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Clinical & Translational Oncology :... May 2007Oxycodone is a semi-synthetic opioid with an agonist activity on mu, kappa and delta receptors. Equivalence with regard to morphine is 1:2. Its effect commences one hour... (Review)
Review
Oxycodone is a semi-synthetic opioid with an agonist activity on mu, kappa and delta receptors. Equivalence with regard to morphine is 1:2. Its effect commences one hour after administration and lasts for 12 h in the controlled-release formulation. Plasma halflife is 3-5 h (half that of morphine) and stable plasma levels are reached within 24 h (2-7 days for morphine). Oral bioavailability ranges from 60 to 87%, and plasma protein binding is 45%. Most of the drug is metabolised in the liver, while the rest is excreted by the kidney along with its metabolites. The two main metabolites are oxymorphone--which is also a very potent analgesic--and noroxycodone, a weak analgesic. Oxycodone metabolism is more predictable than that of morphine, and therefore titration is easier. Oxycodone has the same mechanism of action as other opioids: binding to a receptor, inhibition of adenylyl-cyclase and hyperpolarisation of neurons, and decreased excitability. These mechanisms also play a part in the onset of dependence and tolerance. The clinical efficacy of oxycodone is similar to that of morphine, with a ratio of 1/1.5-2 for the treatment of cancer pain. Long-term administration may be associated with less toxicity in comparison with morphine. In the future, both opioids could be used simultaneously at low doses to reduce toxicity. It does not appear that there are any differences between immediate and slow-release oxycodone, except their half-life is 3-4 h, and 12 h, respectively. In Spain, controlled-release oxycodone (OxyContin) is marketed as 10-, 20-, 40- or 80-mg tablets for b.i.d. administration. Tablets must be taken whole and must not be broken, chewed or crushed. There is no food interference. The initial dose is 10 mg b.i.d. for new treatments and no dose reduction is needed in the elderly or in cases of moderate hepatic or renal failure. Immediate-release oxycodone (OxyNorm) is also available in capsules and oral solution. Side effects are those common to opioids: mainly nausea, constipation and drowsiness. Vomiting, pruritus and dizziness are less common. The intensity of these side effects tends to decrease over the course of time. Oxycodone causes somewhat less nausea, hallucinations and pruritus than morphine.
Topics: Analgesics, Opioid; Humans; Oxycodone; Pain
PubMed: 17525040
DOI: 10.1007/s12094-007-0057-9 -
PloS One 2022This study aims to evaluate the efficacy and safety of oxycodone hydrochloride (OxyContin) rectal administration in cancer pain patients. This is geared towards... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aims to evaluate the efficacy and safety of oxycodone hydrochloride (OxyContin) rectal administration in cancer pain patients. This is geared towards providing the research evidence for a novel route of OxyContin administration.
METHODS
Relevant randomized controlled trials (RCTs) were searched in electronic databases, including PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wanfang Data Knowledge Service Platform, and Chinese Biomedical Literature Database (CBM). Moreover, unpublished academic data were obtained by contacting the colleague, professor, or Institute of Traditional Chinese Medicine. The RCTs of transrectal Oxycodone administration of sustained-release tablets for moderate and severe pain patients were searched in the databases from inception to December 2020.
RESULTS
According to the inclusion criteria, a total of 8 RCTs were included, with a total of 648 patients. Meta analysis results showed that there was no statistically significant difference in the efficacy of moderate to severe pain control between the rectal administration group and the oral administration group (RR = 1.04, 95%CI: 0.99-1.10, p = 0.13>0.05). At the same time, the incidence of adverse reactions in the rectal administration group was low. In terms of constipation, the rectal administration group was less than the oral administration group, with a statistically significant difference (RR = 0.43, 95%CI: 0.31-0.58, p< 0.00001). In terms of nausea and vomiting, the rectal administration group was less than the oral administration group, and the difference was statistically significant(RR = 0.30, 95%CI: 0.21-0.42, p<0.00001). In terms of sleepiness, there was no significant difference between the two groups(RR = 0.54, 95%CI: 0.26-1.15, p = 0.11>0.05). In terms of dizziness, there was no statistically significant difference between the two groups (RR = 0.43, 95%CI:0.27-0.68, p = 0.31>0.05). In terms of dyuria, there was no statistically significant difference between the two groups (RR = 0.37, 95%CI: 0.02-7.02, p = 0.51>0.05). In terms of KPS scores there was no significant difference was noted between the rectal and oral administration groups (RR = 1.04, 95%CI: 0.89-1.21, p = 0.63>0.05).
