Trends in oxycodone and oxycodone-containing analgesics administration for back pain in emergency departments in the USA(2007–2018)

BACKGROUND:To describe trends in oxycodone and oxycodone-containing analgesic prescribing for the treatment of back pain among adults in emergency departments(EDs) in the USA from 2007 to 2018.METHODS:Data were gathered from the National Hospital Ambulatory Medical Care Survey(NHAMCS) from 2007 to 2018.The study population included individuals of all ages presenting to USA EDs.The NHAMCS reasons for visit and oxycodone drug ID codes were used to isolate patients with back pain.The main outcome was the proportion of oxycodone and oxycodone-containing analgesics prescribed for back pain in the EDs over the specified time period.RESULTS:There was a relative decrease in the overall administration of oxycodone for back pain in the EDs by 62.3% from 2007(244,000 visits) to 2018(92,000 visits).The proportion of ED patients prescribed with oxycodone-containing analgesics for back pain increased among patients aged 45 years and older(from 43.8% to 57.6%),female patients(from 54.5% to 62.0%),black patients(from 22.5% to 30.4%),and Hispanic/Latino patients(from 9.4% to 19.6%).Oxycodone/acetaminophen was most prescribed and accounted for 90.2% of all oxycodone-containing analgesics in 2007,with a decrease to 68.5% in 2018.Pure oxycodone was the second most prescribed medication,accounting for 6.1% in 2007 and 31.5% in 2018.CONCLUSION:The overall number of oxycodone-containing analgesics decreased significantly from 2007 to 2018.However,that number trended upward in 45-year-old and older,female,black,or Hispanic/Latino patients from 2007 to 2018.The total amount of pure oxycodone increased significantly from 2007 to 2008.

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

Background: Controlled-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.Methods: In 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 OXNCR or OX-CR groups. OXN-CR was administered starting at 20 mg/10 mg per day and up-titrated to a maximum of80 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 week4, with non-inferiority margin of-1.5. Secondary endpoints included analgesic rescue medication intake, patientreported change in bowel habits, laxative intake, quality of life(QoL), and safety assessments.Results: Of 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.Conclusions: OXN-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。

Advances in the clinical application of oxycodone in the perioperative period

To review the research progress of pure opioid receptor agonist oxycodone.The research progress of oxycodone in terms of pharmacokinetics,pharmacodynamics,adverse reactions,clinical application,combined medication and new progress in clinical application was summarized by referring to the literature.Oxycodone is a semi-synthetic thebaine derivative of opioid alkaloids,and is a pure opioidμandκreceptor agonist.The main action sites are the central nervous system and visceral smooth muscle.Due to its advantages of low adverse reactions,good analgesic effects,and a wide range of safe doses,the drug has been widely used in the control of acute and chronic postoperative pain,as well as malignant and non-malignant pain.Since the end of the 20^(th) century,researchers have begun to formulate antipyretic analgesics,opioid receptor agonists,opioid receptor antagonists,dopamine receptor antagonists and other drugs with oxycodone in different proportions to enhance the analgesic effect.At the same time,it can reduce the dosage of oxycodone and reduce its adverse reactions,so as to achieve the purpose of limiting opioid abuse.With the continuous research on the efficacy and safety of oxycodone in the perioperative period at home and abroad,oxycodone has become the only dual-opioid potent analgesic that can be used in clinical work.

Simultaneous determination of acetaminophen and oxycodone in human plasma by LC–MS/MS and its application to a pharmacokinetic study

A simple and rapid liquid chromatography-tandem mass spectrometry （LC-MS/MS） method was de- veloped and validated for simultaneous determination of acetaminophen and oxycodone in human plasma. Acetaminophen-d4 and oxycodone-d3 were used as internal standards. The challenge en- countered in the method development that the high plasma concentration level of acetaminophen made the MS response saturated while the desired lower limit of quantification （LLOQ,） for oxycodone was hard to reach was well solved. The analytes were extracted by protein precipitation using acetonitrile. The matrix effect of the analytes was avoided by chromatographic separation using a hydrophilic C18 column coupled with gradient elution. Multiple reaction monitoring in positive ion mode was performed on tandem mass spectrometer employing electrospray ion source. The calibration curves were linear over the concentration ranges of 40.0-8000 ng/mL and 0.200-40.0 ng/mL for acetaminophen and oxycodone, respectively. This method, which could contribute to high throughput analysis and better clinical drug monitoring, was successfully applied to a pharmacokinetic study in healthy Chinese volunteers.

