 patients), pregabalin (10 patients) and non-steroidal anti-inflammatory drugs (NSAIDS) (26 patients). The main side effects of high-dose controlled-release oxycodone included constipation, nausea, vomiting, dysuria, dizziness, and drowsiness, but no patients discontinued treatment because of these.ConclusionsThis study showed that high-dose controlled-release oxycodone could effectively relieve moderate to severe cancer pain, without side effects that were severe enough to result in discontinuation of treatment.

Efficacy and safety of tapentadol prolonged release formulation in the treatment of elderly patients with moderate-to-severe chronic osteoarthritis knee pain: a pooled analysis of two double-blind, randomized, placebo-, and active-controlled trials

Objective: To compare efficacy and safety of tapentadol prolonged release (PR) vs oxycodone controlled release (CR) in younger patients (<65 years of age) and in elderly patients (≥65 and ≥75 years of age) in the treatment of moderate-to-severe chronic osteoarthritis (OA) knee pain.Methods: Data from two double-blind, randomized, placebo-, and oxycodone CR-controlled phase 3 trials were pooled and stratified by age. Primary efficacy end-points were change from baseline in average pain intensity at week 12 (US end-point) and over the entire maintenance period (non-US end-point).Results: A total of 1357 patients <65 years, 653 patients ≥65 years, and 176 patients ≥75 years of age were assessed. The comparison between tapentadol PR and oxycodone CR showed numerically better pain relief under tapentadol PR for both primary end-points in all three age groups. More favorable improvements were also observed for patient global impression of change, the Short Form-36 physical component score, and EuroQoL-5Dimensions health status index. In the elderly, incidences of dizziness and somnolence were comparable between active treatments, but incidences of nausea, vomiting, and constipation were considerably lower under tapentadol PR. Treatment completion rates were lowest under oxycodone CR; > 50% of elderly oxycodone CR patients named side-effects as the main reason for discontinuation.Conclusions: Tapentadol PR was effective in the treatment of moderate-to-severe chronic OA pain in elderly and younger patients. Compared to oxycodone CR, the overall and the gastrointestinal tolerability profile in particular were better in all tapentadol PR groups, regardless of age.

Person-level changes in oxycodone use after the introduction of a tamper-resistant formulation in Australia.

Australia introduced tamper-resistant controlled-release (CR) oxycodone in April 2014. We quantified the impact of the reformulation on dispensing, switching and poisonings. We performed interrupted time-series analyses using population-representative national dispensing data from 2012 to 2016. We measured dispensing of oxycodone CR (≥ 10 mg), discontinuation of use of strong opioids and switching to other strong opioids after the reformulation compared with a historical control period. Similarly, we compared calls about intentional opioid poisoning using data from a regional poisons information centre. After the reformulation, dispensing decreased for 10-30 mg (total level shift -11.1%, 95% confidence interval [CI], -17.2% to -4.6%) and 40-80 mg oxycodone CR (total level shift -31.5%, 95% CI -37.5% to -24.9%) in participants less than 65 years of age but was unchanged in people 65 years of age or older. Compared with the previous year, discontinuation of use of strong opioids did not increase (adjusted hazard ratio [HR] 0.95, 95% CI 0.91 to 1.00), but switching to oxycodone/naloxone did increase (adjusted HR 1.54, 95% CI 1.32 to 1.79). Switching to morphine varied by age (p < 0.001), and the greatest increase was in participants less than 45 years of age (adjusted HR 4.33, 95% CI 2.13 to 8.80). Participants switching after the reformulation were more likely to be dispensed a tablet strength of 40 mg or more (adjusted odds ratio [OR] 1.40, 95% CI 1.09 to 1.79). Calls for intentional poisoning that involved oxycodone taken orally increased immediately after the reformulation (incidence rate ratio (IRR) 1.31, 95% CI 1.05-1.64), but there was no change for injected oxycodone. The reformulation had a greater impact on opioid access patterns of people less than 65 years of age who were using higher strengths of oxycodone CR. This group has been identified as having an increased risk of problematic opioid use and warrants closer monitoring in clinical practice.

