Oxycodone

Oxycodone is a semisynthetic opioid synthesized from thebaine, an opioid

Oxycodone
alkaloid found in the Persian poppy, and one of the many alkaloids found
in the opium poppy. It is a moderately potent opioid pain medication
(orally roughly 1.5 times more potent than morphine),[8] generally
indicated for relief of moderate to severe pain.[9] Oxycodone was
developed in 1917 in Germany[10][11] as one of several semi-synthetic
[1]
opioids in an attempt to improve on the existing opioids.

Oxycodone is available as single-ingredient medication in immediate

release and controlled release. In the United Kingdom, it is available in
10 mg/mL and 50 mg/mL formulation for intramuscular or intravenous
administration.[12] Combination products are also available as immediate-
release formulations, with non-narcotic analgesic ingredients such as
paracetamol (acetaminophen) and nonsteroidal anti-inflammatory drugs
(NSAIDs), including aspirin and ibuprofen.

As it has euphoric effects similar to other opioids, oxycodone is one of the

drugs abused in the current opioid epidemic in the United States.[13][14]
An abuse-deterrent combination with naloxone is available in managed-
release tablets. If injected, the naloxone precipitates opioid withdrawal
symptoms and blocks the effect of the medication. However, there have Clinical data
been concerns raised about the effectiveness of the abuse prevention Trade names many
measures.[14][15] Synonyms Eukodal, eucodal;
dihydrohydroxycodeinone,
7,8-dihydro-14-
Contents hydroxycodeinone, 6-
deoxy-7,8-dihydro-14-
Medical uses
hydroxy-3-O-methyl-6-
Administration
oxomorphine[2]
Side effects
Dependence, addiction, and withdrawal
AHFS/Drugs.com Monograph
Hormone imbalance MedlinePlus a682132
Interactions Pregnancy AU: C
Pharmacodynamics category
US: B (No risk in non-
Controversy
human studies)
Pharmacokinetics
Absorption Dependence High
Distribution liability
Metabolism Routes of By mouth, sublingual,
Elimination administration intramuscular,
Bioavailability intravenous, intranasal,
Morphine equivalency
subcutaneous,
Chemistry transdermal, rectal,
Biosynthesis
epidural[1]
Detection in biological fluids
ATC code N02AA05 (WHO)
History
 Society and culture N02AA55 (WHO) (in
Legal status combinations)
Recreational use
Economics Legal status
Names Legal status AU: S8 (Controlled)
Available forms
CA: Schedule I
See also
DE: Anlage III (Special
References
prescription form
Further reading
required)
UK: Class A

