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CNS Drugs Jun 2015An oral, fixed-dose combination of prolonged-release (PR) oxycodone with PR naloxone (Targin(®), Targiniq(®), Targinact(®); hereafter referred to as... (Review)
Review
An oral, fixed-dose combination of prolonged-release (PR) oxycodone with PR naloxone (Targin(®), Targiniq(®), Targinact(®); hereafter referred to as oxycodone/naloxone PR) is approved in Europe for the second-line symptomatic treatment of patients with severe to very severe idiopathic restless legs syndrome (RLS), after failure of dopaminergic therapy. Coadministration of naloxone represents a targeted approach to counteracting opioid-induced bowel dysfunction without compromising therapeutic efficacy; because of its very low oral bioavailability, naloxone blocks the action of oxycodone at opioid receptors locally in the gut. The efficacy of oxycodone/naloxone PR in patients with severe RLS inadequately controlled by previous (mainly dopaminergic) treatment has been demonstrated in RELOXYN, a 12-week, randomized, double-blind study with a 40-week open-label extension. In this pivotal study, oxycodone/naloxone PR significantly improved RLS symptoms compared with placebo from week 2 onwards; a beneficial effect of oxycodone/naloxone PR was maintained through 1 year of treatment. Furthermore, improvements in RLS symptoms in oxycodone/naloxone PR recipients were accompanied by similarly sustained improvements in disease-specific quality of life and subjective sleep variables. Oxycodone/naloxone PR was generally well tolerated, with a treatment-related adverse event profile (e.g. gastrointestinal disorders, CNS disorders, fatigue and pruritus) that was consistent with that expected for opioid therapy. Notably, there were no confirmed cases of augmentation among oxycodone/naloxone PR recipients throughout the course of the study. Results from the well-designed RELOXYN trial have thus demonstrated the value of oxycodone/naloxone PR as a second-line therapy for severe refractory RLS; further investigation of this combination product as a first-line treatment for severe RLS is now warranted.
Topics: Central Nervous System Agents; Drug Combinations; Humans; Naloxone; Oxycodone; Restless Legs Syndrome
PubMed: 26135898
DOI: 10.1007/s40263-015-0254-y -
Current Medical Research and Opinion Jan 2008Oxycodone is a strong opioid that acts at mu- and kappa-opioid receptors. It has pharmacological actions similar to strong opioids, but with a specific pharmacologic... (Review)
Review
BACKGROUND
Oxycodone is a strong opioid that acts at mu- and kappa-opioid receptors. It has pharmacological actions similar to strong opioids, but with a specific pharmacologic profile and greater analgesic potency to morphine. The efficacy of oxycodone in managing neuropathic and somatic pain, both of malignant and non-malignant origin, has been established in a wide range of settings.
SCOPE
This review aims to provide a comprehensive evaluation of oxycodone and its role within clinical settings in order to provide an evidence-based perspective on its use in the clinic. Literature searches using Medline, EMBASE and Cochrane Databases were used to compile data for review. The review provides information on the pharmacokinetics and pharmacodynamics of oxycodone and also profiles established clinical data in neuropathic and somatic pain as well as emerging data to support the use of oxycodone in visceral pain, which may be due to its interaction with kappa-opioid receptors. Oxycodone is available in a range of formulations for oral, intraspinal and parenteral administration.
FINDINGS
The prolonged-release form of oxycodone offers a fast onset of analgesia, controlling pain for 12 hours and providing clinically meaningful relief of moderate to severe pain and improving quality of life across a broad spectrum of pain types.
CONCLUSIONS
Oxycodone provides significant pain relief. It has relevant points of difference from other opioids and as such may be a suitable alternative to morphine.
Topics: Age Factors; Analgesics, Opioid; Animals; Diabetic Neuropathies; Drug Evaluation; Humans; Immune Tolerance; Liver Failure; Metabolic Clearance Rate; Neoplasms; Oxycodone; Pain; Receptors, Opioid, mu; Renal Insufficiency; Sex Characteristics; Treatment Outcome
PubMed: 18039433
DOI: 10.1185/030079908x253708 -
Current Drug Targets Jan 2014Common opioids adverse effects include opioid-induced bowel dysfunction (OIBD), which comprises opioid-induced constipation, dry mouth, nausea, vomiting, gastric stasis,... (Review)
Review
INTRODUCTION
Common opioids adverse effects include opioid-induced bowel dysfunction (OIBD), which comprises opioid-induced constipation, dry mouth, nausea, vomiting, gastric stasis, bloating, and abdominal pain. Traditional laxatives which are often prescribed for the prevention and treatment of OIBD possess limited efficacy and display adverse effects. A targeted approach to OIBD management is the use of a combination of an opioid agonist with opioid receptor antagonist or administration of purely peripherally acting opioid receptor antagonists.