Oxymorphone and oxymorphone extended release: A pharmacotherapeutic review

The treatment of chronic pain remains an enormous challenge in the United States. Opioid analgesics are an important component of pharmacotherapy for chronic pain and have proven efficacy in the management of cancer and noncancer chronic pain. The newest addition to oral opioid pharmacotherapy is oral oxymorphone, a semisynthetic opioid agonist that is now available in oral immediate-release (IR) and extended-release (ER) formulations. This review discusses the pharmacology, pharmacokinetics, pharmacodynamics, pharmacotherapeutics, and clinical use of oral oxymorphone IR and ER formulations for the management of moderate to severe pain for different types of patients in a variety of settings. Two published studies evaluated the efficacy and safety of oxymorphone IR in patients with moderate to severe postoperative pain and demonstrated that it provides rapid and effective analgesia and is generally well tolerated. Six published randomized controlled trials and three published open-label studies evaluated the efficacy and safety of oxymorphone ER for chronic cancer or noncancer pain. These trials found analgesic efficacy and tolerability comparable to that provided by morphine controlled release (CR) or oxycodone CR; treatment effects with oxymorphone ER were durable for treatment periods of 12 weeks at the same dose or up to 1 year with little dose escalation. Titrated doses of oxymorphone ER were effective and generally well tolerated in both opioid-experienced and opioid-naïve patients. Aspects of oxymorphone metabolism and limited protein binding may simplify treatment in certain populations.

The effect of a potentially tamper-resistant oxycodone formulation on opioid use and harm: main findings of the National Opioid Medications Abuse Deterrence (NOMAD) study

Escalation of pharmaceutical opioid use and harm in North America is well-documented, with similar issues emerging in Australia. One response is the development of tamper-resistant formulations of opioids. A potentially tamper-resistant formulation of controlled-release oxycodone was introduced in Australia in April, 2014, rapidly replacing the non-tamper-resistant formulation. Our study is the most systematic and comprehensive examination of the impact of a new opioid formulation to date, assessing the effect of tamper-resistant formulation of controlled-release oxycodone on population-level opioid use and opioid-related harm (ie, overdose, help-seeking, and treatment-seeking); and opioid use, tampering, and preference for the tamper-resistant formulation of controlled-release oxycodone compared with other drugs or formulations among sentinel populations likely to tamper with pharmaceutical opioids. We conducted interrupted time-series analyses of opioid sales data and multiple routinely collected health datasets, followed up a cohort of people who tamper with pharmaceutical opioids before and after the introduction of the tamper-resistant formulation of controlled-release oxycodone, and analysed annual surveys of people who inject drugs. Data were collected from several Australian states: New South Wales, South Australia, and Tasmania. Meta-analyses (weighted Z tests) were conducted to synthesise across data sources providing evidence for a given indicator. At the population level, we found reduced sales of higher strengths of controlled-release oxycodone and increased sales of other oxycodone formulations. No significant effect was observed among population-level indicators of opioid overdose, or help or treatment-seeking. Mortality data were not available for inclusion at the time of our study. Meta-analyses across sentinel populations (ie, prospective cohort, surveys of people who inject drugs, and clients of supervised injecting facilities or needle and syringe programmes) indicated reduced controlled-release oxycodone use via tampering (mainly injection), with no evidence of switching to heroin or other drug use. This formulation of controlled-release oxycodone reduced tampering with pharmaceutical opioids among people who inject drugs, but did not affect population-level opioid use or harm. Mundipharma Australia, the Australian Government, and the National Health and Medical Research Council.

Survival difference associated with controlled-release oxycodone analgesic therapy for oxaliplatin-induced peripheral neuropathy in advanced colorectal cancer patients

Survival difference associated with controlled-release oxycodone analgesic therapy for oxaliplatin-induced peripheral neuropathy in advanced colorectal cancer patients

Increasing availability of illicit and prescription opioids among people who inject drugs in a Canadian setting, 2010–2014

