Oxycodone IR Research Articles

Oxycodone for cancer-related pain.

Oxycodone for cancer-related pain.

Comparison of opioid prescribing upon hospital discharge in patients receiving tapentadol versus oxycodone following orthopaedic surgery.

Background The changing of opioids during the transition of care from hospital to home may be associated with harm. Objective To compare patients receiving tapentadol IR versus oxycodone IR following orthopaedic surgery during hospitalisation with regard to the changing of opioids at hospital discharge. Setting A major metropolitan tertiary referral hospital in Australia. Methods This is a retrospective cohort study. Participants included adult orthopaedic surgery patients receiving postoperative tapentadol IR or oxycodone IR during hospitalisation between 1 January 2018 and 30 June 2019. Main outcome measure The proportion of patients for whom the opioid prescribed was changed at hospital discharge. Results The study cohort included 199 patients. Of these, 100 patients received oxycodone and 99 patients received tapentadol post-operatively during hospitalisation. The mean age was 66years (SD, 12years) and 111 (56%) were female. The most common surgeries were total knee arthroplasty (91, 46%), total hip arthroplasty (63, 32%) and shoulder surgery (26, 13%). Patients in the tapentadol group were more likely to be changed to a different opioid upon hospital discharge than the oxycodone group (57% versus 9%, difference 48% [95% CI 36-59%, p < 0.01). After adjusting for confounders, post-operative tapentadol use was more likely to be associated with opioid changing upon discharge (OR 16.5, 95% CI 6.7 to 40.8, p < 0.01). Conclusions The post-operative use of tapentadol IR during hospitalisation was associated with an increased likelihood of opioid changing at hospital discharge. This practice could have patient safety implications.

Nonmedical Use of Xtampza® ER and Other Oxycodone Medications in Adults Evaluated for Substance Abuse Treatment: Real-World Data from the Addiction Severity Index-Multimedia Version (ASI-MV®).

PurposeThe purpose of this study was to evaluate real-world data related to past 30-day nonmedical use (NMU) and routes of administration of Xtampza® ER and comparator oxycodone medications in the US as captured within the Addiction Severity Index-Multimedia Version® (ASI-MV®).MethodsData were collected from July 2016 through December 2019 from 647 centers located in 44 states using the ASI-MV, a clinical instrument used to evaluate substance use and treatment planning. Demographic characteristics were assessed using Pearson’s chi-square test for categorical data and quarterly NMU rates were calculated. Distribution of route of administration was studied using a proportional reporting ratio (PRR) analysis.ResultsOf 192,810 assessments, 42,279 (21.9%) indicated past 30-day NMU of at least one prescription opioid, including Xtampza ER (N=73, 0.2%), other oxycodone ER (n=3802, 9.0%) and oxycodone IR (n=14,579, 34.5%). All quarterly Xtampza ER NMU rates per 100 ASI-MV assessments were significantly lower than those for other oxycodone ER and oxycodone IR. Overall, quarterly Xtampza ER NMU drug utilization adjusted rates were significantly lower than quarterly rates observed for other oxycodone ER NMU but not consistently significantly lower than oxycodone IR NMU. Although not all statistically significant, all ratios from the PRR analysis were less than 1.0, indicating that rates of use of any alternate route, any non-oral route, snorting, and injecting were higher for other oxycodone ER and oxycodone IR than for Xtampza ER.ConclusionXtampza ER had significantly lower rates of NMU than other oxycodone ER products and oxycodone IR products, as well as significantly lower rates of non-oral NMU than oxycodone IR products, in a population of individuals seeking substance abuse treatment. Understanding risks associated with different opioid medications is important for prescribers as they manage risks of opioid misuse and abuse with effective pain therapy.