Medical uses US: Schedule II

Oxycodone has been in clinical use since 1916,[1] and it is used for Pharmacokinetic data
managing moderate to moderately severe acute or chronic pain.[16] It has Bioavailability 60–87%[3][5]
been found to improve quality of life for those with many types of Protein binding 45%[3]
pain.[17] Experts are divided regarding use for non-cancer-related chronic
Metabolism Hepatic: mainly CYP3A,
pain, as most opioids have great potential for dependence and have also
and, to a much lesser
been alleged to createparadoxical pain sensitivity.
extent, CYP2D6 to
Oxycodone is available as controlled-release tablet, intended to be taken oxymorphone (~5%);[3]
every 12 hours.[18] A 2006 review found that controlled-release 95% metabolized (i.e., 5%
oxycodone is comparable to instant-release oxycodone, morphine, and excreted unchanged)[4]
hydromorphone in management of moderate to severe cancer pain, with Onset of action 10–30 minutes (IR)[5][4]
fewer side effects than morphine. The author concluded that the controlled 1 hour (CR)[6]
release form is a valid alternative to morphine and a first-line treatment for Biological half- 2–3 hours (IR) (variable)
cancer pain.[19] In 2014, the European Association for Palliative Care life (same t1/2 for all
recommended oral oxycodone as a second-line alternative to oral
ROAs)[5][4]
morphine for cancer pain.[20]
4.5 hours (CR)[7]
In the U.S., extended-release oxycodone is approved for use in children as Duration of 3–6 hours (IR) (variable)[4]
action 12 hours (CR)[6]
young as 11 years old. The approved indication is for relief of cancer pain,
trauma pain, or pain due to major surgery, in children already treated with Excretion Urine (83%)[3]
opioids, who can tolerate at least 20 mg per day of oxycodone; this
Identifiers
provides an alternative to Duragesic (fentanyl) the only other extended-
release opioid analgesic approved for children.[21]
IUPAC name
CAS Number 76-42-6
PubChem CID 5284603
Administration
In the United States, oxycodone is only approved for oral use, available as IUPHAR/BPS 7093
tablets and oral solutions. In Spain, the Netherlands and the United DrugBank DB00497
Kingdom, oxycodone is also approved for intravenous (IV) and
ChemSpider 4447649
intramuscular (IM) use. When first introduced in Germany during World
War I, both IV and IM administrations of oxycodone were commonly used UNII CD35PMG570
for postoperative pain management ofCentral Powers soldiers.[1]
KEGG D05312
ChEBI
Side effects CHEBI:7852
ChEMBL CHEMBL656
Serious side effects of oxycodone include reduced sensitivity to pain
(beyond the pain the drug is taken to reduce), euphoria, anxiolysis, ECHA InfoCard 100.000.874
feelings of relaxation, and respiratory depression.[23] Common side effects Chemical and physical data
of oxycodone include constipation (23%), nausea (23%), vomiting (12%), Formula C18H21NO4
somnolence (23%), dizziness (13%), itching (13%), dry mouth (6%), and Molar mass 315.364 g/mol
sweating (5%).[23][24] Less common side effects (experienced by less than
3D model Interactive image
5% of patients) include loss of appetite, nervousness, abdominal pain, (JSmol)
diarrhea, urine retention, dyspnea, and hiccups.[25] Solubility in HCl: 166 mg/mL (20 °C)
water
In high doses, overdoses, or in some persons not tolerant to opioids,
SMILES
oxycodone can cause shallow breathing, slowed heart rate, cold/clammy
skin, pauses in breathing, low blood pressure, constricted pupils, InChI
circulatory collapse, respiratory arrest, and death.[25] (verify)

Oxycodone overdose has also been described to cause spinal cord infarction
in high doses and ischemic damage to the brain, due to prolonged hypoxia
from suppressed breathing.[26]

Oxycodone in combination with naloxone in managed-release tablets, has

been formulated to both deter abuse and reduce "opioid-induced
Both sides of a single 10mg OxyContin pill.
constipation".[27]

Dependence, addiction, and withdrawal

The risk of experiencing severe withdrawal symptoms is high if a patient has
become physically dependent and discontinues oxycodone abruptly. Medically,
when the drug has been taken regularly over an extended period, it is withdrawn
gradually rather than abruptly. People who regularly use oxycodone recreationally or
at higher than prescribed doses are at even higher risk of severe withdrawal
symptoms. The symptoms of oxycodone withdrawal, as with other opioids, may
include "anxiety, panic attack, nausea, insomnia, muscle pain, muscle weakness,
fevers, and other flu-like symptoms".[28]

Withdrawal symptoms have also been reported in newborns whose mothers had been
.[29]
either injecting or orally taking oxycodone during pregnancy Main side effects of oxycodone[22]

Hormone imbalance
As with other opioids, chronic use of oxycodone (particularly with higher doses) often causes concurrent hypogonadism or hormone
imbalance.[30]

Interactions
Oxycodone is metabolized by the enzymes CYP3A4 and CYP2D6, and its clearance therefore can be altered by inhibitors and
inducers of these enzymes.[31] (For lists of CYP3A4 and CYP2D6 inhibitors and inducers, see here and here, respectively.) Natural
genetic variation in these enzymes can also influence the clearance of oxycodone, which may be related to the wide inter-individual
variability in its half-life and potency.[31]

