-
Expert Opinion on Drug Metabolism &... Jul 2016Chronic low back pain (CLBP) is a common and difficult illness to manage. Some individuals with CLBP have pain processing disorders and are also at risk for opioid... (Review)
Review
INTRODUCTION
Chronic low back pain (CLBP) is a common and difficult illness to manage. Some individuals with CLBP have pain processing disorders and are also at risk for opioid abuse, misuse; addiction and diversion. Guidelines have been published to guide management; neuromodulation, exercise, mindfulness-based stress reduction and cognitive behavior therapies among other non-pharmacological reduce the pain of CLBP with minimal toxicity. Pharmacological management includes acetaminophen, NSAIDs and antidepressants, mainly duloxetine. Abuse-deterrent opioids have been developed which have been shown to reduce pain and opioid abuse risk. ALO-02 is a tamper-resistant sustained release opioid consisting of extended release oxycodone and sequestered naltrexone. Pivotal studies of ALO-02 have centered on patients with CLBP.
AREAS COVERED
This manuscript will review CLBP, the pivotal analgesic and clinical abuse potential studies of ALO-02. The opinion will cover whether opioids should be used for CLBP, when they should be used and opioid choices.
EXPERT OPINION
ALO-02 is one of several opioids which can be considered in the management of CLBP. The outcome to a trial of opioids should be function rather than analgesia. Most analgesic trials for CLBP have had analgesia as the primary outcome and function has not been vigorously studied as an outcome. Opioids should be considered as a trial only when other non-opioid analgesics have failed to improve analgesia and function. Universal precautions should be routinely part of phase III analgesic trial particularly for chronic non-malignant pain.
Topics: Analgesics, Opioid; Animals; Chronic Pain; Delayed-Action Preparations; Drug Combinations; Humans; Low Back Pain; Naltrexone; Opioid-Related Disorders; Oxycodone; Practice Guidelines as Topic
PubMed: 27253690
DOI: 10.1080/17425255.2016.1191469 -
BMJ Supportive & Palliative Care Jun 2018To assess the efficacy, tolerability and acceptability of oxycodone for cancer pain in adults METHODS: We searched CENTRAL, MEDLINE, MEDLINE In-Process, Embase, SCI,... (Review)
Review
OBJECTIVES
To assess the efficacy, tolerability and acceptability of oxycodone for cancer pain in adults METHODS: We searched CENTRAL, MEDLINE, MEDLINE In-Process, Embase, SCI, Conference Proceedings Citation Index-Science, BIOSIS, PsycINFO and four trials registries to November 2016.
RESULTS
We included 23 randomised controlled trials with 2144 patients analysed for efficacy and 2363 for safety. Meta-analyses showed no significant differences between controlled-release (CR) and immediate-release oxycodone in pain intensity or adverse events but did show significantly better pain relief after treatment with CR morphine compared with CR oxycodone. However, sensitivity analysis did not corroborate this result. Meta-analyses of the adverse events showed a significantly lower risk of hallucinations after treatment with CR oxycodone compared with CR morphine, but no other differences. The remaining studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None found any clear superiority or inferiority of oxycodone in pain relief or adverse events. The quality of this evidence base was limited by the high/unclear risk of bias of the studies and the low event rates for many outcomes.
CONCLUSIONS
Oxycodone offers similar levels of pain relief and adverse events to other strong opioids. However, hallucinations occurred less with CR oxycodone than with CR morphine, but the quality of this evidence was very low, so this finding should be treated with utmost caution. Our conclusions are consistent with other reviews and suggest that oxycodone can be used first line as an alternative to morphine. However, because it is cheaper, morphine generally remains the first-line opioid of choice.
Topics: Analgesics, Opioid; Cancer Pain; Humans; Oxycodone; Pain Management; Patient Preference; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29331953
DOI: 10.1136/bmjspcare-2017-001457 -
Chemico-biological Interactions Sep 2022Cancer patients experience pain during medical treatment. Therefore, anticancer drugs and painkillers are often prescribed together. This study aims to determine the...
PURPOSE
Cancer patients experience pain during medical treatment. Therefore, anticancer drugs and painkillers are often prescribed together. This study aims to determine the interaction between anlotinib and oxycodone and reveal the underlying mechanism.
METHODS
UPLC-MS/MS, an efficient and sensitive method, was used for the simultaneous determination of oxycodone and oxycodone metabolites. Sprague-Dawley rats were given oxycodone with or without anlotinib. Then, UPLC-MS/MS was used to determine the blood concentration of oxycodone. To study the interaction mechanism, rat and human liver microsomes (HLMs) were used for determining enzyme kinetics.
RESULTS
Long-term administration of oxycodone combined with anlotinib resulted in significantly increased pharmacokinetic parameters AUC, AUC, and C for oxycodone, indicating that anlotinib inhibited oxycodone. In vitro kinetic measurements indicated that anlotinib inhibited the metabolism of oxycodone through a mixed mechanism. Further studies indicated that in HLMs, anlotinib strongly inhibited the metabolism of oxycodone.