CONCLUSION
In summary, we found no significant differences in efficacy between rectal administration of OxyContin and oral administration. Thus, rectal administration should be considered in managing cancer pain among patients with difficulty in oral OxyContin administration.
PROSPERO REGISTRATION NUMBER
CRD42021209660.
Topics: Administration, Rectal; Cancer Pain; Delayed-Action Preparations; Humans; Oxycodone; Pain
PubMed: 35759471
DOI: 10.1371/journal.pone.0266754 -
Medicine Jun 2017Problems like body movement, respiratory depression, and complained of pain are still common phenomenon in outpatient artificial abortion general anesthesia. Oxycodone... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Problems like body movement, respiratory depression, and complained of pain are still common phenomenon in outpatient artificial abortion general anesthesia. Oxycodone hydrochloride is a semisynthetic opioid and has a good therapeutic effect on visceral pain. We hypothesize that oxycodone hydrochloride would be superior to fentanyl in outpatient artificial abortion surgery.
METHODS
In this clinical trial 149 American Society of Anesthesiologists (ASA) I or II female outpatients scheduled for elective artificial abortion surgeries under general anesthesia were randomly divided into 3 groups: oxycodone hydrochloride 0.06 mg/kg group (group A), oxycodone hydrochloride 0.08 mg/kg group (group B), and control group fentanyl 2 ug/kg (group C). The primary outcome was level body movement and respiratory depression during the surgery, the second outcome included the visual analogue scale (VAS) score 30 minutes after waking.
RESULTS
A total of 120 participants completed the study, n = 40 in each group. There was no significant difference in patients' age, body mass index (BMI), preoperative heart rate, mean arterial blood pressure, consumption dose of propofol, intraoperative body movement type and times, and duration of surgery among the 3 groups (P > .05). Comparing the incidence of intraoperative respiratory depression and SPO2 < 90% among the 3 groups, group C's was significantly higher than those of groups A and B, and the difference was statistically significant (P < .05). Group A had no difference compared with group B. In VAS score 30minutes after waking, group C was the highest, followed by group A, with group B as the lowest. The difference among the 3 groups was statistically significant (P < .05), but a difference delta less than 1 on the VAS scale is not clinically significant.
CONCLUSION
The analgesic effect of oxycodone hydrochloride at 0.06 mg/kg applied to painless artificial abortion surgery is not superior than that of fentanyl, but the incidence of intraoperative respiratory depression and hypoxemia is significantly lower than fentanyl.
Topics: Abortion, Induced; Adult; Ambulatory Surgical Procedures; Analgesics, Opioid; Anesthesia, General; Female; Fentanyl; Humans; Hypoxia; Outpatients; Oxycodone; Pain Measurement; Pain, Postoperative; Respiration; Treatment Outcome
PubMed: 28658164
DOI: 10.1097/MD.0000000000007376 -
The American Journal of Nursing Jan 2004
Review
Topics: Acute Disease; Analgesics, Opioid; Chemistry, Pharmaceutical; Chronic Disease; Delayed-Action Preparations; Humans; Neoplasms; Oxycodone; Pain; Pain Measurement; Substance-Related Disorders; Treatment Outcome
PubMed: 14707810
DOI: 10.1097/00000446-200401000-00013 -
Clinical Therapeutics Jul 2012An immediate-release oxycodone hydrochloride formulation (IRO-A) indicated for moderate to severe pain was designed (by adding functional excipients) to discourage... (Comparative Study)
Comparative Study Randomized Controlled Trial
Dose proportionality and the effects of food on bioavailability of an immediate-release oxycodone hydrochloride tablet designed to discourage tampering and its relative bioavailability compared with a marketed oxycodone tablet under fed conditions: a single-dose, randomized, open-label, 5-way...
BACKGROUND
An immediate-release oxycodone hydrochloride formulation (IRO-A) indicated for moderate to severe pain was designed (by adding functional excipients) to discourage tampering associated with intranasal and intravenous abuse of prescription opioids.