Ritonavir or lopinavir/ritonavir greatly increase plasma concentrations of oxycodone in healthy human volunteers due to inhibition of
CYP3A4 and CYP2D6.[32] Rifampicin greatly reduces plasma concentrations of oxycodone due to strong induction of CYP3A4.[33]
There is also a case report of fosphenytoin, a CYP3A4 inducer, dramatically reducing the analgesic effects of oxycodone in a chronic
pain patient.[34] Dosage or medication adjustments may be necessary in each case.
[32][33][34]

Pharmacodynamics
Oxycodone is a highly selectivefull agonist of the μ-opioid receptor (MOR), with low affinity for the δ-opioid receptor (DOR) and κ-
opioid receptor (KOR).[35][31] After oxycodone binds to the MOR, a G protein-complex is released, which inhibits the release of
neurotransmitters by the cell by reducing the amount of cAMP produced, closing calcium channels, and opening potassium
channels.[36]

Compound[37] MOR (Ki) DOR (Ki) KOR (Ki) δ/μ (ratio) κ/μ (ratio)

Oxycodone 18 nM 958 nM 677 nM 53 38

Similarly to most other opioids, oxycodone increases prolactin secretion, but its influence on testosterone levels is unknown.[35]
Unlike morphine, oxycodone lacks immunosuppressive activity (measured by natural killer cell activity and interleukin 2 production
[35]
in vitro); the clinical relevance of this has not been clarified.

Controversy
In 1997, a group of Australian researchers proposed (based on a study in rats) that oxycodone acts on KORs, unlike morphine, which
acts upon MORs.[38] Further research by this group indicated the drug appears to be a κ2b-opioid agonist.[39] However, this
ef that are typical of μ-opioid agonists.[40]
conclusion has been disputed, primarily on the basis that oxycodone produces fects

In 2006, research by a Japanese group suggested the effect of oxycodone is mediated by different receptors in different situations.
Specifically in diabetic mice, the κ-opioid receptor appears to be involved in the antinociceptive effects of oxycodone,[41] while in
fects.[42]
nondiabetic mice, the μ1-opioid receptor seems to be primarily responsible for these ef

Pharmacokinetics

Absorption
After a dose of conventional (instant-release) oral oxycodone, the onset of action is 10–30 minutes,[5][4] and peak plasma levels of
the drug are attained within roughly 30–60 minutes;[5][4][43] in contrast, after a dose of OxyContin (an oral controlled-release
formulation), peak plasma levels of oxycodone occur in about three hours.[25] The duration of instant-release oxycodone is 3 to 6
[4]
hours, although this can be variable depending on the individual.

Distribution
Oxycodone in the blood is distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain.[25] Conventional oral
preparations start to reduce pain within 10–15 minutes on an empty stomach; in contrast, OxyContin starts to reduce pain within one
hour.[16]

Metabolism
The metabolism of oxycodone in humans is extensive (about 95%) and complex, with many minor pathways and resulting
metabolites.[4][44] Around 10% (range 8–14%) of a dose of oxycodone is excreted essentially unchanged (unconjugated or
conjugated) in the urine.[4] The major metabolites of oxycodone are noroxycodone (70%), noroxymorphone ("relatively high
concentrations"),[23] and oxymorphone (5%).[43][45] The immediate metabolism of oxycodone in humans is as follows:
[4][7][46]

N-demethylation to noroxycodone predominantly via CYP3A4

O-demethylation to oxymorphone predominantly via CYP2D6
6-ketoreduction to 6α- and 6β-oxycodol
N-oxidation to oxycodone-N-oxide
In humans, N-demethylation of oxycodone to noroxycodone by CYP3A4 is the major metabolic pathway, accounting for 45% ± 21%
of a dose of oxycodone, while O-demethylation of oxycodone into oxymorphone by CYP2D6 and 6-ketoreduction of oxycodone into
6-oxycodols represent relatively minor metabolic pathways, accounting for 11% ± 6% and 8% ± 6% of a dose of oxycodone,
respectively.[4][35]