ABSTRACTBackground: Nonmedical use of prescription opioid and illicit opioid has been increasing at an alarming rate in North America over the past decade. Objective: We sought to examine the temporal trends and correlates of the availability of illicit and prescription opioids among people who inject drugs (PWID) in Vancouver, Canada. Methods: Data were derived from three prospective cohort studies of PWID in Vancouver between 2010 and 2014. In semiannual interviews, participants reported the availability of five sets of illicit and prescription opioids: (1) heroin; (2) Percocet (oxycodone/acetaminophen), Vicodin (hydrocodone/acetaminophen), or Demerol (meperidine); (3) Dilaudid (hydromorphone); (4) Morphine; (5) oxycontin/OxyNEO (controlled-release oxycodone). We defined perceived availability as immediate (e.g., available within 10 minutes) versus no availability/available after 10 minutes. The trend and correlation of immediate availability were identified by multivariable generalized estimating equations logistic regression. Results: Among 1584 participants, of which 564 (35.6%) were female, the immediate availability of all illicit and prescribed opioids (except for oxycontin/OxyNEO) increased over time, independent of potential confounders. The Adjusted Odds Ratios of immediate availability associated with every calendar year increase were between 1.09 (95% confidence interval 1.05–1.12) (morphine and Dilaudid) and 1.13 (95% confidence interval 1.09–1.17) (Percocet/Vicodin/Demerol) (all p-values <0.05). Conclusion: The availability of most prescription opioids had continued to increase in recent years among our sample of PWID in Vancouver. Concurrent increases in the availability of heroin were also observed, raising concerns regarding combination of both illicit and prescription opioid use among PWID that could potentially increase the risk of overdose.

How does controlled-release oxycodone compare with immediate-release oxycodone or controlled-release morphine for people with cancer-related pain?

How does controlled-release oxycodone compare with immediate-release oxycodone or controlled-release morphine for people with cancer-related pain?

Efficacy and safety of controlled-release oxycodone/naloxone versus controlled-release oxycodone in Korean patients with cancer-related pain: a randomized controlled trial

BackgroundControlled-release oxycodone/naloxone (OXN-CR) maintains the effect of opioid-induced analgesia through oxycodone while reducing the occurrence rate of opioid-induced constipation through naloxone. The present study was designed to assess the non-inferiority of OXN-CR to controlled-release oxycodone (OX-CR) for the control of cancer-related pain in Korean patients.MethodsIn this randomized, open-labeled, parallel-group, phase IV study, we enrolled patients aged 20 years or older with moderate to severe cancer-related pain [numeric rating scale (NRS) pain score ≥4] from seven Korean oncology/hematology centers. Patients in the intention-to-treat (ITT) population were randomized (1:1) to OXN-CR or OX-CR groups. OXN-CR was administered starting at 20 mg/10 mg per day and up-titrated to a maximum of 80 mg/40 mg per day for 4 weeks, and OX-CR was administered starting at 20 mg/day and up-titrated to a maximum of 80 mg/day for 4 weeks. The primary efficacy endpoint was the change in NRS pain score from baseline to week 4, with non-inferiority margin of −1.5. Secondary endpoints included analgesic rescue medication intake, patient-reported change in bowel habits, laxative intake, quality of life (QoL), and safety assessments.ResultsOf the ITT population comprising 128 patients, 7 with missing primary efficacy data and 4 who violated the eligibility criteria were excluded from the efficacy analysis. At week 4, the mean change in NRS pain scores was not significantly different between the OXN-CR group (n = 58) and the OX-CR group (n = 59) (−1.586 vs. −1.559, P = 0.948). The lower limit of the one-sided 95% confidence interval (−0.776 to 0.830) for the difference exceeded the non-inferiority margin (P < 0.001). The OXN-CR and OX-CR groups did not differ significantly in terms of analgesic rescue medication intake, change in bowel habits, laxative intake, QoL, and safety assessments.ConclusionsOXN-CR was non-inferior to OX-CR in terms of pain reduction after 4 weeks of treatment and had a similar safety profile. Studies in larger populations of Korean patients with cancer-related pain are needed to further investigate the effectiveness of OXN-CR for long-term pain control and constipation alleviation.Trial registration ClinicalTrials.gov NCT01313780, registered March 8, 2011

Nurse practitioner led pain management the day after caesarean section: A randomised controlled trial and follow-up study