OBJECTIVES
The primary objective of this study was to determine the dose proportionality of oxycodone in IRO-A tablets under fasted conditions. Secondary objectives were to assess food effects on the pharmacokinetics of IRO-A tablets, to compare the relative bioavailability of oxycodone in IRO-A tablets versus marketed oxycodone hydrochloride (IRO) tablets under fed conditions and to evaluate the single-dose safety profile of the IRO-A tablets in healthy volunteers pretreated with naltrexone.
METHODS
This open-label, single-dose, randomized, 5-way crossover study was conducted in healthy adults who received each of the following treatments, separated by a washout period of ≥7 days: IRO-A 1 × 5 mg, 2 × 5 mg, and 2 × 7.5 mg under fasted conditions, and IRO-A 2 × 7.5 mg and IRO 1 × 15 mg after a high-fat, high-calorie breakfast. Naltrexone was administered to minimize untoward pharmacologic effects of oxycodone. Dose proportionality (IRO-A), food effects (IRO-A), and relative bioavailability in a fed state (IRO-A and IRO) were assessed by using bioequivalence criteria (90% CIs between 80% and 125% for C(max) and AUC).
RESULTS
Of the 35 adults enrolled in the study, 33 completed at least 1 dosing period. Most participants were male (54%) and white (69%), with a mean (SD) age of 32.6 (11.1) years and mean weight of 75.5 (12.3) kg. Plasma levels of oxycodone in IRO-A suggested dose-proportional pharmacokinetics; 90% CIs for dose-normalized C(max), AUC(0-last), and AUC(0-∞) fell within the 80% to 125% range. Concomitant food intake with IRO-A resulted in an ~14% reduction in oxycodone C(max) and an ~21% increase in AUC(0-last). The bioavailability of oxycodone from IRO-A tablets in the fed state was comparable with IRO tablets based on AUC parameters, although C(max) was ~16.5% lower. Reported or observed treatment-emergent adverse events were monitored throughout the study and were similar for IRO-A and IRO tablets. Nausea, headache, abdominal pain, and dizziness were the most common and are consistent with known effects of oxycodone after naltrexone blockade.
CONCLUSIONS
Plasma levels of oxycodone in IRO-A tablets were compatible with proportional single-dose pharmacokinetics from 5 to 15 mg under fasted conditions. Administration of IRO-A with food suggested increased overall bioavailability relative to fasting conditions and a reduction in peak systemic exposure of oxycodone that is not expected to be clinically significant. When comparing IRO-A tablets with IRO tablets in the fed state, the overall systemic exposure of oxycodone was comparable, and peak systemic exposure was lower.
Topics: Adolescent; Adult; Analgesics, Opioid; Area Under Curve; Biological Availability; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Food-Drug Interactions; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Oxycodone; Tablets; Therapeutic Equivalency; Young Adult
PubMed: 22717418
DOI: 10.1016/j.clinthera.2012.05.009 -
Drugs Mar 2014A combination of prolonged-release (PR) oxycodone with PR naloxone (Targin(®), Targiniq(®), Targinact(®)) in one tablet with a fixed 2:1 ratio is available for the... (Review)
Review
A combination of prolonged-release (PR) oxycodone with PR naloxone (Targin(®), Targiniq(®), Targinact(®)) in one tablet with a fixed 2:1 ratio is available for the treatment of patients with severe pain, which can only be adequately managed with opioid analgesics. The aim of this formulation is to counteract opioid-induced constipation through the local antagonist effect of naloxone in the gut wall, while maintaining analgesia due to the low bioavailability of oral naloxone. Three large, 12-week, randomized, double-blind, phase III trials in patients with moderate to severe, chronic, non-malignant pain, plus a prospectively planned pooled analysis of two of these studies, demonstrated that oxycodone/naloxone PR improved bowel function, as measured by the bowel function index, compared with oxycodone PR. Additionally, oxycodone/naloxone PR relieved pain more effectively than placebo and no less effectively than oxycodone PR after 12 weeks. Phase II efficacy data in cancer patients are consistent with those observed in patients with non-malignant pain. Oxycodone/naloxone PR was generally well tolerated; the most frequently reported adverse events were of gastrointestinal origin, consistent with those known to occur with opioid therapy. Of note, numerically lower rates of constipation were observed in the oxycodone/naloxone PR group compared with the oxycodone PR group. A cost-utility analysis predicted that oxycodone/naloxone PR would be a cost-effective option compared with oxycodone PR in patients with non-malignant pain. Although more comparative data are needed, oxycodone/naloxone PR is an effective option for use in patients with severe chronic pain, particularly among those with opioid-induced constipation.