Several of the immediatemetabolites of oxycodone are subsequently conjugated withglucuronic acid and excreted in the urine.[4] 6α-
Oxycodol and 6β-oxycodol are further metabolized by N-demethylation to nor-6α-oxycodol and nor-6β-oxycodol, respectively, and
by N-oxidation to 6α-oxycodol-N-oxide and 6β-oxycodol-N-oxide (which can subsequently be glucuronidated as well),
respectivelyrespectively.[4][7] Oxymorphone is also further metabolized, as follows:
[4][7][46]

3-glucuronidation to oxymorphone-3-glucuronidepredominantly via UGT2B7

6-ketoreduction to 6α-oxymorphol and 6β-oxymorphol
N-demethylation to noroxymorphone
The first pathway of the above three accounts for 40% of the metabolism of oxymorphone, making oxymorphone-3-glucuronidethe
main metabolite of oxymorphone, while the latter two pathways account for less than 10% of the metabolism of oxymorphone.[46]
After N-demethylation of oxymorphone,noroxymorphone is further glucuronidated tonoroxymorphone-3-glucuronide.[46]

Activity contribution of metabolites

A few of the metabolites of oxycodone have also been found to be active as MOR agonists, some of which notably have much higher
affinity for (as well as higher efficacy at) the MOR in comparison.[43][47][48] Oxymorphone possesses 3- to 5-fold higher affinity for
the MOR than does oxycodone,[4] while noroxycodone and noroxymorphone possess one-third of and 3-fold higher affinity for the
MOR, respectively,[4][48] and MOR activation is 5- to 10-fold less with noroxycodone but 2-fold higher with noroxymorphone
relative to oxycodone.[45] Noroxycodone, noroxymorphone, and oxymorphone also have longerhalf-lives than oxycodone.[43][49]

Ki ([3H]diprenorphine EC50 (hMOR1 GTPyS Cmax (20 mg AUC (20 mg

Compound[23][45] CR)
displacement) binding) CR)

23.2 ± 236 ±
Oxycodone 16.0 nM 343 nM
8.6 ng/mL 102 ng/h/mL
0.82 ± 12.3 ±
Oxymorphone 0.36 nM 42.8 nM
0.85 ng/mL 12 ng/h/mL
15.2 ± 233 ±
Noroxycodone 57.1 nM 1930 nM
4.5 ng/mL 102 ng/h/mL
Noroxymorphone 5.69 nM 167 nM ? ?

However, despite the greater in vitro activity of some of its metabolites, it has been determined that oxycodone itself is responsible
for 83.0% and 94.8% of its analgesic effect following oral and intravenous administration, respectively.[47] Oxymorphone plays only
a minor role, being responsible for 15.8% and 4.5% of the analgesic effect of oxycodone after oral and intravenous administration,
respectively.[47] Although the CYP2D6 genotype and the route of administration result in differential rates of oxymorphone
formation, the unchanged parent compound remains the major contributor to the overall analgesic effect of oxycodone.[47] In contrast
to oxycodone and oxymorphone, noroxycodone and noroxymorphone, while also potent MOR agonists, poorly cross the blood-brain-
barrier into the central nervous system, and for this reason, are only minimally analgesic in comparison.[43][45][47][48] In accordance,
while higher CYP2D6 activity increases the effects of oxycodone (owing to increased conversion into oxymorphone), higher
CYP3A4 activity has the opposite effect, and decreases the effects of oxycodone (owing to increased metabolism into noroxycodone
and noroxymorphone).[50]

Variation
Oxycodone is metabolized by the cytochrome P450 enzyme system in the liver, making it vulnerable to drug interactions.[25] Some
people are fast metabolizers, resulting in reduced analgesic effect, but increased adverse effects, while others are slow metabolisers,
resulting in increased toxicity without improved analgesia.[51][52] The dose of oxycodone must be reduced in patients with reduced
hepatic function.[16]

