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Journal of Opioid Management 2020Opioids can be an effective treatment option for appropriate patients with chronic pain for whom nonpharmacological or nonopioid treatment does not provide adequate pain... (Review)
Review
Opioids can be an effective treatment option for appropriate patients with chronic pain for whom nonpharmacological or nonopioid treatment does not provide adequate pain relief. However, extended-release (ER) opioid formulations, because of their high drug content, are attractive options for nonmedical use and abuse. Xtampza ER (oxycodone DETERx) capsules, an ER abuse-deterrent formulation (ADF), contain microspheres that combine oxycodone with inactive ingredients to increase the difficulty of tampering with the ER mechanism. The aim of this article is to review five previously published studies highlighting the impact of physical manipula-tion (ie, crushing and chewing) on the pharmacokinetic (PK) properties of orally administered Xtampza ER compared with immedi-ate-release (IR) oxycodone and/or reformulated OxyContin (the first approved oxycodone ER ADF). Across five studies, manipulated (crushed or chewed) Xtampza ER retained an ER PK profile similar to that of intact Xtampza ER, with respect to maximum plasma con-centration (Cmax) and time to Cmax. Additionally, bioequivalence was established between manipulated and intact Xtampza ER, based on Cmax and area under the concentration-time curve values in healthy volunteers and nondependent recreational opioid users. In contrast, crushed OxyContin failed to retain the ER PK profile of intact OxyContin and was bioequivalent to IR oxycodone, based on Cmax in healthy volunteers. The retention of ER PK properties when capsule contents are physically manipulated before oral administra-tion suggests Xtampza ER has lower potential to be manipulated for oral abuse when compared with IR oxycodone or OxyContin.
Topics: Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Humans; Opioid-Related Disorders; Oxycodone
PubMed: 32329888
DOI: 10.5055/jom.2020.0559 -
Acta Anaesthesiologica Scandinavica May 2020Parenteral opioids are used for pain relief in labour but there are little data for oxycodone in this context. The aim of this study was to evaluate the efficacy, foetal...
BACKGROUND
Parenteral opioids are used for pain relief in labour but there are little data for oxycodone in this context. The aim of this study was to evaluate the efficacy, foetal exposure and safety of subcutaneous oxycodone in the latent phase of labour.
METHODS
This pragmatic trial included 76 parturients, who received subcutaneous oxycodone for pain relief in the latent phase of labour according to the hospital protocol: an initial dose 0.1 mg/kg, and a second dose, 0.05 mg/kg, could be administered four hours later. Pain intensity and pain relief were assessed using a numerical rating scale of 0-10. After delivery, blood samples from the maternal and umbilical veins were collected, and plasma concentrations of oxycodone and its main metabolites were quantified using UPLC-MS/MS. The Apgar scores and maternal and neonatal adverse effects were recorded.
RESULTS
The foetal exposure at birth was low, the median oxycodone and oxymorphone umbilical vein plasma concentrations were 1.2 ng/mL (range 0.21-7.8) and 0.14 ng/mL (0-0.26), respectively. Pain scores decreased substantially, from a median pain score of 7/10 before oxycodone to median scores of 5/10 at 30 minutes after administration, 5/10 at 60 minutes and 6/10 at 120 minutes. The median Apgar score was 9 (range 2-10) at 1 minute and 9 (6-10) at 5 minutes. Maternal adverse effects were mild, and there were no oxycodone-related neonatal adverse effects.
CONCLUSION
Subcutaneous oxycodone provided effective analgesia during the latent phase of labour. Newborn exposure at birth was low, and oxycodone was well-tolerated.
Topics: Adult; Analgesia, Obstetrical; Analgesics, Opioid; Female; Finland; Humans; Labor Pain; Labor, Obstetric; Oxycodone; Pain Management; Pregnancy; Young Adult
PubMed: 31950485
DOI: 10.1111/aas.13550 -
Scientific Reports May 2023Opioids have been used to manage pain for thousands of years, but they have significant potential for abuse. Prescription opioids, like oxycodone, are associated with...
Opioids have been used to manage pain for thousands of years, but they have significant potential for abuse. Prescription opioids, like oxycodone, are associated with 32% of overdoses, that have reached a total of 75,673 deaths in 2021. A major challenge is maximizing their therapeutic potential while minimizing the negative side effects including opioid use disorder (OUD). The Ketogenic Diet (KD) has been reported to reduce pain and decrease the severity of alcohol use disorder, yet its effects on oxycodone responses remain unknown. KD mice displayed increased oxycodone-induced locomotor activity and enhanced antinociceptive effects of oxycodone, suggesting a dietary effect on opiate sensitivity. Male KD mice exposed to chronic oxycodone exhibited increased naloxone-induced jumps, suggesting a sex-specific effect of diet on opioid withdrawal. Consistent with this, male KD mice self-administered less oxycodone while female KD mice did not differ from controls. Finally, no effect of KD on motivation to obtain oxycodone was observed during a progressive ratio schedule. These data suggest sex-biased effects of KD on responses to opioids that should be considered and potentially leveraged in both clinical pain management and treatment of OUD.