Multimodal oral analgesia strategy after ambulatory arthroscopic shoulder surgery: case series using adaptive therapeutic approaches by sequential analysis

Pain control and quality of recovery (QoR) at home remains a challenge after ambulatory shoulder arthroscopy. This study aims to assess the QoR and pain relief using a sequential implementation strategy for rescue analgesic drugs. After institutional review board approval, patients (>18 years, American Society of Anesthesiology [ASA] score 1-3 stable) scheduled for ambulatory surgery under general anesthesia with a single-shot interscalene nerve block were enrolled. After discharge, patients received standard information regarding the postoperative recovery and care consisting of a multimodal analgesic regime (acetaminophen and ketoprofen for 5 days). The first 48 postoperative hours allowed us to compare 3 different rescue drug regimes with a control group, in sequential order: tramadol (control group), tramadol + nefopam, immediate-release oxycodone (IR), and extended-release oxycodone (ER). The primary endpoint was the QoR 40 score at 48 hours after surgery. Secondary endpoints were pain relief and adverse events over a 7-day period. An intention-to-treat statistical analysis was performed with sequential analysis (as an interim analysis) every 20 patients. Results were recorded as medians and interquartiles (25-75). We analyzed 109 patients with similar characteristics among groups. The QoR 40 scores were similar for the tramadol group (168 [161-172]), the tramadol + nefopam group (161 [151-173], P = .09), and the IR group (164 [153-169], P = .17), but higher for the ER group (176 [167-181], P = .03). Concerning adverse events, drugs were interrupted more frequently in the tramadol + nefopam group (36 %). In the ER group, a higher quality of postoperative relief was attained in the domains of pain and sleep. The present study shows that a combination of IR and ER oxycodone over a short period of time (<48 hours) is associated with a better QoR at home after ambulatory shoulder surgery.

Evaluation of the Efficacy of Liposomal Bupivacaine in Total Joint Arthroplasty

Background: Appropriate pain control is one of the cornerstones necessary to promote positive clinical outcomes. A new bupivacaine liposomal formulation was designed to extend its analgesic effect for up to 72-hours post-surgery, reportedly leading to significant opioid-sparing. Method: Retrospective and prospective chart review conducted in a 178-bed academic institution between January 2013 to December 2013 and August 2014 to November 2014, in 115 patients that receive hip and knee arthroplasty. The primary outcome was the measurement of average daily pain score on post-operative days 1 and 2. Secondary outcomes included length of stay, overall opioid use post-surgery and pain control satisfaction using Press-Ganey® scores. Results: The average pain scores in the HCl group were 4.64 and 4.38 (Likert score: 0-10) for POD 1 and POD 2, compared to 4.72 POD 1 and 4.2 POD 2 in the liposome group (POD 1: p = 0.413; POD 2: p = 0.303). The difference in LOS for knee arthroplasty was statistically significant [HCl group: 1.94 days (± 0.66) versus liposome group: 2.27 days (±0.77) p-value = 0.038)] favoring the standard of care. For hip arthroplasty or bilateral knee arthroplasty the differences in LOS were not statistically significant (p = 0.052 and p = 0.484 respectively). 93% of the patients in the HCl group, pain was well controlled, versus 88.5% in the liposome group with similar oxycodone IR use among groups. Conclusion: Liposome bupivacaine did not offer a notable benefit compared to the HCl formulation in our study.

A Goal-directed Quality Improvement Initiative to Reduce Opioid Prescriptions After Orthopaedic Procedures.