Elimination
Oxycodone and its metabolites are mainly excreted in the urine and sweat; therefore, it accumulates in patients with kidney
impairment.[16]

Bioavailability
Oxycodone can be administered orally, intranasally, via intravenous, intramuscular, or subcutaneous injection, or rectally. The
bioavailability of oral administration of oxycodone averages 60–87%, with rectal administration yielding the same results; intranasal
varies between individuals with a mean of 46%.[53]

Morphine equivalency
Taken orally, 20 mg of immediate release oxycodone is equivalent to 30 mg of morphine.[54][55] Extended release oxycodone is
considered to be twice as potent as oral morphine.[56]

Chemistry
Oxycodone's chemical name is derived fromcodeine. The chemical structures are very similar, differing only in that

Oxycodone has a hydroxy group at carbon-14 (codeine has just a hydrogen in its place)
Oxycodone has a 7,8-dihydro feature. Codeine has adouble bond between those two carbons; and
Oxycodone has a carbonyl group (as in ketones) in place of the hydroxyl group of codeine.
It is also similar to hydrocodone, differing only in that it has a hydroxyl group at acrbon-14.[16]

Oxycodone is marketed as various salts, most commonly as the hydrochloride salt. The free base conversion ratios of different salts
are: hydrochloride (0.896), bitartrate (0.667), tartrate (0.750), camphosulphonate (0.576), pectinate (0.588), phenylpriopionate
(0.678), sulphate (0.887), phosphate (0.763), and terephthalate (0.792). The hydrochloride salt is the basis of most American
oxycodone products whilst bitartrate, tartrate, pectinate, terephthalate and phosphate salts are also available in European products.
Methyiodide and hydroiodide are mentioned in older European publications.

Biosynthesis
In terms of biosynthesis, oxycodone has been found naturally in nectar extracts from the orchid family Epipactis helleborine;
[57]
together along with another opioid: 3-{2-{3-{3-benzyloxypropyl}-3-indol, 7,8-didehydro- 4,5-epoxy-3,6-d-morphinan.

Detection in biological fluids

Oxycodone and/or its major metabolites may be measured in blood or urine to monitor for clearance, abuse, confirm a diagnosis of
poisoning, or assist in a medicolegal death investigation. Many commercial opiate screening tests cross-react appreciably with
[58]
oxycodone and its metabolites, but chromatographic techniques can easily distinguish oxycodone from other opiates.

History
Freund and Speyer of the University of Frankfurt in Germany first synthesized oxycodone from Thebaine in 1916,[11] a few years
after the German pharmaceutical company Bayer had stopped the mass production of heroin due to hazardous use, harmful use, and
dependence. It was hoped that a thebaine-derived drug would retain the analgesic effects of morphine and heroin with less
dependence. Unfortunately, this was ultimately not found to be the case.
The first clinical use of the drug was documented in 1917, the year after it was first developed.[11][59] It was first introduced to the
US market in May 1939. In early 1928, Merck introduced a combination product containing scopolamine, oxycodone, and ephedrine
under the German initials for the ingredients SEE, which was later renamed Scophedal (SCOpolamine ePHEDrine and eukodAL).
This combination is essentially an oxycodone analogue of the morphine-based ´twilight sleep´, with ephedrine added to reduce
circulatory and respiratory effects.

The personal notes of Adolf Hitler's physician, Dr. Theodor Morell, indicate Hitler received repeated injections of "eukodal"
(oxycodone).[60]

In the early 1970s, the United States government classified oxycodone as a schedule II drug.