Effect of dexmedetomidine combined with oxycodone on systemic stress response in recovery of gynecological laparoscopic operation

Objective:To study the effect of dexmedetomidine combined with oxycodone on systemic stress response in recovery period of gynecological laparoscopic operation.Methods:A total of 86 patients who received laparoscopic operation in the Second Affiliated Hospital of Kunming Medical University between June 2014 and December 2016 were selected and randomly divided into the dexmedetomidine combined with oxycodone group (DO group) and control group (C group). Before anesthesia induction (T1), at the end of the surgery and before micro pump injection of dexmedetomidine and oxycodone hydrochloride (T2) and in recovery period (T3), serum levels of pituitary-target gland axis-related hormones, vascular activity-related hormones and oxidative stress-related molecules were determined.Results: At T1 and T2, serum TSH, T3, T4, ACTH, Cor, NE, E, ADH, AT-II, ROS, MDA, SOD and HO-1 levels of DO group were not significantly different from those of C group;at T3, serum TSH, T3, T4, ACTH, Cor, NE, E, ADH, AT-II, ROS and MDA levels of DO group were significantly lower than those of C group while SOD and HO-1 levels were significantly higher than those of C group.Conclusions: Dexmedetomidine combined with oxycodone can inhibit the systemic stress response in recovery of gynecological laparoscopic operation.

Development of controlled release bi-layered tablets containing oxycodone hydrochloride

Oxycodone hydrochloride is a semi-synthetic opioid agonist that provides very effective relief for moderate to severe pain in cancer and post-operative patients. Controlled release oxycodone formulations have been studied to enhance the therapeutic effect by providing constant release over the whole dosing interval and improve patient’s convenience by reducing the frequency of administration as well.

Acura制药公司oxycodone口服速释片

羟二氢可待因酮（0xycodone）片剂——OxyADF2期临床试验显示该制剂具有潜在的戒瘾作用。

Comparison of the Efficacy of Oral Oxycodone and Oral Codeine in the Treatment of Post-Craniotomy Pain—A Randomized, Double-Blind Trial

Background: Post-craniotomy pain has been reported to be moderate to severe. Management of post-craniotomy pain is often inadequate, yet limited by the side effects of opioids. We aim to find out the efficacy of oral oxycodone as compared to oral codeine for the treatment of post-craniotomy pain in our institution. Methods: A randomized, double-blinded controlled trial was used to evaluate the efficacy of oral oxycodone versus oral codeine. 40 patients were randomized to the control group of codeine (n = 20) or the experimental group receiving oxycodone (n = 20) in addition to regular oral paracetamol for both groups of patients. Results: There was no difference in the visual analogue scale scores at 24 hours (2.78 versus 1.85, p = 0.11) or side effects in the oxycodone group compared with the codeine group. Conclusions: Oral oxycodone had similar efficacy as oral codeine in the management of post-craniotomy pain.

Effects of oxycodone and fentanyl patient-controlled intravenous analgesia on pain, immune response and stress response after laparoscopic surgery

Objective:To study the effects of oxycodone and fentanyl patient-controlled intravenous analgesia on pain, immune response and stress response after laparoscopic surgery.Methods:Patients undergoing laparoscopic surgery in Xianning Central Hospital between June 2015 and February 2017 were selected and randomly divided into oxycodone group and fentanyl group who received postoperative oxycodone and fentanyl patient-controlled intravenous analgesia respectively. 3 d after surgery and 5 d after surgery, the serum contents of pain-related transmitters, immune indexes, stress-related molecules as well as peripheral blood contents of immune cells were measured.Results: 3 d after surgery and 5 d after surgery, CRP, TNF-α, IL-8, sICAM-1, YKL-40, Cor, C-P, FT3, FT4 and HO-1 contents in serum of oxycodone group were significantly lower than those of fentanyl group whereas CD3+CD4+T cell and CD3+CD8+T cell contents in peripheral blood as well as C3 and C4 contents in serum were significantly higher than those of fentanyl group.Conclusion:oxycodone patient-controlled intravenous analgesia after laparoscopic surgery is better than fentanyl and can reduce the pain degree, inhibit the stress response and improve the immune response.

