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Clinical Pharmacokinetics Jun 2019Global oxycodone consumption has increased sharply during the last two decades, and, in 2008, oxycodone consumption surpassed that of morphine. As oxycodone was... (Review)
Review
Global oxycodone consumption has increased sharply during the last two decades, and, in 2008, oxycodone consumption surpassed that of morphine. As oxycodone was synthesized in 1916 and taken to clinical use a year later, it has not undergone the same approval process required by today's standards. Most of the basic oxycodone pharmacokinetic (PK) data are from the 1990s and from academic research; however, a lot of additional data have been published over the last 10 years. In this review, we describe the latest oxycodone data on special populations, including neonates, children, pregnant and lactating women, and the elderly. A lot of important drug interaction data have been published that must also be taken into account when oxycodone is used concomitantly with cytochrome P450 (CYP) 3A inducers and inhibitors and/or CYP2D6 inhibitors. In addition, we gathered data on abuse-deterrent oxycodone formulations, and the PK of alternate administration routes, i.e. transmucosal and epidural, are also described.
Topics: Adult; Analgesics, Opioid; Biological Availability; Biotransformation; Child; Cytochrome P-450 CYP2D6; Drug Interactions; Female; Half-Life; Humans; Infant, Newborn; Liver; Male; Neonatal Abstinence Syndrome; Neuralgia; Oxycodone; Polymorphism, Genetic; Pregnancy; Receptors, Opioid, mu; Sex Characteristics
PubMed: 30652261
DOI: 10.1007/s40262-018-00731-3 -
Tidsskrift For Den Norske Laegeforening... May 2020Inadequate pain relief after caesarean section is a topic of international concern. At Oslo University Hospital, Ullevål, patients receive bupivacaine infiltration...
BACKGROUND
Inadequate pain relief after caesarean section is a topic of international concern. At Oslo University Hospital, Ullevål, patients receive bupivacaine infiltration local anaesthesia as well as oral paracetamol, ibuprofen and oxycodone for pain management during the first 24 hours post-surgery. The aim of this study was to survey pain after acute and elective caesarean sections in our department.
MATERIAL AND METHOD
The study included 50 patients who had undergone acute or elective caesarean section. Pain intensity on an 11-point numerical scale, pain duration, degree of mobilisation, and use of analgesia on postoperative day one were obtained from patient interviews and medical records.
RESULTS
Inadequate pain relief was defined as an average pain intensity of ≥ 4 and was reported by 34 patients (68 %). Total opioid consumption on postoperative day one exceeded 40 mg oral oxycodone equivalents in 28 patients. Of these, seven patients received more than 60 mg oral oxycodone equivalents.
INTERPRETATION
A large proportion of patients had high pain intensity and opioid requirement in the first 24 hours after caesarean section.
Topics: Analgesics, Opioid; Cesarean Section; Female; Humans; Oxycodone; Pain Management; Pain, Postoperative; Pregnancy
PubMed: 32378860
DOI: 10.4045/tidsskr.19.0506 -
Cellular and Molecular Neurobiology Jul 2021It is estimated that nearly a third of people who abuse drugs started with prescription opioid medicines. Approximately, 11.5 million Americans used prescription drugs... (Review)
Review
It is estimated that nearly a third of people who abuse drugs started with prescription opioid medicines. Approximately, 11.5 million Americans used prescription drugs recreationally in 2016, and in 2018, 46,802 Americans died as the result of an opioid overdose, including prescription opioids, heroin, and illicitly manufactured fentanyl (National Institutes on Drug Abuse (2020) Opioid Overdose Crisis. https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis . Accessed 06 June 2020). Yet physicians will continue to prescribe oral opioids for moderate-to-severe pain in the absence of alternative therapeutics, underscoring the importance in understanding how drug choice can influence detrimental outcomes. One of the opioid prescription medications that led to this crisis is oxycodone, where misuse of this drug has been rampant. Being one of the most highly prescribed opioid medications for treating moderate-to-severe pain as reflected in the skyrocketed increase in retail sales of 866% between 1997 and 2007, oxycodone was initially suggested to be less addictive than morphine. The false-claimed non-addictive formulation of oxycodone, OxyContin, further contributed to the opioid crisis. Abuse was often carried out by crushing the pills for immediate burst release, typically by nasal insufflation, or by liquefying the pills for intravenous injection. Here, we review oxycodone pharmacology and abuse liability as well as present the hypothesis that oxycodone may exhibit a unique pharmacology that contributes to its high likability and abuse susceptibility. We will discuss various mechanisms that likely contribute to the high abuse rate of oxycodone including clinical drug likability, pharmacokinetics, pharmacodynamics, differences in its actions within mesolimbic reward circuity compared to other opioids, and the possibility of differential molecular and cellular receptor interactions that contribute to its selective effects. We will also discuss marketing strategies and drug difference that likely contributes to the oxycodone opioid use disorders and addiction.
