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Drug and Alcohol Dependence Dec 2023Despite the thousands of lives lost during the ongoing opioid crisis, a scarcity of new and effective clinical treatments for opioid use disorder (OUD) remains. To...
Despite the thousands of lives lost during the ongoing opioid crisis, a scarcity of new and effective clinical treatments for opioid use disorder (OUD) remains. To address this unmet need, some researchers have turned to dissociative and psychedelic drugs to treat multiple psychiatric conditions. In particular, low doses of ketamine have been shown to attenuate opioid withdrawal and drug use in clinical and preclinical studies. However, ketamine has misuse liability and dissociative side effects that may limit its widespread application as a treatment for OUD. More recently, (2R,6R)-hydroxynorketamine (HNK), a ketamine metabolite that lacks misuse potential, has gained attention for its effectiveness in depression and stress models. To uncover its role in OUD, we tested the time-dependent effects of (2R,6R)-HNK on oxycodone withdrawal and reinstatement of oxycodone conditioned place preference (CPP). In male and female oxycodone-dependent mice, we found that 24h pretreatment with (2R,6R)-HNK (10 or 30mg/kg, s.c.) reduced the frequency of withdrawal-like behaviors and global withdrawal scores during naloxone-precipitated withdrawal, whereas 1h pretreatment with (2R,6R)-HNK only reduced paw tremors and the sum of global withdrawal scores but not GWS Z-scores. In other experiments, both 1h and 24h pretreatment with (2R,6R)-HNK (30mg/kg, s.c.) blocked drug-induced reinstatement of oxycodone CPP. Finally, we found (2R,6R)-HNK (30mg/kg, sc) had no effect on locomotor activity and thigmotaxis. Together, these results indicate that acute (2R,6R)-HNK has efficacy in some preclinical models of OUD without producing locomotor or anxiety-like side effects.
Topics: Humans; Mice; Male; Female; Animals; Ketamine; Antidepressive Agents; Oxycodone; Hallucinogens
PubMed: 37864957
DOI: 10.1016/j.drugalcdep.2023.110987 -
British Journal of Clinical Pharmacology Jul 2024Oxycodone is the most commonly prescribed strong opioid in Australia. This study describes health service antecedents and sociodemographic factors associated with...
AIMS
Oxycodone is the most commonly prescribed strong opioid in Australia. This study describes health service antecedents and sociodemographic factors associated with oxycodone initiation.
METHODS
Population-based new user cohort study linking medicine dispensings, hospitalizations, emergency department visits, medical services and cancer notifications from New South Wales (NSW) for 2014-2018. New users had no dispensings of any opioid in the preceding year. We analysed health service use in the 5 days preceding initiation and proportion of people on treatment over 1 year and fitted an area-based, multivariable initiation model with sociodemographic covariates.
RESULTS
Oxycodone accounted for 30% of opioid initiations. Annually, 3% of the NSW population initiated oxycodone, and 5-6% were prevalent users; the new user cohort comprised 830 963 people. Discharge from hospital (39.3%), therapeutic procedures (21.4%) and emergency department visits (19.7%) were common; a hospital admission for injury (6.0%) or a past-year history of cancer (7.2%) were less common. At 1 year after initiation, 4.6% of people were using oxycodone. In the multivariable model, new use of oxycodone increased with age and was higher for people outside major cities, for example, an incidence rate ratio of 1.43 (95% confidence interval 1.36-1.51) for inner regional areas relative to major cities; there was no evidence of variation in rates of new use by social disadvantage.
CONCLUSION
About half of new oxycodone use in NSW was preceded by a recent episode of hospital care or a therapeutic procedure. Higher rates of oxycodone initiation in rural and regional areas were not explained by sociodemographic factors.
Topics: Humans; Oxycodone; Male; Female; Middle Aged; Adult; Analgesics, Opioid; New South Wales; Aged; Adolescent; Young Adult; Hospitalization; Emergency Service, Hospital; Sociodemographic Factors; Cohort Studies; Child; Aged, 80 and over; Child, Preschool; Infant
PubMed: 38571341
DOI: 10.1111/bcp.16063 -
Journal of Personalized Medicine May 2024Severe cancer pain substantially affects patients' quality of life, increasing the burden of the disease and reducing the disability-adjusted life years. Although opioid... (Review)
Review
Severe cancer pain substantially affects patients' quality of life, increasing the burden of the disease and reducing the disability-adjusted life years. Although opioid analgesics are effective, they may induce opioid-induced bowel dysfunction (OIBD). Oxycodone/naloxone combination therapy has emerged as a promising approach to mitigate opioid-induced constipation (OIC) while providing effective pain relief. This review provides an updated analysis of the literature of the last decade regarding the use of oxycodone/naloxone in the management of severe cancer pain. Through a comprehensive search of databases, studies focusing on the efficacy, safety, and patient experience of oxycodone/naloxone's prolonged release in severe cancer pain management were identified. Furthermore, the literature discusses the mechanism of action of naloxone in mitigating OIC without compromising opioid analgesia. Overall, the evidence suggests that oxycodone/naloxone combination therapy offers a valuable option for effectively managing severe cancer pain while minimizing opioid-induced constipation, thereby improving patients' quality of life. However, further research is needed to optimize dosing regimens, evaluate long-term safety, and assess patient outcomes in diverse cancer populations.