Comparison of Efficacy and Safety of Oxycodone Versus Fentanyl for Intravenous Patient-Controlled Analgesia in Postoperative Pain Management:A Systematic Review and Meta-Analysis

Backgroud:Intravenous opioid patient-controlled analgesia(IV-PCA)has been suggested as an effective method in postoperative pain management.There are several randomized controlled trials(RCTs)of comparison of oxycodone and fentanyl for IV-PCA in surgical patients.The purpose of this study was to perform a meta-analysis to compare the efficacy and safety of oxycodone and fentanyl for IV-PCA in surgical patients from current data.Methods:The RCTs of oxycodone versus fentanyl for IV-PCA were gathered from PubMed,Embase,Cochrane library,CNKI and VIP data.After data extraction and quality assessment of the included RCTs,the RevMan 5.3 software was applied for meta-analysis of numerical rating scale(NRS)scores,accumulated IV-PCA consumption of oxycodone and fentanyl,patient satisfaction,postoperative nausea and vomiting(PONV),and other adverse events(AEs).Results:Results reported from eight RCTs involving 600 patients are included in the meta-analysis.The NRS score at rest and upon movement of group oxycodone was significantly lower than that of group fentanyl(WMD=-3.85,95%CI-4.93^-2.76,P<0.00001;WMD=-4.31,95%CI-5.79^-2.84,P<0.00001);however,the incidence of PONV and dizziness was obviously increased in group oxycodone than in group fentanyl(OR=2.41,95%CI 1.60~3.63,P<0.0001;OR=3.69,95%CI 2.17~6.26,P<0.00001).Accumulated IV-PCA consumption in group oxycodone was less than in group fentanyl overall the 48 hours postoperatively(WMD=-12.11,95%CI-18.42^-5.80,P=0.0002).There was no significant difference in patient satisfaction between oxycodone and fentanyl(OR=0.73,95%CI 0.11~5.04,P=0.75).Conclusion:According to the evidence,this meta-analysis suggest that oxycodone for IV-PCA is superior to fentanyl in postoperative pain relief,whereas the higher incidence of PONV and dizziness was accompanied with oxycodone.Further large-scale,prospective,observational studies are needed to summarize and analyse the data to draw a fair conclusion.

Clinical observation on treatment of cancer pain with TCM oriented drugs combined with oxycodone sustained-release tablets and nimesulide sustained-release tablets

Objective： To study the effect of the transdermal preparation of traditional Chinese medicine in treating cancer pain. Methods： From October 2016 to January 2018, 126 patients with cancer pain were enrolled and divided into 4 groups, 39 patients in group A （directed TCM permeation）, 26 patients in group B （oxycodone sustained-release tablets）, 32 patients in group C （Chinese medicine directed drug penetration ＋ oxycodone sustained-release tablets）, and 29 patients group D （Chinese medicine directed drug penetration ＋ oxycodone sustained-release tablets ＋ nimesulide sustained release tablets）, according to KPS scores. Results： Transdermal preparations of traditional Chinese medicine can significantly alleviate cancer pain. For the treatment of moderate to severe cancer pain, the Chinese medicine transdermal preparation can reduce the dosage of oxycodone sustained-release tablets. At the same time, the patient＇s KPS and NRS scores were significantly reduced. Moreover, the transdermal preparation of traditional Chinese medicine has a better therapeutic effect on visceral pain. Conclusion： The traditional Chinese medicine tra_nsdermal preparation combined with western medicine for the treatment of cancer pain may be a new method for the treatment of cancer pain.

Effect of oxycodone hydrochloride injection preemptive analgesia on serum inflammatory factors, neurotransmitter index and immune function in patients with laparoscopic cholecystectomy

Objective:To investigate the effect of oxycodone hydrochloride injection preemptive analgesia on serum inflammatory factors, neurotransmitter index and immune function in patients with laparoscopic cholecystectomy.Methods: According to random data table, 113 patients undergoing laparoscopic cholecystectomy were divided into control group (n=57) and observation group (n=56), patients in the control group were treated with sufentanil citrate injection analgesia, and the observation group patients were given oxycodone hydrochloride injection analgesia, level of serum inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)], neurotransmitter index [5-hydroxy tryptamine (5-HT), P substance] and immune function index [CD4+, CD8+, CD4+/CD8+] of two groups between preoperative and postoperative 1d were compared.Results: There were no significant difference in level of TNF-α, IL-6, 5-HT, P substance, CD4+, CD8+ and CD4+/CD8+ between the two groups preoperative. Compared with the level of the same group preoperative, at postoperative 1 d level of TNF-α, IL-6, 5-HT, P substance, CD8+were significantly increased, moreover level in the observation group were significantly lower compared with the control group, the difference was statistically significant;Postoperative 1 d, level of CD4+, CD4+/CD8+ in the two groups were significantly lower than the preoperative level within the group, and the observation group was significantly higher than the control group.Conclusion: Oxycodone hydrochloride injection preemptive analgesia in laparoscopic cholecystectomy can effectively reduce serum inflammatory factors and neurotransmitter index release, improve immune function, has an important clinical value.