Topics: Analgesics, Opioid; Animals; Behavior, Addictive; Humans; Opioid Epidemic; Opioid-Related Disorders; Oxycodone; Pain; Reward
PubMed: 33245509
DOI: 10.1007/s10571-020-01013-y -
Missouri Medicine 2019
Topics: Drug Industry; Drug Overdose; Humans; Ownership; Oxycodone
PubMed: 31040484
DOI: No ID Found -
Anesthesiology Clinics Jun 2017Oxycodone, a semisynthetic opioid analgesic, is widely used in clinical practice. Oxycodone and morphine seem to be equally effective and equipotent; however, morphine... (Review)
Review
Oxycodone, a semisynthetic opioid analgesic, is widely used in clinical practice. Oxycodone and morphine seem to be equally effective and equipotent; however, morphine is 10 times more potent than oxycodone when given epidurally. This article provides an updated review of the basic pharmacology of oxycodone with a special focus on pharmacokinetic/pharmacodynamics properties. The controversy regarding oxycodone-mediated effects for visceral pain via agonism and the possible role of peripheral opioid analgesia are discussed in the present investigation in an attempt to propose a plausible explanation to the perplexing question of oxycodone analgesia.
Topics: Abdominal Pain; Analgesia; Analgesia, Patient-Controlled; Analgesics, Opioid; Cancer Pain; Humans; Morphine; Oxycodone; Pain; Pain Measurement
PubMed: 28526158
DOI: 10.1016/j.anclin.2017.01.022 -
Scandinavian Journal of Gastroenterology 2015Opioid-induced constipation (OIC) is a very troublesome, difficult to manage and a nearly universal complication of chronic opioid use to control pain associated with... (Review)
Review
Opioid-induced constipation (OIC) is a very troublesome, difficult to manage and a nearly universal complication of chronic opioid use to control pain associated with advanced illness. Some studies have reported that OIC is so intolerable in some patients that they skip their opioid medications and bear pain instead of OIC. Laxatives have commonly been used as a prophylaxis and treatment of OIC but they are frequently ineffective because the commonly available laxatives do not target the underlying mechanism of OIC, which is the blockade of peripheral mu-receptors. Recently, there have been a number of advances in the treatment of OIC, which any physician involved with opioid-prescribing discipline should be aware of. This review will update the new options and strategies available for treating OIC along with the relevant clinical trials. Finally, this review also provides a recommendation on the preferred way to approach a patient with OIC in the modern era as well as highlight on the importance of doctor-patient communication in this setting.
Topics: Chloride Channel Agonists; Chronic Pain; Constipation; Humans; Laxatives; Lubiprostone; Naloxone; Oxycodone; Peptides; Phenols; Receptors, Opioid, mu; Tapentadol
PubMed: 26061717
DOI: 10.3109/00365521.2015.1054423 -
The Cochrane Database of Systematic... Feb 2015Many patients with cancer experience moderate to severe pain that requires treatment with strong opioids, of which oxycodone and morphine are examples. Strong opioids... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many patients with cancer experience moderate to severe pain that requires treatment with strong opioids, of which oxycodone and morphine are examples. Strong opioids are, however, not effective for pain in all patients, nor are they well-tolerated by all patients. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for patients with cancer pain.