PubMed: 38793067
DOI: 10.3390/jpm14050483 -
Clinical Pharmacokinetics Jul 2023Up to 90% of patients with castration-resistant prostate cancer (CRPC) will develop symptomatic bone metastases requiring pain medication, with opioids being the...
BACKGROUND AND OBJECTIVE
Up to 90% of patients with castration-resistant prostate cancer (CRPC) will develop symptomatic bone metastases requiring pain medication, with opioids being the mainstay of therapy in treating moderate and severe pain. Enzalutamide is an androgen receptor antagonist for the treatment of CRPC and a strong inducer of cytochrome P450 (CYP)3A4. Hereby, enzalutamide potentially reduces the exposure of oxycodone, an opioid metabolized by CYP3A4 and CYP2D6. Our objective was to evaluate the potential drug-drug interaction of enzalutamide and oxycodone.
METHODS
A prospective, nonrandomized, open-label, two-arm parallel study was performed. All patients received a single dose of 15 mg normal-release oxycodone. Patients in the enzalutamide arm (ENZ-arm) received enzalutamide 160 mg once daily. Plasma concentrations of oxycodone and its metabolites were quantified using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method.
RESULTS
Twenty-six patients (13 ENZ-arm; 13 control arm) were enrolled in the study. Enzalutamide decreased the mean AUC and C of oxycodone with, respectively, 44.7% (p < 0.001) and 35.5% (p = 0.004) compared with the control arm. The AUC and C of the active metabolite oxymorphone were 74.2% (p < 0.001) and 56.0% (p = 0.001) lower in the ENZ-arm compared with the control arm. In contrast, AUC and C of the inactive metabolites noroxycodone and noroxymorphone were significantly increased by enzalutamide.
CONCLUSION
Co-administration of enzalutamide significantly reduced exposure to oxycodone and its active metabolite oxymorphone in men with prostate cancer. This should be taken into account when prescribing enzalutamide combined with oxycodone.
Topics: Male; Humans; Oxycodone; Oxymorphone; Chromatography, Liquid; Prospective Studies; Prostatic Neoplasms, Castration-Resistant; Tandem Mass Spectrometry; Analgesics, Opioid; Pain
PubMed: 37162620
DOI: 10.1007/s40262-023-01255-1 -
British Journal of Pain Oct 2023The prescription of opioids in emergency care has been associated with harm, including overdose and dependence. The aim of this trial was to assess restriction of access...
BACKGROUND
The prescription of opioids in emergency care has been associated with harm, including overdose and dependence. The aim of this trial was to assess restriction of access to oxycodone (ROXY), in combination with education and guideline modifications, versus education and guideline modifications alone (standard care) to reduce oxycodone administration in the Emergency Department (ED).
METHODS
An unblinded, active control, randomised controlled trial was conducted in an adult tertiary ED. Participants were patients aged 18-75 years who had analgesics administered in the ED. The primary intervention was ROXY, through removal of all oxycodone immediate release tablets from the ED imprest, with availability of a small supply after senior clinician approval. The intervention did not restrict prescription of discharge medications. The primary outcome measure was oxycodone administration rates. Secondary outcomes were administration rates of other analgesic medications, time to initial analgesics and oxycodone prescription on discharge.
RESULTS
There were 2258 patients eligible for analysis. Oxycodone was administered to 80 (6.1%) patients in the ROXY group and 221 (23.3%) patients in the standard care group (relative risk (RR) 0.26; 95% CI: 0.21 to 0.33; < .001). Tapentadol was prescribed more frequently in the ROXY group (RR 2.17; 95% CI: 1.71-2.74), while there were no differences in prescription of other analgesic medications. On discharge, significantly fewer patients were prescribed oxycodone (RR 0.51; 95% CI: 0.39-0.66) and no differences were observed in prescription rates of other analgesic medications. There was no difference in time to first analgesic (HR 0.94; 95% CI: 0.86-1.02).