CONCLUSION
This study showed that anlotinib inhibited the metabolism of oxycodone both in vitro and in vivo. It is recommended that the dose of oxycodone should be reconsidered when oxycodone is combined with anlotinib in clinical practice.
Topics: Animals; Chromatography, Liquid; Humans; Indoles; Oxycodone; Quinolines; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry
PubMed: 35853539
DOI: 10.1016/j.cbi.2022.110044 -
Organic Letters Dec 2014Our novel synthetic route to (-)-oxycodone, a semisynthetic opioid analgesic, features a palladium-catalyzed direct intramolecular arylation of an aryl bromide,...
Our novel synthetic route to (-)-oxycodone, a semisynthetic opioid analgesic, features a palladium-catalyzed direct intramolecular arylation of an aryl bromide, oxidative dearomatization of a dihydrophenanthrenol, formation of a benzylic quaternary carbon by an intramolecular Michael addition of a malonate moiety, and construction of the morphinan skeleton via a Hofmann rearrangement/lactamization cascade.
Topics: Analgesics, Opioid; Catalysis; Hydrocarbons, Brominated; Molecular Structure; Oxycodone; Palladium; Stereoisomerism
PubMed: 25423610
DOI: 10.1021/ol503175n -
Pain Medicine (Malden, Mass.) Feb 2016
Topics: Analgesics, Opioid; Chronic Pain; Humans; Oxycodone; Pain Management
PubMed: 26803845
DOI: 10.1093/pm/pnv106 -
Journal of the Chinese Medical... May 2022Opioids are effective for severe pain; however, the safety issue is also a primary concern. To better understand the opioid use in Taiwan, we conducted this study.
BACKGROUND
Opioids are effective for severe pain; however, the safety issue is also a primary concern. To better understand the opioid use in Taiwan, we conducted this study.
METHODS
Data on patients with opioid prescriptions, including morphine, fentanyl, pethidine, codeine, oxycodone, hydromorphone, and buprenorphine were collected using the Taiwan National Health Insurance Database (NHID).
RESULTS
Our analysis of opioid prescriptions from 2008 to 2018 in Taiwan indicated that (1) A slow increase in prevalence of opioid prescription was found during the study period. Among the drugs studied, morphine accounted for the majority of the prescriptions written, with a gradual increase annually. Pethidine prescriptions showed a significant and rapid decline over the years; (2) medical centers prescribed the largest number of opioids, followed by regional hospitals, local hospitals, and clinics; (3) the number of prescriptions per year per capita in cancer group was much higher than that in noncancer group. In noncancer group, most of the prescriptions were used in acute pain service (98.7%); and (4) use of opioids increased with age in both cancer and noncancer patients.
CONCLUSION
The total number of opioid prescriptions in Taiwan gradually increased annually, among which morphine was the most commonly used opioid. Cancer patients consumed more opioid prescriptions than noncancer patients and most of the prescriptions in noncancer patients were used in acute pain service. The number of prescriptions increased with the age of the patients in both cancer and noncancer patients. The low prescription rate of opioids in chronic pain in Taiwan is not similar as those in high opioid-consuming countries, such as United States.
Topics: Analgesics, Opioid; Chronic Pain; Drug Prescriptions; Humans; Meperidine; Morphine; Neoplasms; Oxycodone; Prevalence; Taiwan; United States
PubMed: 35353736
DOI: 10.1097/JCMA.0000000000000720 -
BMJ Supportive & Palliative Care Jan 2024Although there is low-quality evidence, there has been an increase in publications on the experience of evaluating and managing cancer-related breathlessness using... (Review)
Review
INTRODUCTION
Although there is low-quality evidence, there has been an increase in publications on the experience of evaluating and managing cancer-related breathlessness using opioids other than morphine.
METHODS
The author conducted a non-systematic literature review in the PubMed/Medline and Embase until 4 October 2022. Eligible studies have evaluated the efficacy of opioids other than morphine for cancer-related breathlessness. Studies focused on sedation, anaesthesia, paediatric patients, opioid toxicity or basic research were excluded. Reviews/meta-analyses and non-English language publications were also excluded.
RESULTS
A total of 1556 records were identified, of which 23 studies including 469 patients who were treated with fentanyl (n=223), oxycodone (n=171) and hydromorphone (n=75) were considered eligible. Six phase II randomised clinical trials (RCTs), four observational studies and four case reports of fentanyl were found. For breathlessness on exertion, fentanyl yielded promising results, but no RCT showed significant superiority of fentanyl to placebo or morphine. For terminal breathlessness, three RCTs, five non-randomised or observational studies and one case report on oxycodone or hydromorphone were found. Although the results of the observational studies suggested that oxycodone and hydromorphone might be effective alternatives to morphine, the superiority over placebo or non-inferiority to morphine had not been demonstrated in the RCTs.
CONCLUSION
As an alternative to morphine, the author recommends fentanyl for breathless crisis or breathlessness on exertion, and oxycodone or hydromorphone for terminal breathlessness in advanced cancer. Larger and well-designed studies based on firm research policies are needed to confirm this current knowledge.