METHODS
A literature search with terms "oxycodone/naloxone" in the PubMed and MEDLINE database updated on 31(st) July 2013. All studies of oxycodone/naloxone (randomized, controlled trials and open, uncontrolled studies) were included. In addition, studies on pharmacokinetics and pharmacodynamics of oxycodone/naloxone were included.
RESULTS
A combination of prolonged-release oxycodone with prolonged-release naloxone (OXN) in one tablet with a fixed 2:1 ratio provides effective analgesia with limited disturbing effect on bowel function. Oxycodone is a valued opioid administered either as the first strong opioid or when other strong opioids have been ineffective. Naloxone is an opioid receptor antagonist that displays local antagonist effect on opioid receptors in the gastrointestinal tract and is nearly completely inactivated in the liver after oral administration. As demonstrated in controlled studies conducted in patients with chronic non-malignant and cancer-related pain OXN in daily doses up to 80 mg/40 mg provided equally effective analgesia with an improved bowel function compared to oxycodone administered alone.
CONCLUSION
OXN is an important drug for chronic pain management, prevention and treatment of OIBD.
Topics: Constipation; Drug Combinations; Gastrointestinal Tract; Humans; Naloxone; Oxycodone; Pain
PubMed: 24020972
DOI: 10.2174/13894501113149990210 -
Trends in Pharmacological Sciences Apr 2013Oxycodone is a semisynthetic opioid analgesic that is increasingly used for the treatment of acute, cancer, and chronic non-malignant pain. Oxycodone was synthesized in... (Review)
Review
Oxycodone is a semisynthetic opioid analgesic that is increasingly used for the treatment of acute, cancer, and chronic non-malignant pain. Oxycodone was synthesized in 1917 but its pharmacological properties were not thoroughly studied until recently. Oxycodone is a fairly selective μ-opioid receptor agonist, but there is a striking discrepancy between the relatively low binding potential and G protein activation by oxycodone and its analgesic efficacy. It has been claimed that this is because of active metabolites and enhanced passage to the central nervous system by active transport. We critically review studies on the basic pharmacology of oxycodone and on its pharmacokinetics and pharmacodynamics in humans. In particular, the role of pharmacogenomics and population pharmacokinetics in understanding the properties of oxycodone is discussed in detail. We compare oxycodone with morphine, the standard opioid in clinical use.
Topics: Analgesics, Opioid; Animals; Humans; Oxycodone; Receptors, Opioid, mu
PubMed: 23465410
DOI: 10.1016/j.tips.2013.02.001 -
The Medical Letter on Drugs and... Sep 2018
Review
Topics: Abuse-Deterrent Formulations; Analgesics, Opioid; Animals; Cross-Over Studies; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Oxycodone
PubMed: 30383730
DOI: No ID Found -
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 -
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 -
Acta Crystallographica. Section C,... Nov 2012The title compound, (5R,9R,13S,14S,17R)-14-hydroxy-3-methoxy-17-methyl-4,5-epoxymorphinan-6-one N-oxide, C(18)H(21)NO(5), has been prepared in a diastereomerically pure...
The title compound, (5R,9R,13S,14S,17R)-14-hydroxy-3-methoxy-17-methyl-4,5-epoxymorphinan-6-one N-oxide, C(18)H(21)NO(5), has been prepared in a diastereomerically pure form by the reaction of oxycodone with 3-chloroperbenzoic acid and subsequent crystallization of the product from chloroform. The crystal packing shows that the molecule exhibits intramolecular O-H···O [D···A = 2.482 (2) Å] hydrogen bonding. In addition, there are weak intermolecular C-H...O interactions which, along with van der Waals forces, stabilize the structure. The new chiral center at the 17-position is demonstrated to be R.
Topics: Chlorobenzoates; Crystallography, X-Ray; Hydrogen Bonding; Molecular Structure; Oxycodone
PubMed: 23124457
DOI: 10.1107/S0108270112040188 -
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 -
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