Introduction:Orthopaedic surgeons are increasingly aware of deleterious effects of the opioid epidemic and the association between overprescription and diversion toward nonmedical opioid use or substance abuse. Opiate prescriptions at the time of hospital discharge have been identified as target for intervention. This study describes the successful outcome of a goal-directed intervention aimed at decreasing opioid overprescription by providing routine feedback to providers regarding their prescribing patterns.Methods:The amount of opioid medications, quantified as oral morphine equivalents (OMEs), provided to opioid-naive adult patients on discharge after orthopaedic surgery was prospectively collected. As part of an institutional quality improvement initiative, medical providers received reports every 2 months detailing median discharge OMEs prescribed, trended over time. After 6 months, a retrospective comparison was done between preintervention and intervention patient cohorts.Results:There were 401 patients in the preintervention cohort and 429 patients in the intervention cohort. Both groups were similar in regard to age, sex, rates of depression, surgical time, length of stay, orthopaedic subspecialty, and inpatient opioid requirement before discharge. Patients in the intervention cohort were prescribed markedly fewer opioid medications by 25%, equivalent to 20 tablets of 5-mg oxycodone IR (450 versus 600 OMEs, P < 0.001). Despite these opioid medications, opioid refill rates during the first 90 days after discharge did not markedly change between groups.Discussion:It is critical to judiciously treat postoperative pain while avoiding opioid overprescription. This study demonstrated the outcome of a goal-directed initiative to decrease overprescription of opioid medications. The initiative reduced discharge opioid prescriptions yet did not increase the risk of requiring a prescription refill in the postoperative period. This indicates that such an approach can result in opioid reduction, while still providing appropriate care and pain control for patients.

Efficacy and Safety of Tapentadol Immediate Release Assessment in Treatment of Moderate to Severe Pain: A Systematic Review and Meta-Analysis.

To assess the efficacy and safety of tapentadol IR for moderate to severe pain compared to oxycodone IR. A search was carried out up to July 2015 for randomized controlled trials (RCTs) of tapentadol IR compared to placebo or oxycodone HCL IR 10 mg for moderate to severe pain. Studies were pooled by risk ratio (RR) and weighted mean differences (WMD) with 95% confidence interval (CI). Nine RCTs (n = 3,961) were analyzed. In this meta-analysis, tapentadol IR (50-, 75-, and 100-mg doses) showed significant improvements in moderate to severe pain relief on the sum of pain intensity difference over 48 hours (SPID 48 ) scores ( P < 0.00001 or P = 0.01). No statistically significant difference among all three doses of tapentadol IR and oxycodone HCL IR 10 mg on both SPID 48 and total pain relief over 48 hours (TOTPAR 48 ) scores (all P > 0.05) was found. Compared with tapentadol IR 50 mg, tapentadol IR 75 mg demonstrated significant improvement in moderate to severe pain relief based on both SPID 48 and TOTPAR 48 scores (all P < 0.05). For total adverse events (AEs) incidence, tapentadol IR 50 and 75 mg were significantly lower than oxycodone HCL IR 10 mg. Incidence of nausea and constipation were significantly lower with either tapentadol IR 50 or 75 mg compared with oxycodone HCL IR 10 mg (all P < 0.05). Tapentadol IR 75 mg might be an optimal dose for moderate to severe pain control with fewer side effects. All three doses of tapentadol IR could provide comparable efficacy to oxycodone HCL IR 10 mg.

In vitro assessment of the potential for abuse via the intravenous route of oxycodone DETERx® microspheres.

Abuse of prescription analgesics is a well-recognized problem, with nearly 2 million people aged 12 years or older initiating nonmedical use of pain relievers in 2012. The prevalence of opioid abuse via intravenous (IV) injection has led to the development of dosage forms designed to deter abuse using different inactive ingredients and formulation strategies. This study evaluated the IV abuse potential for a novel, microsphere-encapsulated abuse-deterrent formulation of oxycodone, Xtampza™ ER (referred to as "oxycodone DETERx"). The extraction of oxycodone DETERx and two comparators, extended-release oxycodone (oxycodone ER) and immediate-release oxycodone (oxycodone IR), was evaluated in small volumes (5 and 10 mL) of water after manipulation of the dosage forms. The syringeability and injectability of these products were evaluated to determine the feasibility of using these products via IV injection. The extraction of oxycodone from oxycodone DETERx was nominal, with <12 percent extracted under any test condition. Oxycodone ER and oxycodone IR had as much as 83 and 98 percent oxycodone extracted, respectively. Injectability and syringeability analyses showed that injection of oxycodone DETERx microspheres in suspension is not feasible. In contrast, oxycodone ER and oxycodone IR suspensions were more easily drawn into and expelled from a syringe. Furthermore, injection of molten oxycodone DETERx microspheres was also shown to be ineffective. The chemical and physical properties of oxycodone DETERx provide barriers to manipulating the microspheres for the purpose of IV injection.