Purdue Pharma — a privately held company based in Stamford, Connecticut, developed the prescription painkiller OxyContin. Upon
its release in 1995, OxyContin was hailed as a medical breakthrough, a long-lasting narcotic that could help patients suffering from
moderate to severe pain. The drug became a blockbuster, and has reportedly generated some thirty-five billion dollars in revenue for
Purdue.[61]

Society and culture

Legal status

General
Oxycodone is subject to international conventions on narcotic drugs. In addition, oxycodone is subject to national laws that differ by
country. The 1931 Convention for Limiting the Manufacture and Regulating the Distribution of Narcotic Drugs of the League of
Nations included oxycodone.[62] The 1961 Single Convention on Narcotic Drugs of the United Nations, which replaced the 1931
convention, categorized oxycodone in Schedule I.[63] Global restrictions on Schedule I drugs include "limit[ing] exclusively to
medical and scientific purposes the production, manufacture, export, import, distribution of, trade in, use and possession of" these
drugs; "requir[ing] medical prescriptions for the supply or dispensation of [these] drugs to individuals"; and "prevent[ing] the
[63]
accumulation" of quantities of these drugs "in excess of those required for the normal conduct of business".

Australia
Oxycodone is in Schedule I (derived from the Single Convention on Narcotic Drugs) of the Commonwealth's Narcotic Drugs Act
1967.[64] In addition, it is in Schedule 8 of the Australian Standard for the Uniform Scheduling of Drugs and Poisons ("Poisons
Standard"), meaning it is a "controlled drug... which should be available for use but require[s] restriction of manufacture, supply,
[65]
distribution, possession and use to reduce abuse, misuse and physical or psychological dependence".

Canada
Oxycodone is a controlled substance under Schedule I of theControlled Drugs and Substances Act(CDSA).[66]

Canadian legislative changes

In February 2012, Ontario passed legislation to allow the expansion of an already existing drug-tracking system for publicly funded
drugs to include those that are privately insured. This database will function to identify and monitor patient’s attempts to seek
prescriptions from multiple doctors or retrieve from multiple pharmacies. Other provinces have proposed similar legislation, while
some, such as Nova Scotia, have legislation already in effect for monitoring prescription drug use. These changes have coincided
with other changes in Ontario’s legislation to target the misuse of painkillers and high addiction rates to drugs such as oxycodone. As
of February 29, 2012, Ontario passed legislation delisting oxycodone from the province’s public drug benefit program. This was a
first for any province to delist a drug based on addictive properties. The new law prohibits prescriptions for OxyNeo except to certain
patients under the Exceptional Access Program including palliative care and in other extenuating circumstances. Patients already
prescribed oxycodone will receive coverage for an additional year for OxyNeo, and after that, it will be disallowed unless designated
under the exceptional access program.[67]

Much of the legislative activity has stemmed from Purdue Pharma’s decision in 2011 to begin a modification of Oxycontin’s
composition to make it more difficult to crush for snorting or injecting. The new formulation, OxyNeo, is intended to be preventative
in this regard and retain its effectiveness as a painkiller. Since introducing its Narcotics Safety and Awareness Act, Ontario has
committed to focusing on drug addiction, particularly in the monitoring and identification of problem opioid prescriptions, as well as
the education of patients, doctors, and pharmacists.[68] This Act, introduced in 2010, commits to the establishment of a unified
database to fulfil this intention.[69] Both the public and medical community have received the legislation positively, though concerns
about the ramifications of legal changes have been expressed. Because laws are largely provincially regulated, many speculate a
[70]
national strategy is needed to prevent smuggling across provincial borders from jurisdictions with looser restrictions.

In 2015, Purdue Pharma's abuse-resistant OxyNEO and six generic versions of OxyContin had been on the Canada-wide approved
list for prescriptions since 2012. In June 2015, then federal Minister of Health Rona Ambrose announced that within three years all
oxycodone products sold in Canada would need to be tamper-resistant. Some experts warned that the generic product manufacturers
[71]
may not have the technology to achieve that goal, possibly giving Purdue Pharma a monopoly on this opiate.

Canadian lawsuits
Several class action suits across Canada have been launched against the Purdue group of companies and affiliates. Claimants argue
the pharmaceutical manufacturers did not meet a standard of care and were negligent in doing so. These lawsuits reference earlier
judgments in the United States, which held that Purdue was liable for wrongful marketing practices and misbranding. Since 2007, the
Purdue companies have paid over CAN$650 million in settling litigation or facing criminal fines.