OBJECTIVES
To assess the effectiveness and tolerability of oxycodone for pain in adults with cancer.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), EMBASE (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), PsycINFO (Ovid) and PubMed to March 2014. We also searched Clinicaltrials.gov, metaRegister of Controlled Trials (mRCT), EU Clinical Trials Register and World Health Organization International Clinical Trials Registry Platform (ICTRP). We checked the bibliographic references of relevant identified studies and contacted the authors of the included studies to find additional trials not identified by the electronic searches. No language, date or publication status restrictions were applied to the search.
SELECTION CRITERIA
We included randomised controlled trials (parallel-group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted study data (study design, participant details, interventions and outcomes) and independently assessed the quality of the included studies according to standard Cochrane methodology. Where possible, we meta-analysed the pain intensity data using the generic inverse variance method, otherwise these data were summarised narratively along with the adverse event and patient preference data. The overall quality of the evidence for each outcome was assessed according to the GRADE approach.
MAIN RESULTS
We included 17 studies which enrolled/randomised 1390 patients with 1110 of these analysed for efficacy and 1170 for safety. The studies examined a number of different drug comparisons. Four studies compared controlled release (CR) oxycodone to immediate release (IR) oxycodone and pooled analysis of three of these studies showed that the effects of CR and IR oxycodone on pain intensity after treatment were similar (standardised mean difference (SMD) 0.1, 95% confidence interval (CI) -0.06 to 0.26; low quality evidence). This was in line with the finding that none of the included studies reported differences in pain intensity between the treatment groups. Three of the four studies also found similar results for treatment acceptability and adverse events in the IR and CR groups; but one study reported that, compared to IR oxycodone, CR oxycodone was associated with significantly fewer adverse events.Six studies compared CR oxycodone to CR morphine and pooled analysis of five of these studies indicated that pain intensity did not differ significantly between the treatments (SMD 0.14, 95% CI -0.04 to 0.32; low quality evidence). There were no marked differences in adverse event rates, treatment acceptability or quality of life ratings.The remaining seven studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None of them found any clear superiority or inferiority of oxycodone for cancer pain, neither as an analgesic agent nor in terms of adverse event rates and treatment acceptability.The quality of this evidence base was limited by the risk of bias of the studies and by small sample sizes for many outcomes. Random sequence generation and allocation concealment were under-reported, and the results were substantially compromised by attrition with data missing from more than 20% of the enrolled/randomised patients for efficacy and from more than 15% for safety.
AUTHORS' CONCLUSIONS
Overall, the data included within this review suggest that oxycodone offers similar levels of pain relief and adverse events to other strong opioids including morphine, which is commonly considered the gold standard strong opioid. Our conclusions are consistent with other recent reviews and suggest that while the reliability of the evidence base is low, given the absence of important differences within this analysis it seems unlikely that larger head to head studies of oxycodone versus morphine will be justified. This means that for clinical purposes oxycodone or morphine can be used as first line oral opioids for relief of cancer pain.
Topics: Analgesics, Opioid; Delayed-Action Preparations; Drug Administration Schedule; Humans; Morphine; Neoplasms; Oxycodone; Pain; Pain Management; Randomized Controlled Trials as Topic
PubMed: 25723351
DOI: 10.1002/14651858.CD003870.pub5 -
Pain Research & Management 2020Radiotherapy is commonly used to treat cancer patients. Besides the curable effect, radiotherapy also could relieve the pain of cancer patients. However, cancer pain is... (Review)
Review
Radiotherapy is commonly used to treat cancer patients. Besides the curable effect, radiotherapy also could relieve the pain of cancer patients. However, cancer pain is gradually alleviated about two weeks after radiotherapy. In addition, cancer patients who receive radiotherapy may also suffer from pain flare or radiotherapy-induced side effects such as radiation esophagitis, enteritis, and mucositis. Pain control is reported to be inadequate during the whole course of radiotherapy (before, during, and after radiotherapy), and quality of life is seriously affected. Hence, radiotherapy is suggested to be combined with analgesic drugs in clinical guidelines. Previous studies have shown that radiotherapy combined with oxycodone hydrochloride can effectively alleviate cancer pain. In this review, we firstly presented the necessity of analgesia during the whole course of radiotherapy. We also sketched the role of oxycodone hydrochloride in radiotherapy of bone metastases and radiotherapy-induced oral mucositis. Finally, we concluded that oxycodone hydrochloride shows good efficacy and tolerance and could be used for pain management before, during, and after radiotherapy.