Analgesic effect of oxycodone combined with parecoxib sodium after laparoscopic cholecystectomy and its influence on inflammatory stress response

Objective: To discuss the analgesic effect of oxycodone combined with parecoxib sodium after laparoscopic cholecystectomy and its influence on inflammatory stress response. Methods:A total of 260 patients with chronic cholecystitis who accepted laparoscopic cholecystectomy in this hospital between December 2016 and May 2017 were divided into control group (n=130) and oxycodone group (n=130) by random number table method. Control group received morphine combined with parecoxib sodium analgesia after operation, and oxycodone group received oxycodone combined with parecoxib sodium analgesia after operation. The differences in serum levels of pain mediators, inflammatory mediators and stress hormones were compared between the two groups immediately after operation (T0), 12 h after operation (T1) and 24 h after operation (T3). Results: At T0, there was no statistically significant difference in serum levels of pain mediators, inflammatory mediators and stress hormones between the two groups. At T1 and T2, serum pain mediators PGE2, NPY, SP and NGF levels of oxycodone group were lower than those of control group whereas β-EP levels were higher than those of control group;serum inflammatory mediators CRP, IL-1β, IL-6 and TNF-αlevels were lower than those of control group;serum stress hormones Cor, NE and INS levels were lower than those of control group. Conclusion: Oxycodone combined with parecoxib sodium analgesia after laparoscopic cholecystectomy can effectively relieve the pain perception and inhibit the systemic inflammatory response and stress response.

Comparison of oxycodone and sufentanil in patient-controlled intravenous analgesia for postoperative patients:a meta-analysis of randomized controlled trials

Background:Managing acute postoperative pain is challenging for anesthesiologists,surgeons,and patients,leading to adverse events despite making significant progress.Patient-controlled intravenous analgesia(PCIA)is a recommended solution,where oxycodone has depicted unique advantages in recent years.However,controversy still exists in clinical practice and this study aimed to compare two drugs in PCIA.Methods:We performed a literature search in PubMed,Embase,the Cochrane Central Register of Controlled Trials,Web of Science,Chinese National Knowledge Infrastructure,Wanfang,and VIP databases up to December 2020 to select specific randomized controlled trials(RCTs)comparing the efficacy of oxycodone with sufentanil in PCIA.The analgesic effect was the primary outcome and the secondary outcome included PCIA consumption,the Ramsay sedation scale,patients’satisfaction and side effects.Results:Fifteen RCTs were included in the meta-analysis.Compared with sufentanil,oxycodone showed lower Numerical Rating Scale scores(mean difference[MD]=-0.71,95%confidence interval[CI]:-1.01 to-0.41;P<0.001;I^(2)=93%),demonstrated better relief from visceral pain(MD=-1.22,95%CI:-1.58 to-0.85;P<0.001;I^(2)=90%),promoted a deeper sedative level as confirmed by the Ramsay Score(MD=0.77,95%CI:0.35-1.19;P<0.001;I^(2)=97%),and resulted in fewer side effects(odds ratio[OR]=0.46,95%CI:0.35-0.60;P<0.001;I^(2)=11%).There was no statistical difference in the degree of patients'satisfaction(OR=1.13,95%CI:0.88-1.44;P=0.33;I^(2)=72%)and drug consumption(MD=-5.55,95%CI:-14.18 to 3.08;P=0.21;I^(2)=93%).Conclusion:Oxycodone improves postoperative analgesia and causes fewer adverse effects,and could be recommended for PCIA,especially after abdominal surgeries.Registration:PROSPERO;https://www.crd.york.ac.uk/PROSPERO/;CRD42021229973.

Meta-analysis of the clinical efficacy and safety of oxycodone and morphine in cancer pain treatment

In the present study, the efficacy and safety of oxycodone and morphine in the treatment of cancer pain were compared in a meta-analysis with the goal of providing a reference for drug selection in clinical practice. Electronic literature databases were searched for articles published through February 2015, including PubMed, MEDLINE, the Cochrane library, and Embase; and the China National Knowledge Intemet, VIP Databases and Wanfang Databases for studies published in Chinese. Only randomized controlled trials were selected. The primary outcome measures were efficacy and the incidence of adverse drug reactions （ADRs）. Data were extracted from the studies by two independent reviewers. A total of 15 studies containing 1338 patients were included in the analysis. The studies were divided into two subgroups according to different scoring methods. The pain relief efficacies of oxycodone and morphine were rated by the numerical rating scale （NRS） （risk ratio [RR]： 1.04; 95% confidence interval [CI]： 0.97-1.11）. Others were rated by the visual analog scale （VAS） （RR： 1.03; 95% CI： 0.97-1.10）. Five studies showed that pain intensity scores did not significantly differ between oxycodone and morphine treatments （standard mean difference [SMD] = 0.16, 95% CI： -0.01-0.33, P = 0.06）. Regarding ADRs, the incidence of constipation was lower in the oxycodone group （RR： 0.70; 95% CI： 0.58-0.85）. No statistical difference was observed among other ADRs. The efficacies of oxycodone and morphine were similar in treating cancer pain. However, the incidence of constipation was lower in patients treated with oxycodone.