Germany
The drug is in Appendix III of the Narcotics Act (Betäubungsmittelgesetz or BtMG).[72] The law allows only physicians, dentists,
[72]
and veterinarians to prescribe oxycodone and the federal government to regulate the prescriptions (e.g., by requiring reporting).

Hong Kong
[73]
Oxycodone is regulated under Part I of Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance.

Japan
Oxycodone is a restricted drug in Japan. Its import and export is strictly restricted to specially designated organizations having prior
permit to import it. In a high-profile case an American who was a top Toyota executive living in Tokyo, who claimed to be unaware
[74][75]
of the law, was arrested for importing oxycodone into Japan.

Singapore
Oxycodone is listed as a Class A drug in the Misuse of Drugs Act of Singapore, which means offences in relation to the drug attract
the most severe level of punishment. A conviction for unauthorized manufacture of the drug attracts a minimum sentence of 10 years
of imprisonment and corporal punishment of 5 strokes of the cane, and a maximum sentence of life imprisonment or 30 years of
imprisonment and 15 strokes of the cane.[76] The minimum and maximum penalties for unauthorized trafficking in the drug are
[77]
respectively 5 years of imprisonment and 5 strokes of the cane, and 20 years of imprisonment and 15 strokes of the cane.

United Kingdom
Oxycodone is a Class A drug under the Misuse of Drugs Act.[78] For Class A drugs, which are "considered to be the most likely to
cause harm", possession without a prescription is punishable by up to seven years in prison, an unlimited fine, or both.[79] Dealing of
the drug illegally is punishable by up to life imprisonment, an unlimited fine, or both.[79] In addition, oxycodone is a Schedule 2 drug
per the Misuse of Drugs Regulations 2001 which "provide certain exemptions from the provisions of the Misuse of Drugs Act
1971".[80]

United States
Under the Controlled Substances Act, enacted in 1971 by President Richard Nixon,[81] oxycodone is a Schedule II controlled
substance whether by itself or part of a multi-ingredient medication. The DEA lists oxycodone both for sale and for use in
manufacturing other opioids as ACSCN 9143 and in 2013 approved the following annual aggregate manufacturing quotas: 131.5
.[82]
metric tons for sale, down from 153.75 in 2012, and 10.25 metric tons for conversion, unchanged from the previous year

Recreational use

Effects
Oxycodone, like other opioid analgesics, tends to induce feelings of euphoria, relaxation and reduced anxiety in those who are
occasional users.[83] These effects make it one of the most commonlyabused pharmaceutical drugs in the United States.
[84]

Preventive measures
In August 2010, Purdue Pharma reformulated their long-acting oxycodone line, marketed as OxyContin, using a polymer, Intac,[85]
to make the pills extremely difficult to crush or dissolve[86] in water to reduce OxyContin abuse.[87] The FDA approved relabeling
[88]
the reformulated version as abuse-resistant in April 2013.

Pfizer manufactures a preparation of short-acting oxycodone, marketed as Oxecta, which contains inactive ingredients, referred to as
tamper-resistant Aversion Technology.[89] It does not deter oral abuse. Approved by the FDA in the US in June 2011, the new
[90]
formulation makes crushing, chewing, snorting, or injecting the opioid impractical because of a change in its chemical properties.

Australia
The non-medical use of oxycodone existed from the early 1970s, but by 2015, 91% of a national sample of injecting drug users in
[91]
Australia had reported using oxycodone, and 27% had injected it in the last six months.