CONCLUSIONS
Restricted access to oxycodone was superior to education and guideline modifications alone for reducing oxycodone use in the ED and reducing discharge prescriptions of oxycodone from the ED. The addition of simple restrictive interventions is recommended to enable rapid changes to clinician behaviour to reduce the potential harm associated with the prescribing of oxycodone in the ED.
PubMed: 38107754
DOI: 10.1177/20494637231189031 -
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 -
CMAJ : Canadian Medical Association... Jul 2023Oxycodone is increasingly prescribed for postpartum analgesia in lieu of codeine owing to concerns regarding the neonatal safety of codeine during lactation. We examined...
BACKGROUND
Oxycodone is increasingly prescribed for postpartum analgesia in lieu of codeine owing to concerns regarding the neonatal safety of codeine during lactation. We examined whether initiation of oxycodone after delivery was associated with an increased risk of persistent opioid use relative to initiation of codeine.
METHODS
We conducted a population-based cohort study of people who filled a prescription for either codeine or oxycodone within 7 days of discharge from hospital after delivery between Sept. 1, 2012, and June 30, 2020. The primary outcome was persistent opioid use, defined as 1 or more additional prescriptions for an opioid within 90 days of the first postpartum prescription and 1 or more additional prescriptions in the 91 to 365 days thereafter. We used inverse probability of treatment weighting to assess the risk of persistent postpartum opioid use, comparing people who initiated oxycodone with those who initiated codeine.
RESULTS
Over the 8-year study period, we identified 70 607 people who filled an opioid prescription within 7 days of discharge from hospital: 21 308 (30.2%) received codeine and 49 299 (69.8%) oxycodone. Compared with people who filled a prescription for codeine, receipt of oxycodone was not associated with persistent opioid use (relative risk [RR] 1.04, 95% confidence interval [CI] 0.91-1.20). We found an association between a prescription for oxycodone and persistent use after vaginal delivery (RR 1.63, 95% CI 1.31-2.03), but not after cesarean delivery (RR 0.85, 95% CI 0.73-1.00).
INTERPRETATION
Initiation of oxycodone (v. codeine) was not associated with an increased risk of persistent opioid use, except after vaginal delivery.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Codeine; Oxycodone; Analgesics, Opioid; Cohort Studies; Retrospective Studies; Opioid-Related Disorders; Drug Prescriptions
PubMed: 37524396
DOI: 10.1503/cmaj.221351 -
Supportive Care in Cancer : Official... Oct 2023Although opioids have been shown to be effective for cancer pain, opioid-induced adverse events (AEs) are common. To date, little is known about the differences in risks...
PURPOSE
Although opioids have been shown to be effective for cancer pain, opioid-induced adverse events (AEs) are common. To date, little is known about the differences in risks of AEs by opioid type. This study was performed to compare the prevalence of AEs across opioids commonly used for analgesic treatment in Japan.
METHODS
This study was conducted as a preplanned secondary analysis of a multicenter prospective longitudinal study of inpatients with cancer pain who received specialized palliative care for cancer pain relief. We assessed daily AEs until termination of follow-up. We rated the severity of AEs based on the Common Terminology Criteria for Adverse Events version 5.0. We computed adjusted odds ratios for each AE (constipation, nausea and vomiting, delirium, and drowsiness) with the following variables: opioid, age, sex, renal dysfunction, and primary cancer site.
RESULTS
In total, 465 patients were analyzed. Based on the descriptive analysis, the top four most commonly used opioids were included in the analysis: oxycodone, hydromorphone, fentanyl, and tramadol. With respect to the prevalence of AEs among all analyzed patients, delirium (n = 25, 6.3%) was the most frequent, followed by drowsiness (n = 21, 5.3%), nausea and vomiting (n = 19, 4.8%), and constipation (n = 28, 4.6%). The multivariate logistic analysis showed that no single opioid was identified as a statistically significant independent predictor of any AE.
CONCLUSION
There was no significant difference in the prevalence of AEs among oxycodone, fentanyl, hydromorphone, and tramadol, which are commonly used for analgesic treatment in Japan.
Topics: Humans; Analgesics, Opioid; Oxycodone; Hydromorphone; Cancer Pain; Tramadol; Prospective Studies; Japan; Prevalence; Longitudinal Studies; Fentanyl; Constipation; Nausea; Vomiting; Delirium
PubMed: 37843639
DOI: 10.1007/s00520-023-08099-2 -
Nature Communications Dec 2023The opioid crisis in the United States is primarily driven by the highly potent synthetic opioid fentanyl leading to >70,000 overdose deaths annually; thus, new...