Topics: Child; Humans; Analgesics, Opioid; Dyspnea; Fentanyl; Hydromorphone; Morphine; Neoplasms; Oxycodone
PubMed: 37468224
DOI: 10.1136/spcare-2022-004115 -
British Journal of Clinical Pharmacology Feb 2017This prospective study aimed to characterize the population pharmacokinetics of intravenous oxycodone and to determine the minimum effective concentration (MEC) and... (Clinical Trial)
Clinical Trial
AIMS
This prospective study aimed to characterize the population pharmacokinetics of intravenous oxycodone and to determine the minimum effective concentration (MEC) and minimum effective analgesic concentration (MEAC) of oxycodone for major open intra-abdominal surgery.
METHODS
In the pharmacokinetic study, patients were administered intravenous oxycodone (0.1 mg kg ), and arterial blood was sampled at pre-set intervals. In the analgesic-potency study, patients were administered intravenous oxycodone (0.1 mg kg ) 30 min before the end of the surgery, were placed in the postoperative anaesthesia care unit (PACU), and were asked to rate their pain every 10 min using a visual analogue scale (0 = no pain, 10 = most severe pain). On the first occasion that wound pain at rest and during compression was rated as ≥3 or ≥5, respectively, the first blood sample was obtained to determine the MEC. A second blood sample was obtained after titration with 2 mg of oxycodone to yield wound pain <3 at rest and <5 during wound compression, and MEAC was determined. MEC and MEAC were determined again in each patient.
RESULTS
In the population pharmacokinetic study (n = 54), oxycodone plasma concentration over time was well described by a three-compartment mammillary model. Lean body mass and age were significant covariates for the volume of distribution and metabolic clearance of the pharmacokinetic model of oxycodone, respectively. The analgesic-potency study (n = 50) showed that the median (95% CI) MEC and MEAC were 31.5 (19.2-42.8) and 74.1 (29.2-128.3) ng ml (first measurements) and 63.4 (15.6-120.1) and 76.1 (32.9-132.7) ng ml (second measurements), respectively.
CONCLUSIONS
In major intra-abdominal open surgery, the MEAC and analgesic potency of oxycodone were 75 ng ml and 60 ng ml , respectively.
Topics: Abdomen; Administration, Intravenous; Aged; Analgesics, Opioid; Female; Humans; Male; Middle Aged; Models, Biological; Oxycodone; Pain Measurement; Pain, Postoperative; Prospective Studies
PubMed: 27558774
DOI: 10.1111/bcp.13101 -
Critical Care Medicine Dec 2023The objective of this study was to compare pain control and opioid consumption in critically ill patients who were treated with buprenorphine sublingual or oxycodone...
OBJECTIVES
The objective of this study was to compare pain control and opioid consumption in critically ill patients who were treated with buprenorphine sublingual or oxycodone oral/enteral during ICU admission.
DESIGN
This was a retrospective, parallel, cohort study.
SETTING
General medical or surgical ICUs of a quaternary, urban hospital in Sydney, NSW, Australia.
PATIENTS
Data were obtained for all patients admitted to two general medical or surgical ICU from January 2019 to January 2023. Patients were grouped as those who received buprenorphine sublingual versus oxycodone oral/enteral.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Pain control was compared between a propensity score matched cohort of patients who received buprenorphine versus oxycodone. The primary outcome was the probability of significant pain. A significant pain score was defined as greater than or equal to 4 on the 0-10 Numeric Rating Scale or greater than or equal to 6 on the Behavioral Pain Scale. The study cohort included 1,070 patients (288 buprenorphine and 782 oxycodone). After propensity score matching, there were 288 patients in each group. The mean age of the matched cohort was 64 ± 16 years, 295 (51%) were male, and 359 (62%) had a surgical admission. The median probability of significant pain was 0.16 with buprenorphine and 0.17 with oxycodone (median difference, 0.01; 95% CI, -0.02 to 0.04; p = 0.50). Median opioid consumption in oral morphine milligram equivalents (MMEs) was 65 with buprenorphine and 70 with oxycodone (median difference, -1 mg; 95% CI, -10 to 10 mg; p = 0.73). Median MME per ICU day was 22 with buprenorphine and 22 with oxycodone (median difference, 1 mg; 95% CI, -2 to 5 mg; p = 0.38).
CONCLUSIONS
Buprenorphine sublingual is as effective as oxycodone oral/enteral with regard to pain control and opioid consumption in the ICU. Buprenorphine sublingual is an appropriate option for patients in the ICU who are unable to take oral/enteral medications.
Topics: Humans; Male; Middle Aged; Aged; Aged, 80 and over; Female; Buprenorphine; Analgesics, Opioid; Oxycodone; Retrospective Studies; Cohort Studies; Pain
PubMed: 37642505
DOI: 10.1097/CCM.0000000000006031 -
The Medical Letter on Drugs and... Sep 2018
Review
Topics: Abuse-Deterrent Formulations; Analgesics, Opioid; Animals; Cross-Over Studies; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Oxycodone
PubMed: 30383730
DOI: No ID Found