BackgroundPain on the day after caesarean section is often treated with controlled-release oxycodone to supplement the decline in analgesia from intrathecal opioids. Evidence suggests that caesarean birth is a biopsychosocial experience where a comprehensive approach is needed that promotes control and participation in pain management. ObjectivesThis study compared immediate-release oxycodone integrated with supportive educational strategies to controlled-release oxycodone. A follow-up phase aimed to explore pain over three months. DesignThis study was a two-group parallel randomised controlled trial. SettingA metropolitan hospital in Australia with a birthing suite, operating rooms, and a postnatal unit. ParticipantsEnglish-speaking women scheduled for elective caesarean section were mailed trial information. Exclusion criteria included contraindications to intrathecal analgesia, herpes simplex infection, a history of chronic pain, opioid tolerance, or substance abuse. A total of 131 participants were recruited and randomised out of 298 eligible participants. MethodsGroup allocation was undertaken using sequentially numbered opaque sealed envelopes. The nurse practitioner intervention commenced on the day after surgery with immediate-release oxycodone alongside supportive strategies. The control group received scheduled doses of controlled-release oxycodone. All participants could request additional oxycodone or tramadol. Primary outcomes were pain intensity and secondary outcomes included patient global impression of change, pain interference, opioid consumption, and maternal perception of control. A follow-up phase evaluated pain outcomes over three months. ResultsThe final sample size was 122, with 61 participants in each group. Pain intensity scores were analysed by linear mixed regression models. There were no statistical differences over 24h between the control and intervention groups at rest (p=0.40, 95% CI – 4.8mm, 11.9mm) or on sitting or moving (p=0.561, 95% CI –15.2mm, 8.3mm). Patient global impression of change was significant over three hours (p=0.014, OR=2.5, 95% CI 1.2, 5.3). The intervention group reported less pain interference while consuming less oxycodone (p<0.05). There was no difference between groups in terms of perceived control over pain management (p=0.273, 95% CI –16.2mm, 4.6mm). The follow-up analysis graded 5.9% of participants as experiencing severe pain interference. Chronic pain following caesarean was associated with postnatal depression (p<0.001). ConclusionsThe research showed that a nurse practitioner intervention can improve pain management following caesarean section. The results underscore the influence of biological, psychological, and social factors on acute pain. Hence, this study reinforces the need for a biopsychosocial approach to acute pain management following caesarean delivery.

Oxycodone for cancer-related pain.

Oxycodone for cancer-related pain.

Efficacy and safety of tapentadol prolonged release for moderate-to-severe chronic osteoarthritis knee pain: a pooled analysis of two double-blind, randomized, placebo- and oxycodone controlled release-controlled studies

Objective: To compare efficacy and safety of tapentadol prolonged-release (PR) and oxycodone-controlled release (CR) in moderate-to-severe chronic osteoarthritis knee pain.Methods: Data from two double-blind, randomized, placebo- and oxycodone CR-controlled phase 3 studies with a 3-week titration period and 12-week controlled dose adjustment maintenance period were pooled. Primary efficacy end-points were change from baseline in average pain intensity at week 12 (US end-point) and over the entire maintenance period (non-US end-point).Results: A total of 2,010 patients were assessed. For both primary end-points, tapentadol PR was significantly more effective than oxycodone CR (LS mean difference of –0.41 [95% CI = –0.65, –0.16; p = 0.001] at week 12 and –0.35 [95% CI = –0.58, –0.12; p = 0.003] over 12 weeks of maintenance [last observation carried forward]). Significantly better outcomes than for oxycodone CR were also observed for patient global impression of change, both Short Form-36 component scores, and EuroQoL-5Dimensions health status index (all p < 0.001). Relative risk for vomiting, constipation, nausea, somnolence, and pruritus was lower for tapentadol PR than for oxycodone CR. A higher proportion of oxycodone CR patients discontinued treatment (64% vs 42.2% for tapentadol PR); time to treatment discontinuation due to an adverse event was significantly shorter for oxycodone CR (p < 0.001).Conclusions: The analyses suggest that tapentadol PR provided superior pain relief and a more improved overall health status than oxycodone CR in a large patient population with moderate-to-severe chronic osteoarthritis pain. Compared to oxycodone CR, tapentadol PR showed a more favorable tolerability profile with better gastrointestinal tolerability.