The opioid crisis in the United States is primarily driven by the highly potent synthetic opioid fentanyl leading to >70,000 overdose deaths annually; thus, new therapies for fentanyl overdose are urgently needed. Here, we present the first clinic-ready, fully human monoclonal antibody CSX-1004 with picomolar affinity for fentanyl and related analogs. In mice CSX-1004 reverses fentanyl antinociception and the intractable respiratory depression caused by the ultrapotent opioid carfentanil. Moreover, toxicokinetic evaluation in a repeat-dose rat study and human tissue cross-reactivity study reveals a favorable pharmacokinetic profile of CSX-1004 with no safety-related issues. Using a highly translational non-human primate (NHP) model of respiratory depression, we demonstrate CSX-1004-mediated protection from repeated fentanyl challenges for 3-4 weeks. Furthermore, treatment with CSX-1004 produces up to a 15-fold potency reduction of fentanyl in NHP respiration, antinociception and operant responding assays without affecting non-fentanyl opioids like oxycodone. Taken together, our data establish the feasibility of CSX-1004 as a promising candidate medication for preventing and reversing fentanyl-induced overdose.
Topics: Humans; Rats; Mice; Animals; United States; Analgesics, Opioid; Antibodies, Monoclonal; Fentanyl; Drug Overdose; Respiratory Insufficiency
PubMed: 38052779
DOI: 10.1038/s41467-023-43126-0 -
BMJ Open Oct 2023Postoperative pain is a main component influencing the recovery of patients with lung cancer. The combination of patient-controlled intravenous analgesia (PCIA) and...
Effect of oxycodone combined with ultrasound-guided thoracic paravertebral nerve block on postoperative analgesia in patients with lung cancer undergoing thoracoscopic surgery: protocol for a randomised controlled study.
INTRODUCTION
Postoperative pain is a main component influencing the recovery of patients with lung cancer. The combination of patient-controlled intravenous analgesia (PCIA) and paravertebral nerve block for postoperative analgesia in patients undergoing thoracoscopic lobectomy for lung cancer can achieve a satisfactory analgesic effect and promote early rehabilitation of patients. The objective is to investigate the optimal dose of oxycodone for PCIA combined with paravertebral nerve block, to achieve effective multimodal analgesia management in patients undergoing thoracoscopic lung cancer lobectomy.
METHODS AND ANALYSIS
This prospective, double-blind, single-centre, parallel-group, superiority study from 7 April 2023 to 31 December 2024 will include 160 participants scheduled for thoracoscopic lobectomy for lung cancer. Participants will be randomly assigned to four groups in a 1:1:1:1 ratio: OCA group (oxycodone: 0.5 mg/kg), OCB group (oxycodone: 1.0 mg/kg), OCC group (oxycodone: 1.5 mg/kg) and one sufentanil group (sufentanil: 2 µg/kg). Flurbiprofen 50 mg and ondansetron 16 mg are added to each group. All the drugs are diluted with 0.9% saline in a 100 mL volume, with a background infusion rate of 2 mL/hour, a bolus dose of 0.5 mL and a lockout interval of 15 min. The primary outcome is pain scores at rest and dynamic at 24 hours after surgery using a Numeric Rating Scale (NRS). Dynamic NRS scores are defined as NRS when coughing. NRS scores will be assessed at 2, 4, 12, 24 and 48 hours postoperatively. The secondary outcomes include the following variables: (1) NRS score at rest and dynamic at 2, 4, 12 and 48 hours postoperatively; (2) total dose of sufentanil or oxycodone consumption in PCIA; (3) the times of patient-controlled analgesia; (4) Ramsay Sedation Score (RSS) at 2, 4, 12, 24 and 48 hours after the surgery; (5) extubation time; (6) serum C-reactive protein and interleukin six levels; (7) incidence of postoperative nausea and vomiting; (8) incidence of itching; (9) incidence of respiratory depression and (10) gastrointestinal recovery (exhaust time).
ETHICS AND DISSEMINATION
The First Affiliated Hospital of Shandong First Medical University's Ethics Committee granted consent for this study (approval number: YXLL-KY-2022(116)). To enable widespread use of the data gathered, we plan to publish the trial's findings in an appropriate scientific journal after it is complete.
TRIAL REGISTRATION NUMBER
NCT05742256.
Topics: Humans; Oxycodone; Sufentanil; Prospective Studies; Thoracoscopy; Pain, Postoperative; Analgesia, Patient-Controlled; Nerve Block; Lung Neoplasms; Ultrasonography, Interventional; Analgesics, Opioid; Randomized Controlled Trials as Topic
PubMed: 37844986
DOI: 10.1136/bmjopen-2023-074416