Cardiovascular Risk of Opioids: A Real-World Study Based on FAERS

Objective:This research utilizes the FAERS for data mining to identify heart-related side effects caused by opioids,ensuring the safe use of these medications.Methods:Data from 79 quarters(Q12004 to Q32023)involving adverse event(AE)reports for opioids like morphine and oxycodone was reviewed.We applied the MedDRA system to categorize events and used statistical tools,ROR and BCPNN,for signal detection.These findings were cross-checked with drug labels and SIDER 4.1 for accuracy.Identified risks were then categorized by severity using DME and IME classifications.Results:Analysis of adverse events(AEs)for the five examined drugs(35359,14367,144441,10592,and 28848)identified 33,6,12,37,and 34 cardiovascular AEs,and 16,5,7,25,and 21 instances of important medical events(IMEs)respectively.Each drug was linked to cases of cardiac and cardiopulmonary arrest.The cardiovascular AEs varied widely in occurrence and severity,with methadone notably presenting diverse and potent risks,including sudden cardiac death as a distinct medical event(DME).A comparison with SIDER 4.1 showed 11 opioid-related cardiovascular AEs in line with our findings.Standardized MedDRA Queries(SMQs)confirmed these results,indicating stronger signals for methadone and tramadol,while morphine,hydromorphone,and oxycodone exhibited fewer and weaker signals.Conclusion:The study revealed numerous heart-related adverse effects(AEs)not listed on drug labels and identified new AE patterns.Recognizing these differences in AE profiles and risks across different opioids is crucial for safer prescription practices to minimize cardiac complications.

Gender Affects the Median Effective Dose and 95% Effective Dose of Oxycodone for Blunting the Hemodynamic Response to Tracheal Intubation in Narcotic-Naive Adult Patients

Background： Intravenous （IV） oxycodone has been used at induction to prevent an intubation reaction. The aims of the current study were to calculate the median effective dose （ED50） and the 95% effective dose （ED95） of an IV bolus ofoxycodone that blunts the hemodynamic response to tracheal intubation with propofol according to gender and to observe the adverse events of induction-dose oxycodone. Methods： Adult patients who required general anesthesia and tracheal intubation were enrolled. Tracheal intubation was performed using unified TD-C-IV video laryngoscopy and an ordinary common endotracheal tube. Dixon＇s up-and-down method was used to obtain ED50, data for women and men separately. The initial dose of oxycodone was 0.2 mg/kg for women and 0.3 mg/kg for men （step size was 0.01 mg/kg）. Next, a dose-response curve from the probit analysis was generated to determine the ED50 and ED95 to blunt the intubation reaction in female and male patients. Adverse events following oxycodone injection were observed for 5 ,in before propofol injection. Results： Sixty-three patients were analyzed, including 29 females and 34 males. According to the probit analysis, the ED50, and ED95 of oxycodone required to blunt the intubation reaction in women were 0.254 mg/kg （95% confidence interval [CI], 0.220-0.328 mg/kg） and 0.357 mg/kg （95% （21, 0.297-2.563 mg/kg）, respectively. In men, the ED50 and ED95 were 0.324 mg/kg （95% CL 0.274-0.381 mg/kg） and 0.454 mg/kg （95% CI, 0.384-2.862 mg/kg）, respectively. Men required 28% more oxycodone than women for induction （P 〈 0.01 ）. The most common adverse events were dizziness （87.3%）, vertigo （66.7%）, sedation （74.6%）, and respiratory depression （66.7%）. Conclusions： Oxycodone can be used for induction to prevent intubation reactions. Gender affected the ED50 and ED95 ofoxycodone for blunting the tracheal intuhation reaction.

Bioinspired Scalable Total Synthesis of Opioids

As one of the largest and most representative families of natural medicines harvested from plants,the mass production of opioids legitimately occupies large,worldwide farmland cultivation of opium poppies,causing severe regulation limitations and supply uncertainty.Due to their complex structures,the chemical synthesis of opioids has been criticized as infeasible for large-scale production in view of lengthy synthetic steps and overall low efficiency.