Controlled-release oxycodone improves pain management after uterine artery embolisation for symptomatic fibroids

To evaluate if pre- and post-procedure administration of controlled-release oxycodone (CRO) in combination with standard analgesia improves pain control and decreases the amount of required post-procedure opioids in uterine fibroid embolisation (UFE). Between January 2009 and March 2010, 60 consecutive women were prospectively randomised in two groups for UFE: the control group, in which 30 patients underwent the standard anaesthetic procedure and the CRO group, in which 30 patients underwent the standard anaesthetic procedure with the addition of CRO. Age, pain, nausea/vomiting, fibroid volume, length of hospital stay, and use and dose of morphine received via the patient-controlled analgesia (PCA) device in both groups were evaluated to compare the two methods of pain control. Fibroid volume as measured at magnetic resonance imaging (MRI) was evaluated for correlation with post-embolisation pelvic pain over a period of 24 hours. A significant difference was seen in the pain scores at 24 hours (p=0.029), with less pain in the CRO group. More patients from the control group required morphine (p=0.017), and at higher levels (p=0.130). Pruritus was lower in patients of the CRO group, probably because they received less morphine (p=0.029). No correlation was seen between leiomyoma volume and pain levels over 24 hours (Spearman's ρ=0.02; p=0.881). Length of hospital stay was not different between the two groups. The addition of CRO to standard analgesia for UFE provides more effective analgesia, with a reduction in pain scores in 24 hours, less morphine use, and decreased side effects, mainly pruritus.

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

IntroductionOpioids 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.MethodsA 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.ResultsAt 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.ConclusionIn 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).

The Influence of Type of Anesthesia, Perioperative Pain, and Preoperative Health Status on Chronic Pain Six Months After Thoracotomy—A Prospective Cohort Study

Chronic post-thoracotomy pain (CPP) has a high incidence. However, less is known about risk factors and the influence of different analgesia therapies. In this prospective cohort study, patients either received standardized epidural analgesia or began an oral analgesic protocol with controlled-release oxycodone immediately postoperatively. Patients answered a baseline questionnaire on the day before surgery and a follow-up questionnaire six months postoperatively. The questionnaire included Short-Form 12, the Neuropathic Pain Scale, and descriptive questions for CPP. Pain protocols of all patients were examined. Logistic regression was used to analyze the risk factors related to CPP. One hundred seventy-four patients were enrolled; data of 131 patients were available after the six-month follow-up period. Fifty-one patients (39%) had CPP six months postoperatively. Of these, more than 80% had impaired daily activity or ability to work, or reported sleeping disturbance due to CPP. The strongest predictive factors for the development of CPP were: thoracic pain for three months preoperatively (odds ratio [OR] = 3.54, 95% confidence interval [CI] = 1.69-7.40, P = 0.001), thoracic pain for 12 months preoperatively (OR = 2.73, 95% CI = 1.28-5.83, P = 0.009), and higher pain scores at rest in the first five postoperative days compared with patients without CPP (OR = 1.79, 95% CI = 1.24-2.57, P = 0.002). Neuropathic pain was present in 4.8% of patients. Patients with CPP had a reduced physical (P = 0.005) and mental health status (P = 0.03) six months after surgery compared with patients without CPP. Preoperative thoracic pain and higher pain scores in the first five postoperative days seem to be the strongest risk factors for the development of CPP. CPP patients reported poorer mental and physical health before and six months after surgery.

Dialyzability of Oxycodone and Its Metabolites in Chronic Noncancer Pain Patients with End-Stage Renal Disease.

Opioids are the preferred analgesic drugs to treat severe chronic pain conditions among dialysis patients; however, knowledge about their dialyzability features is limited. Oxycodone is increasingly used for the treatment of chronic pain conditions as oral controlled release (CR) tablets; however, evidence about this drug and its metabolites' dialyzability is lacking. We assessed, during 4-hour dialysis sessions, the effect of standard hemodialysis (HD) and online hemodiafiltration (HDF) methods on the plasma concentration of oxycodone and its metabolites in n = 20 chronic pain patients with end-stage renal disease who were stably treated with oral CR oxycodone. Chromatographic techniques were used to evaluate the studied compounds' plasma concentrations at three different time points during dialysis. Mean plasma concentrations of oxycodone and noroxycodone in the sample showed an overall reduction trend over time, but it was less enhanced for noroxycodone. Mean reduction in oxycodone and noroxycodone arterial concentrations was significant and higher with HDF (54% and 27%, respectively) than with HD (22% and 17%, respectively). Analysis of the regression of these compounds' clearance on their increasing arterial concentration showed a more stable and linear clearance prediction with HDF (roughly 85 mL/min); with HD, for increasing arterial concentration, clearance of oxycodone decreased while noroxycodone clearance increased. While no oxymorphone or noroxymorphone metabolites were detected, limited dialyzability of oxycodone and noroxycodone was documented along with insignificant postdialysis pain increment. This evidence will contribute toward considerations as to the safety of the use of oxycodone in dialysis patients in the future.