Topics: Female; Male; Animals; Mice; Oxycodone; Diet, Ketogenic; Analgesics, Opioid; Opioid-Related Disorders; Alcoholism; Pain; Psychomotor Agitation
PubMed: 37160959
DOI: 10.1038/s41598-023-33458-8 -
International Journal of Environmental... Oct 2022Chronic low back pain (CLBP) due to osteoarthritis represents a therapeutic challenge worldwide. Opioids are extensively used to treat such pain, but the development of...
Chronic low back pain (CLBP) due to osteoarthritis represents a therapeutic challenge worldwide. Opioids are extensively used to treat such pain, but the development of tolerance, i.e., less susceptibility to the effects of the opioid, which can result in a need for higher doses to achieve the same analgesic effect, may limit their use. Animal models suggest that ultra-low doses of opioid antagonists combined with opioid agonists can decrease or block the development of opioid tolerance. In this retrospective study, we tested this hypothesis in humans. In 2019, 53 patients suffering from CLBP were treated with either Oxycodone and Naloxone Prolonged Release (27 patients, OXN patients) or Oxycodone Controlled Release (26 patients, OXY patients). The follow-up period lasted 2 years, during which 10 patients discontinued the treatment, 5 out of each group. The remaining 43 patients reached and maintained the targeted pain relief, but at 18 and 24 months, the OXY patients showed a significantly higher oxycodone consumption than OXN patients to reach the same level of pain relief. No cases of respiratory depression or opioid abuse were reported. There were no significant differences in the incidence of adverse effects between the two treatments, except for constipation, more common in OXY patients. From our results, we can affirm that a long-term opioid treatment with oxycodone-naloxone combination, when compared with oxycodone only, may significantly hinder the development of opioid tolerance. We were also able to confirm, in our cohort, the well known positive effect of naloxone in terms of opioid-induced bowel dysfunction incidence reduction.
Topics: Humans; Oxycodone; Analgesics, Opioid; Retrospective Studies; Narcotic Antagonists; Low Back Pain; Delayed-Action Preparations; Follow-Up Studies; Drug Tolerance; Naloxone; Drug Combinations; Chronic Pain
PubMed: 36293936
DOI: 10.3390/ijerph192013354 -
PloS One 2020To evaluate the efficacy, safety and cost-effectiveness of Oxycodone Hydrochloride Controlled-release Tablets (CR oxycodone) and Morphine Sulfate Sustained-release... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To evaluate the efficacy, safety and cost-effectiveness of Oxycodone Hydrochloride Controlled-release Tablets (CR oxycodone) and Morphine Sulfate Sustained-release Tablets (SR morphine) for moderate to severe cancer pain titration.
METHODS
Randomized controlled trials meeting the inclusion criteria were searched through Medline, Cochrane Library, Pubmed, EMbase, CNKI,VIP and WanFang database from the data of their establishment to June 2019. The efficacy and safety data were extracted from the included literature. The pain control rate was calculated to eatimate efficacy. Meta-analysis was conducted by Revman5.1.4. A decision tree model was built to simulate cancer pain titration process. The initial dose of CR oxycodone and SR morphine group were 20mg and 30mg respectively. Oral immediate-release morphine was administered to treat break-out pain. The incremental cost-effectiveness ratio was performed with TreeAge Pro 2019.
RESULTS
19 studies (1680 patients)were included in this study. Meta-analysis showed that the pain control rate of CR oxycodone and SR morphine were 86% and 82.98% respectively. The costs of CR oxycodone and SR morphine were $23.27 and $13.31. The incremental cost-effectiveness ratio per unit was approximate $329.76. At the willingness-to-pay threshold of $8836, CR oxycodone was cost-effective, while the corresponding probability of being cost-effective at the willingness-to-pay threshold of $300 was 31.6%. One-way sensitivity analysis confirmed robustness of results.
CONCLUSIONS
CR oxycodone could be a cost-effective option compared with SR morphine for moderate to severe cancer pain titration in China, according to the threshold defined by the WHO.
Topics: Cancer Pain; Cost-Benefit Analysis; Decision Trees; Delayed-Action Preparations; Economics, Pharmaceutical; Humans; Morphine; Oxycodone; Publication Bias; Risk; Treatment Outcome
PubMed: 32302346
DOI: 10.1371/journal.pone.0231763 -
Chemistry (Weinheim An Der Bergstrasse,... Mar 2020N-Demethylation of oxycodone is one of the key steps in the synthesis of important opioid antagonists like naloxone or analgesics like nalbuphine. The reaction is...