Oxycodone Immediate Release for Cancer Pain Management in Turkey: Maximizing Value in Opioid Analgesics

Cancer pain can be severe, yet is often undertreated. In many parts of the world, there is a reluctance to prescribe narcotics for analgesia. Since the World Health Organization first published its pain ladder treatment paradigm in 1988, cancer pain is usually treated initially with nonopioids, then weak opioids, and finally strong opioids along with adjuvant agents as the pain intensifies. When initiating opioid therapy for cancer patients, the clinician must consider whether the patient is opioid naƒ¯ve or opioid experienced. For naƒ¯ve patients, opioid therapy must be started slowly, at a low dose initially, with adverse events anticipated and treated proactively. In all cases, opioid titration involves a controlled, stepwise increase of opioid dose until adequate (but not necessarily 100%) analgesia is achieved. A variety of opioid products are available, including immediate-release and controlled-release formulations. Immediate-releaseformulations are designed for easy titration to adequate analgesia; their rapid onset of action also makes them appropriate for managing breakthrough pain. Although morphine has long been considered the gold standard of cancer analgesics, oral oxycodone is increasingly used and is similar to morphine in efficacy and safety for cancer patients. Indeed, about 75% of morphine-tolerant patients can be successfully rotated to oxycodone. Adverse events with oxycodone are similar or perhaps favorable compared to those of other strong opioids. Because cancer pain can be challenging to treat, the addition of oral oxycodone IR is an important new tool for clinicians to consider when trying to control cancer pain.

The impact of a reformulation of extended-release oxycodone designed to deter abuse in a sample of prescription opioid abusers

BackgroundPrescription opioid abuse is a significant public health concern that requires strategies to reduce its impact, including development of abuse deterrent formulations. OxyContin®, an extended-release oxycodone (ERO) formulation, has been widely abused. This study assessed the effects of reformulated ERO, designed to be more difficult to manipulate for purposes of intranasal and intravenous abuse, on patterns of opioid abuse among a sample of individuals from rural Appalachia with a history of ERO abuse. MethodsStructured interviews assessing opioid abuse (past 30-day abuse and retrospectively reported abuse prior to the reformulation in August 2010) were completed by 189 individuals between December 2010 and September 2011. ResultsThe past 30-day prevalence and frequency of reformulated ERO abuse through any route (33%, 1.9 days/month), snorting (5%, 0.2 days/month), and injecting (0.5%, <0.1 days/month) were low and infrequent compared to that of IR oxycodone (any route: 96%, 19.5 days/month; snorting: 70%, 10.3 days/month; injecting: 51%, 10.5 days/month) and retrospectively reported abuse of original ERO in August 2010 (any route: 74%, 13.4 days/month; snorting: 39%, 6.0 days/month; injecting: 41%, 8.6 days/month). After the reformulation, the prevalence of original ERO abuse significantly declined while abuse of reformulated ERO remained steadily low. Heroin abuse was rare in this sample. ConclusionsIn this sample, abuse of reformulated ERO was low, and lower than abuse of original ERO retrospectively and IR oxycodone concurrently, particularly through injecting and snorting routes of administration. There was no evidence to suggest that reformulated ERO became a substitute for original ERO.