Topics: Analgesics, Opioid; Female; Humans; Male; Oxycodone; Pain; Pain Management; Quality of Life; Radiation Injuries
PubMed: 32089760
DOI: 10.1155/2020/7565962 -
Journal of Dentistry Oct 2022Dental pain is a commonly managed presentation in medicine and dentistry, where oxycodone is often prescribed. The aim of this systematic review and meta-analysis was to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Dental pain is a commonly managed presentation in medicine and dentistry, where oxycodone is often prescribed. The aim of this systematic review and meta-analysis was to determine and quantify the effectiveness of oxycodone for acute dental pain.
DATA
Randomised controlled trials, controlled trials and comparative studies were included involving patients >12 years, where oxycodone was trialled for dental pain.
SOURCES
Three databases were searched: Medline Ovid, Embase Ovid and Web of Science. Two authors independently screened title and abstracts for relevance, extracted data and performed bias assessments.
STUDY SELECTION
Of 148 potentially relevant studies, 13 articles met the inclusion criteria for the systematic review and of the 13, nine studies were included in the meta-analysis. All studies were single-dose analgesia for surgical third molar extractions.
CONCLUSIONS
Oxycodone produced more effective analgesia in combination with paracetamol. In the meta-analysis, monotherapy etoricoxib and rofecoxib showed significant pain relief compared to combination oxycodone/paracetamol (SPID6 mean difference=-2.13, CI=-3.29, -0.98; TOTPAR6 mean difference=-2.98, CI=-4.90, -1.06). Non-steroidal anti-inflammatory drugs (NSAIDs) were more effective than oxycodone/paracetamol combinations, however, the evidence would become weak in a future study with a similar patient setting due to substantial statistical heterogeneity (SPID6 and TOTPAR6 prediction interval -4.471, 0.207 and -7.28, 1.32 respectively).
CLINICAL SIGNIFICANCE
Non-steroidal anti-inflammatory drugs were superior than oxycodone/paracetamol combinations, although some patient populations may experience similar effects to the combined oxycodone/paracetamol combination.
Topics: Acetaminophen; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Etoricoxib; Humans; Oxycodone; Pain, Postoperative
PubMed: 35977697
DOI: 10.1016/j.jdent.2022.104254 -
The Cochrane Database of Systematic... Aug 2017Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not effective for pain in all people, neither are they well-tolerated by all people. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for adults with cancer pain. This is an updated version of the original Cochrane review published in 2015, Issue 2 on oxycodone for cancer-related pain.
OBJECTIVES
To assess the effectiveness and tolerability of oxycodone by any route of administration for pain in adults with cancer.
SEARCH METHODS
For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), Embase (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), and PsycINFO (Ovid) to November 2016. We also searched four trial registries, checked the bibliographic references of relevant studies, and contacted the authors of the included studies. We applied no language, date, or publication status restrictions.
SELECTION CRITERIA
We included randomised controlled trials (parallel group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults by examining pain intensity/relief, adverse events, quality of life, and participant preference.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the included studies using standard Cochrane methodology. We meta-analysed pain intensity data using the generic inverse variance method, and adverse events using the Mantel-Haenszel method, or summarised these data narratively along with the quality of life and participant preference data. We assessed the overall quality of the evidence using GRADE.