N-Demethylation of oxycodone is one of the key steps in the synthesis of important opioid antagonists like naloxone or analgesics like nalbuphine. The reaction is typically carried out using stoichiometric amounts of toxic and corrosive reagents. Herein, we present a green and scalable organophotocatalytic procedure that accomplishes the N-demethylation step using molecular oxygen as the terminal oxidant and an organic dye (rose bengal) as an effective photocatalyst. Optimization of the reaction conditions under continuous flow conditions using visible-light irradiation led to an efficient, reliable, and scalable process, producing noroxycodone hydrochloride in high isolated yield and purity after a simple workup.
Topics: Analgesics; Demethylation; Humans; Morphinans; Oxycodone
PubMed: 31898822
DOI: 10.1002/chem.201905505 -
Biopharmaceutics & Drug Disposition Feb 2020Oxycodone is an opioid analgesic with several pharmacologically active metabolites and relatively narrow therapeutic index. Cytochrome P450 (CYP) 3A4 and CYP2D6 play...
Oxycodone is an opioid analgesic with several pharmacologically active metabolites and relatively narrow therapeutic index. Cytochrome P450 (CYP) 3A4 and CYP2D6 play major roles in the metabolism of oxycodone and its metabolites. Thus, inhibition and induction of these enzymes may result in substantial changes in the exposure of both oxycodone and its metabolites. In this study, a physiologically based pharmacokinetic (PBPK) model was built using GastroPlus™ software for oxycodone, two primary metabolites (noroxycodone, oxymorphone) and one secondary metabolite (noroxymorphone). The model was built based on literature and in house in vitro and in silico data. The model was refined and verified against literature clinical data after oxycodone administration in the absence of drug-drug interactions (DDI). The model was further challenged with simulations of oxycodone DDI with CYP3A4 inhibitors ketoconazole and itraconazole, CYP3A4 inducer rifampicin and CYP2D6 inhibitor quinidine. The magnitude of DDI (AUC ratio) was predicted within 1.5-fold error for oxycodone, within 1.8-fold and 1.3-4.5-fold error for the primary metabolites noroxycodone and oxymorphone, respectively, and within 1.4-4.5-fold error for the secondary metabolite noroxymorphone, when compared to the mean observed AUC ratios. This work demonstrated the capability of PBPK model to simulate DDI of the administered compounds and the formed metabolites of both DDI victim and perpetrator. However, the predictions for the formed metabolites tend to be associated with higher uncertainty than the predictions for the administered compound. The oxycodone model provides a tool for forecasting oxycodone DDI with other CYP3A4 and CYP2D6 DDI perpetrators that may be co-administered with oxycodone.
Topics: Computer Simulation; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; Gene Expression Regulation, Enzymologic; Humans; Models, Biological; Oxycodone; Software
PubMed: 31925778
DOI: 10.1002/bdd.2215 -
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 -
The Medical Letter on Drugs and... Sep 2001
Topics: Administration, Oral; Delayed-Action Preparations; Humans; Morphine Dependence; Neoplasms; Opioid-Related Disorders; Oxycodone; Pain; Parenteral Nutrition, Total
PubMed: 11581580
DOI: No ID Found -
Clinical Therapeutics Nov 2005The use of the opioid oxycodone hydrochloride in the management of chronic pain is gaining popularity principally because of its tolerability. However, opioid-related...
BACKGROUND
The use of the opioid oxycodone hydrochloride in the management of chronic pain is gaining popularity principally because of its tolerability. However, opioid-related seizure in patients with epilepsy or other conditions that may decrease seizure threshold has been described in the literature; in particular, oxycodone has been associated with seizure in a patient with acute renal failure.
OBJECTIVE
The aim of this article was to report a patient with a history of seizures but normal renal and hepatic function who developed seizure on 2 occasions after oxycodone ingestion.
METHODS
A 54-year-old male patient presented with a history of tonic-clonic seizures that developed immediately after intracranial surgery. Long-term treatment with carbamazepine 400 mg QD was started, and the patient was free of convulsions for approximately 7 years. The patient presented to us with severe headache that was nonresponsive to an NSAID and the opiate agonist tramadol. Treatment with controlled-release (CR) oxycodone and tramadol drops (50 mg QID if necessary) was started, and tonic-clonic seizures developed 3 days later.
RESULTS
Based on laboratory analysis, the patient had normal renal and hepatic function. On discontinuation of oxycodone treatment, the seizures resolved. However, due to effective pain relief with oxycodone, the patient decided to continue treatment, and seizures recurred. Carbamazepine was then administered 4 hours before oxycodone dosing, which allowed continuation of treatment without seizure.
CONCLUSIONS
A patient with a history of seizures controlled with long-term carbamazepine therapy developed seizures when he started treatment with oxycodone CR at recommended doses. Oxycodone CR should be used with extreme caution in patients with epilepsy or other conditions that may decrease seizure threshold.
Topics: Analgesics, Opioid; Delayed-Action Preparations; Headache; Humans; Male; Middle Aged; Oxycodone; Seizures
PubMed: 16368452
DOI: 10.1016/j.clinthera.2005.11.001