Response to Letter by Dr. Ruan

The authors of the article titled “The abuse potential of Remoxy®, an extended-release formulation of oxycodone, compared with immediate- and extended-release oxycodone” would like to thank Dr. Ruan for his interest in the article and thoughtful comments in his letter to the editor. The authors would also like to thank the editor for the opportunity to address these points. In the letter to the editor, Dr. Ruan raises three points regarding the article: 1) comparing Remoxy, oxycodone ER, and oxycodone IR under different conditions predisposes the conclusion drawn from this study to confusion and speculation; 2) the authors incorrectly stated that Benziger et al. ⇓ noted lower bioavailability of oxycodone ER and IR in the fed state; and 3) whether including a subgroup of opioid-dependent recreational drug users would be more clinically enlightening. To clarify the first point, as Dr. Ruan notes from the introduction of the article, the abuse potential study seeks to compare treatments under conditions that recreational drug users would find most appealing to abuse. Researchers have noted that drug kinetics play an important role in drug abuse and that there are effects of rate of brain delivery …

1707 - The International Collaborative Project to Evaluate the Availability and Accessibility of Opioids for the Management of Cancer Pain: Survey Result

ABSTRACT Introduction The International Collaborative Project to Evaluate the Availability and Accessibility of Opioids for the Management of Cancer Pain has been coordinated by ESMO, EAPC, UICC, PPSG + WHO with the collaboration of regional and international palliative care and oncology societies. Aim To develop a comprehensive database on the availability and accessibility of opioid medication for the management of cancer pain in: Africa, Asia, Latin America and the Caribbean and Middle East. The adequacy of formulary availability is evaluated relative to the International Association of Hospice and Palliative Care list of Essential Medicines for Palliative Care. Overregulation is evaluated according to descriptors identified by the World Health Organization and the International Narcotics Control Board. Results Between 12/2010-7/2012, 156 reports were submitted from identified reporters in 76 countries and 19 Indian states (58% countries, 83% population). Very few countries provide all 7 opioids on the essential drug list of the IAHPC (codeine, immediate and slow release oral morphine, oral IR oxycodone and transdermal fentanyl) and in many countries less than 3/7 drugs are available. Furthermore, in most of the countries opioids are either not or are weakly subsidised by gov. and availability is often limited. Many countries have highly restrictive regulations that limit entitlement of cancer patients to receive prescriptions, limit prescriber privileges, impose restrictive limits on duration of prescription, restrict dispensing, and increase bureaucratic burden of the prescribing and dispensing process. Conclusions In many places across Africa, Asia, ME and L + C America governments are failing cancer patients in delivery of adequate pain relief. There is a need for increased availability of affordable opioids for the management of cancer pain. A priority action is examination of drug control policies and repeal of excessive restrictions which impede this most fundamental aspect of cancer care.

Randomized, Double-Blind, Placebo-Controlled Study of the Abuse Potential of Different Formulations of Oral Oxycodone

The objective of this study was to evaluate the pharmacokinetics and abuse potential of different formulations of oxycodone. The participants completed an 8-day, placebo-controlled trial with four phases: naloxone challenge, double-blind drug discrimination, double-blind abuse liability, and discontinuation. Nineteen healthy, male, recreational drug abusers participated in this study. The participants were administered different doses and formulations of oxycodone (40 mg immediate release [IR], 40 mg controlled release [CR], crushed 40 mg CR, and 80 mg CR) to evaluate pharmacokinetic parameters and ratings of drug liking and high. Pharmacokinetic parameters were determined over a 12-hour dosing interval. The primary pharmacodynamic endpoints were two questions from the Drug Effects Questionnaire ("Do you like the drug?" and "How high are you now?"). Maximal plasma concentrations and area under the curve determinations were similar for 40 mg IR, crushed 40 mg CR, and 80 mg CR, which were all greater than 40 mg CR. For drug liking and high, the maximal effect and area under the effect curve were similar for the three formulations, which were all greater than 40 mg CR. The dose required to produce comparable reports of drug liking and high was approximately twofold greater for the CR vs IR formulation. When the 40 mg CR tablet was crushed, the pharmacokinetic and pharmacodynamic profile was similar to the 40 mg IR formulation. Adverse events were consistent with opioid administration. Intact, orally administered oxycodone CR produced less drug liking and high than IR oxycodone, and required approximately twofold greater doses to produce subjective effects comparable to IR oxycodone.