Topics: Analgesics, Opioid; Chronic Pain; Constipation; Delayed-Action Preparations; Drug Combinations; Drug Interactions; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Oxycodone; Quality of Life
PubMed: 24452879
DOI: 10.1007/s40265-014-0177-9 -
Clinical and Translational Science Sep 2021This study assessed the impact of product particle sizes (fine: 106-500 µm; coarse: 500-1000 µm) on oxycodone pharmacokinetics (PK) following nasal insufflation of... (Randomized Controlled Trial)
Randomized Controlled Trial
This study assessed the impact of product particle sizes (fine: 106-500 µm; coarse: 500-1000 µm) on oxycodone pharmacokinetics (PK) following nasal insufflation of milled oxycodone extended-release (ER) abuse-deterrent (AD) tablets using immediate-release (IR) non-AD product as reference. Additionally, this study assessed the effects of different excipient to drug ratio (EDR) by comparing two products with fine particle size but different EDRs, again using IR non-AD as the control. Thirty milligrams of oxycodone were administered in each treatment. Coarsely milled 30 mg ER tablets demonstrated significantly lower maximum plasma concentration (C ) and partial areas under the concentration-time curve (AUCs) than those of the finely milled IR tablets. Finely milled ER tablets demonstrated similar C and partial AUCs but higher total systemic exposures than those of finely milled IR tablets. Finely milled 80 mg ER tablets were bioequivalent to IR tablet on all parameters. The finely milled 30 mg ER tablet was not bioequivalent to the coarsely milled 30 mg ER tablet and had higher values for all parameters. The finely milled 30 mg ER tablets (EDR 6.9) showed no PK differences with finely milled 80 mg ER tablets (EDR 4.9). No serious adverse events were reported. The study demonstrated a significant effect of particle sizes (106-1000 µm) on PK of milled and insufflated oxycodone ER AD tablets. EDR difference did not have any significant effects on the PK of finely milled oxycodone ER AD tablets. Particle size distribution should be considered when nasal AD properties of opioid drug products are investigated during drug development.
Topics: Abuse-Deterrent Formulations; Administration, Intranasal; Adolescent; Adult; Analgesics, Opioid; Area Under Curve; Cross-Over Studies; Delayed-Action Preparations; Female; Healthy Volunteers; Humans; Insufflation; Male; Middle Aged; Opioid-Related Disorders; Oxycodone; Particle Size; Tablets; Young Adult
PubMed: 33982418
DOI: 10.1111/cts.13053 -
Minerva Anestesiologica 2005Opioids are widely used as effective analgesic therapy for cancer pain. Despite years of controversy, their use has been also accepted in chronic non-cancer pain.... (Review)
Review
Opioids are widely used as effective analgesic therapy for cancer pain. Despite years of controversy, their use has been also accepted in chronic non-cancer pain. Oxycodone alone and in combination has been used for over 80 years in the treatment of a variety of pain syndromes. As single agent, the controlled release (CR) oxycodone's market in the USA grew from 10% in 1996 to 53% in 2000 and it has become a leading opioid in the United States. Recent data showed that the fixed-combination oxycodone/acetaminophen (5 mg/325 mg) is the most often prescribed opioid across all the different chronic pain diagnoses. Compared with morphine, oxycodone has a higher oral bioavailability and is about twice as potent. Pharmacokinetic-pharmacodynamic data support oxycodone as a pharmacologically active opiod that does not require conversion to oxymoprhone for pharmacological activity. Seven studies addressed the safety and efficacy of oxycodone for the treatment of non-cancer pain (low back pain, osteoarthritis pain, and painful diabetic neuropathy). Both immediate release (IR) and CR oxycodone are equally effective and safe. Along these trials, mean daily dosage of oxycodone was approximately 40 mg, with a low incidence of intolerable typical opiate side effects. In cancer pain, oxycodone can be considered a valid alternative to oral morphine to be used for opioid rotation. No difference in analgesic efficacy between CR oxycodone and CR morphine was found. Controlled-release preparations, with a long duration of action, are attractive because they offer the advantage of longer dosing intervals and sustained analgesic effect.