Patient-relevant outcomes and health-related quality of life in patients with chronic, severe, noncancer pain treated with tapentadol prolonged release-Using criteria of health technology assessment.

To perform a systematic comparison of tapentadol prolonged release (PR) and oxycodone controlled release (CR) using patient-relevant endpoints of efficacy, safety, and health-related quality of life (HRQoL) according to criteria used in health technology assessment. To derive a minimal important difference (MID) for the EQ-5D from three pivotal trials to measure patient-relevant changes in HRQoL. Randomized, double-blind, placebo and active controlled. Outpatient primary care. Patients with severe chronic osteoarthritis pain (two pivotal studies) and severe lower-back pain (one pivotal study) were enrolled. The intent-to-treat population of the three studies comprised a total of 2,968 patients (tapentadol PR arms: 978, oxycodone CR arms: 999, and in the placebo arms: 991). Tapentadol PR (100-250 mg bid), oxydodone CR (20-50 mg bid), or placebo over a period of 15 weeks (3 weeks titration plus 12 weeks maintenance). Patient-relevant endpoints of efficacy, safety, tolerability, and HRQoL. Tapentadol PR demonstrated significant added benefits as compared to oxycodone CR in meta-analyses of the patient-relevant outcomes 30 percent pain relief (Realtive risk [RR]: 0.80 [0.75, 0.87]), treatment discontinuations (RR: 0.55 [0.363, 0.825]), safety (RR: 0.652 [0.599, 0.710]), and HRQoL (RR: 0.78 [0.64, 0.96]) based on a MID derived for the EQ-5D summary index. Added benefit of tapentadol in all endpoint categories suggests that it may be beneficial to initiate treatment of chronic severe nonmalignant pain with tapentadol rather than oxycodone.

Assessing the impact of prescribing directives on opioid prescribing practices among Veterans Health Administration providers.

The study aimed to test whether directives on opioid prescribing released by the Veterans Health Administration (VHA) or the Food and Drug Administration (FDA) had an impact on prescribing among VHA providers. We used the VHA's linked pharmacy and patient medical records database to identify new prescriptions written for propoxyphene, fentanyl, and controlled release (CR) oxycodone between 1/1/2000 and 12/31/2009. We plotted the monthly proportion of these prescriptions that complied with components of four specific safety alerts or directives for these substances issued by the VHA or FDA between 1/1/2001 and 12/31/2008. We modeled compliance using interrupted time series analysis and a generalized additive model with the addition of an indicator variable to flag prescriptions that followed the directive's release date. A total of 32.2 million new prescriptions for fentanyl, oxycodone CR, and propoxyphene were written for VHA patients meeting inclusion criteria. Compliance with guidelines in the directives increased steadily throughout the entire study period, with no clinically meaningful inflection point near the date of each directive's release. Generalized additive modeling and interrupted time series analysis found that the indicator flag slightly improved the fit of the data, but visual inspection of the plots revealed no change at a level of practical significance. While prescribing compliance increased throughout the period, release of FDA and VHA alerts and guidelines did not appear to contribute to this change. Given the fivefold increase in the rate of drug-related overdose deaths since 1990, identifying effective methods to communicate safety messages and change prescriber behavior remains a priority for future work. Copyright © 2016 John Wiley & Sons, Ltd.

OPAL: a randomised, placebo-controlled trial of opioid analgesia for the reduction of pain severity in people with acute spinal pain. Trial protocol

IntroductionLow back pain and neck pain are extremely prevalent and are responsible for an enormous burden of disease globally. Strong analgesics, such as opioid analgesics, are recommended by clinical guidelines...