Pharmacokinetic and Pharmacodynamic Modeling of Opioid-Induced Gastrointestinal Side Effects in Patients Receiving Tapentadol IR and Oxycodone IR

To understand the relationship between the risk of opioid-related gastrointestinal adverse effects (AEs) and exposure to tapentadol and oxycodone as well as its active metabolite, oxymorphone, using pharmacokinetic/pharmacodynamic models. The analysis was based on a study in patients with moderate-to-severe pain following bunionectomy. Population PK modeling was conducted to estimate population PK parameters for tapentadol, oxycodone, and oxymorphone. Time to AEs was analyzed using Cox proportional-hazards models. Risk of nausea, vomiting, and constipation significantly increased with exposure to tapentadol or oxycodone/oxymorphone. However, elevated risk per drug exposure of AEs for tapentadol was ~3-4 times lower than that of oxycodone, while elevated AE risk per drug exposure of oxycodone was ~60 times lower than that for oxymorphone, consistent with reported in vitro receptor binding affinities for these compounds. Simulations show that AE incidence following administration of tapentadol IR is lower than that following oxycodone IR intake within the investigated range of analgesic noninferiority dose ratios. This PK/PD analysis supports the clinical findings of reduced nausea, vomiting and constipation reported by patients treated with tapentadol, compared to patients treated with oxycodone.

Scale-up of opioid substitution therapy in India: Opportunities and challenges

Prescription opioid abuse is a significant public health concern that requires strategies to reduce its impact, including development of abuse deterrent formulations. OxyContin®, an extended-release oxycodone (ERO) formulation, has been widely abused. This study assessed the effects of reformulated ERO, designed to be more difficult to manipulate for purposes of intranasal and intravenous abuse, on patterns of opioid abuse among a sample of individuals from rural Appalachia with a history of ERO abuse.Structured interviews assessing opioid abuse (past 30-day abuse and retrospectively reported abuse prior to the reformulation in August 2010) were completed by 189 individuals between December 2010 and September 2011.The past 30-day prevalence and frequency of reformulated ERO abuse through any route (33%, 1.9 days/month), snorting (5%, 0.2 days/month), and injecting (0.5%, <0.1 days/month) were low and infrequent compared to that of IR oxycodone (any route: 96%, 19.5 days/month; snorting: 70%, 10.3 days/month; injecting: 51%, 10.5 days/month) and retrospectively reported abuse of original ERO in August 2010 (any route: 74%, 13.4 days/month; snorting: 39%, 6.0 days/month; injecting: 41%, 8.6 days/month). After the reformulation, the prevalence of original ERO abuse significantly declined while abuse of reformulated ERO remained steadily low. Heroin abuse was rare in this sample.In this sample, abuse of reformulated ERO was low, and lower than abuse of original ERO retrospectively and IR oxycodone concurrently, particularly through injecting and snorting routes of administration. There was no evidence to suggest that reformulated ERO became a substitute for original ERO.

Comparison of analgesic response and safety of flexible dose vs fixed low dose MoxDuo® IR (morphine plus oxycodone) in patients with moderate to severe pain following total knee arthroplasty

Comparison of analgesic response and safety of flexible dose vs fixed low dose MoxDuo® IR (morphine plus oxycodone) in patients with moderate to severe pain following total knee arthroplasty

Research and development round-up: August 2008

New results from three phase III clinical studies for the novel centrally-acting analgesic tapentadol show similar high efficacy of tapentadol immediate release tablets (IR) compared with standard opioid oxycodone IR, among patients treated for severe pain. Those taking tapentadol, however, benefited from lower incidences of side effects, particularly gastrointestinal (GI) side-effects.