Topics: Analgesics, Opioid; Chronic Disease; Clinical Trials as Topic; Delayed-Action Preparations; Humans; Neoplasms; Oxycodone; Pain
PubMed: 16012419
DOI: No ID Found -
Pharmacological Reports : PR 2010Oxycodone is a valued opioid analgesic, which may be administered either as the first strong opioid or when other strong opioids are ineffective. In case of insufficient... (Review)
Review
Oxycodone is a valued opioid analgesic, which may be administered either as the first strong opioid or when other strong opioids are ineffective. In case of insufficient analgesia and/or intense adverse effects such as sedation, hallucinations and nausea/vomiting a switch from another opioid to oxycodone might be beneficial. Oxycodone is administered to opioid-naive patients with severe pain and to patients who were unsuccessfully treated with weak opioids, namely tramadol, codeine and dihydrocodeine. Oxycodone effective analgesia may be attributed to its affinity to μ and possibly κ opioid receptors, rapid penetration through the blood-brain barrier and higher concentrations in brain than in plasma. Oxycodone displays high bioavailability after oral administration and may be better than morphine in patients with renal impairment due to the decreased production of active metabolites. Recently an oral controlled-release oxycodone formulation was introduced in Poland. Another new product that was launched recently is a combination of prolonged-release oxycodone with prolonged-release naloxone (oxycodone/naloxone tablets). The aim of this review is to outline the pharmacodynamic and pharmacokinetic properties, drug interactions, dosing rules, adverse effects, equianalgesic dose ratio with other opioids and clinical studies of oxycodone in patients with cancer pain. The potential role of oxycodone/naloxone in chronic pain management and its impact on the bowel function is also discussed.
Topics: Analgesics, Opioid; Animals; Delayed-Action Preparations; Drug Combinations; Drug Interactions; Humans; Naloxone; Narcotic Antagonists; Neoplasms; Oxycodone; Pain
PubMed: 20884999
DOI: 10.1016/s1734-1140(10)70316-9 -
Drugs May 2013In recent years the use of the opioid oxycodone has increased markedly and replacing morphine as the first-line choice of opioid in several countries. There are... (Review)
Review
In recent years the use of the opioid oxycodone has increased markedly and replacing morphine as the first-line choice of opioid in several countries. There are formulations for oral immediate, oral extended release and intravenous use. The bioavailability is higher than for morphine and less variable. Oxycodone is primarily metabolized in the liver by the cytochrome P450 (CYP) enzymes with CYP3A as the major metabolic pathway and CYP2D6 as the minor metabolic pathway to noroxycodone, oxymorphone and noroxymorphone. Oxycodone exerts its analgesic effect via the µ-opioid receptor. The metabolism of CYP2D6 substrates varies to a large degree between individuals as a result of allele functionality. Poor metabolizers (PM) have two non-functional alleles, extensive metabolizers (EM) are homozygous with two functional alleles or heterozygous with one functional allele and ultrarapid metabolizers (UM) have more than two functional alleles. There are pronounced interethnic differences in the allele distribution. On the basis of studies performed thus far, oxycodone concentrations in comparison with EM are similar in PM and reduced in UM. The pharmacokinetics in UM are insufficiently investigated. Simultaneous inhibition of both CYP3A and CYP2D6 results in increased oxycodone concentrations and such a combination should be avoided. A similar effect is to be expected with use of a CYP3A inhibitor in CYP2D6 PM. Concomitant use of enzyme inducers such as rifampicin, St John's wort and carbamazepine should be avoided because of the risk of subtherapeutic concentrations of oxycodone. When the dosage of morphine may result in unpredictable bioavailability, like in patients with severe hepatic cirrhosis, oxycodone might be beneficial because it has higher and less variability in bioavailability between patients than morphine.
Topics: Analgesics, Opioid; Animals; Clinical Trials as Topic; Cytochrome P-450 Enzyme System; Delayed-Action Preparations; Humans; Oxycodone
PubMed: 23605691
DOI: 10.1007/s40265-013-0036-0