MAIN RESULTS
For this update, we identified six new studies (1258 participants) for inclusion. In total, we included 23 studies which enrolled/randomised 2648 participants, with 2144 of these analysed for efficacy and 2363 for safety. The studies examined a number of different drug comparisons.Pooled analysis of three of the four studies comparing controlled-release (CR) oxycodone to immediate-release (IR) oxycodone showed that the ability of CR and IR oxycodone to provide pain relief were similar (standardised mean difference (SMD) 0.1, 95% confidence interval (CI) -0.06 to 0.26; low quality evidence). Pooled analyses of adverse events showed no significant differences between CR and IR oxycodone for asthenia (risk ratio (RR) 0.58, 95% CI 0.2 to 1.68), confusion (RR 0.78, 95% CI 0.2 to 3.02), constipation (RR 0.71, 95% CI 0.45 to 1.13), dizziness/lightheadedness (RR 0.74, 95% CI 0.4 to 1.37), drowsiness/somnolence (RR 1.03, 95% CI 0.69 to 1.54), dry mouth (RR 1.14, 95% CI 0.48 to 2.75), insomnia (RR 1.04, 95% CI 0.31 to 3.53), nausea (RR 0.85, 95% CI 0.56 to 1.28), nervousness (RR 0.57, 95% CI 0.2 to 1.64), pruritus (RR 1.46, 95% CI 0.65 to 3.25), vomiting (RR 0.66, 95% CI 0.38 to 1.15), and discontinuation due to adverse events (RR 0.6, 95% CI 0.29 to 1.22). The quality of the evidence was very low for all these adverse events. Three of the four studies found similar results for treatment acceptability.Pooled analysis of seven of the nine studies comparing CR oxycodone to CR morphine indicated that pain relief was significantly better after treatment with CR morphine than CR oxycodone (SMD 0.14, 95% CI 0.01 to 0.27; low quality evidence). However, sensitivity analysis did not corroborate this result (SMD 0.12, 95% CI -0.02 to 0.26).Pooled analyses of adverse events showed no significant differences between CR oxycodone and CR morphine for confusion (RR 1.01 95% CI 0.78 to 1.31), constipation (RR 0.98, 95% CI 0.82 to 1.16), dizziness/lightheadedness (RR 0.76, 95% CI 0.33 to 1.76), drowsiness/somnolence (RR 0.9, 95% CI 0.75 to 1.08), dry mouth (RR 1.01, 95% CI 0.8 to 1.26), dysuria (RR 0.71, 95% CI 0.4 to 1.26), nausea (RR 1.02, 95% CI 0.82 to 1.26), pruritus (RR 0.81, 95% CI 0.51 to 1.29), vomiting (RR 0.94, 95% CI 0.68 to 1.29), and discontinuation due to adverse events (RR 1.06, 95% CI 0.43 to 2.6). However, the RR for hallucinations was significantly lower after treatment with CR oxycodone compared to CR morphine (RR 0.52, 95% CI 0.28 to 0.97). The quality of the evidence was very low for all these adverse events. There were no marked differences in treatment acceptability or quality of life ratings.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 for cancer pain, neither as an analgesic agent nor in terms of adverse event rates and treatment acceptability.The quality of this evidence base was limited by the high or unclear risk of bias of the studies and by imprecision due to low or very low event rates or participant numbers for many outcomes.
AUTHORS' CONCLUSIONS
The conclusions have not changed since the previous version of this review. The data suggest that oxycodone offers similar levels of pain relief and overall adverse events to other strong opioids including morphine. Although we identified a clinically insignificant benefit on pain relief in favour of CR morphine over CR oxycodone, this did not persist following sensitivity analysis and so we do not consider this important. However, in this updated analysis, we found that hallucinations occurred less often 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 while the reliability of the evidence base is low, given the absence of important differences within this analysis it seems unlikely that larger head to head studies of oxycodone versus morphine are justified, although well-designed trials comparing oxycodone to other strong analgesics may well be useful. For clinical purposes, oxycodone or morphine can be used as first-line oral opioids for relief of cancer pain in adults.
Topics: Aged; Analgesics, Opioid; Cancer Pain; Constipation; Delayed-Action Preparations; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Morphine; Nausea; Neoplasms; Oxycodone; Pain Measurement; Quality of Life; Randomized Controlled Trials as Topic; Sleep Stages; Vomiting
PubMed: 28829910
DOI: 10.1002/14651858.CD003870.pub6