Canada
Opioid-related deaths in Ontario had increased by 242% from 1969 to 2014.[92] By 2009 in Ontario there were more deaths from
oxycodone overdose than from cocaine overdose.[93] Deaths from opioid pain relievers had increased from 13.7 deaths per million
[94] The abuse of oxycodone in Canada became a problem. Areas where
residents in 1991 to 27.2 deaths per million residents in 2004.
oxycodone is most problematic are Atlantic Canada and Ontario, where its abuse is prevalent in rural towns, and in many smaller to
medium-sized cities.[95] Oxycodone is also widely available across Western Canada, but methamphetamine and heroin are more
serious problems in the larger cities, while oxycodone is more common in rural towns. Oxycodone is diverted through doctor
shopping, prescription forgery, pharmacy theft, and overprescribing.[95][96]

The recent formulations of oxycodone, particularly Purdue Pharma's crush-, chew-, injection- and dissolve-resistant OxyNEO[97]
which replaced the banned OxyContin product in Canada in early 2012, have led to a decline in the abuse of this opiate but have
increased the abuse of the more potent drug fentanyl.[98] According to a Canadian Centre on Substance Abuse study quoted in
[99]
Maclean's magazine, there were at least 655 fentanyl-related deaths in Canada in a five-year period.
In Alberta, the Blood Tribe police claimed that from the fall of 2014 through January 2015, oxycodone pills or a lethal fake variation
referred to as Oxy 80s[100] containing fentanyl made in illegal labs by members of organized crime were responsible for ten deaths
on the Blood Reserve, which is located southwest of Lethbridge, Alberta.[101] Province-wide, approximately 120 Albertans died
from fentanyl-related overdoses in 2014.[100]

United Kingdom
Abuse and diversion of oxycodone in the UK commenced in the early- to mid-2000s.[102] The first known death due to overdose in
the UK occurred in 2002.[103] However, recreational use remains relatively rare.

United States
In the United States, more than 12 million people use opioid drugs recreationally.[104] In 2010, 16,652 deaths were related to opioid
overdose in combination with other drugs such as benzodiazepines and alcohol.[105] In September 2013, the FDA released new
labeling guidelines for long acting and extended release opioids requiring manufacturers to remove moderate pain as indication for
use, instead stating the drug is for "pain severe enough to require daily, around-the-clock, long term opioid treatment."[106] The
[104]
updated labeling will not restrict physicians from prescribing opioids for moderate, as needed use.

Oxycodone is the most widely recreationally used opioid in America. The U.S. Department of Health and Human Services estimates
that about 11 million people in the US consume oxycodone in a non-medical way annually.[107] In 2007, about 42,800 emergency
room visits occurred due to "episodes" involving oxycodone.[108] Diverted oxycodone may be taken orally or ingested through
insufflation; used intravenously, or the heated vapors inhaled. In 2008, recreational use of oxycodone and hydrocodone were involved
[109]
in 14,800 deaths. Some of the cases were due to overdoses of the acetaminophen component, resulting in fatal liver damage.

Reformulated OxyContin is causing some recreational users to change toheroin, which is cheaper and easier to obtain.[110]

Economics
The International Narcotics Control Board estimated 11.5 short tons (10.4 t) of oxycodone were manufactured worldwide in
1998;[111] by 2007 this figure had grown to 75.2 short tons (68.2 t).[111] United States accounted for 82% of consumption in 2007 at
51.6 short tons (46.8 t). Canada, Germany, Australia, and France combined accounted for 13% of consumption in 2007.[111][112] In
2010, 1.3 short tons (1.2 t) of oxycodone were illegally manufactured using a fake pill imprint. This accounted for 0.8% of
consumption. These illicit tablets were later seized by the U.S. Drug Enforcement Administration, according to the International
Narcotics Control Board.[113] The board also reported 122.5 short tons (111.1 t) manufactured in 2010. This number had decreased
[114]
from a record high of 135.9 short tons (123.3 t) in 2009.

Names
Expanded expression for the compound oxycodone in the academic literature include "dihydrohydroxycodeinone",[2][115][116]
"Eucodal",[115][116] "Eukodal",[1][59] "14-hydroxydihydrocodeinone",[2][115] and "Nucodan".[115][116] In a UNESCO convention,
the translations of "oxycodone" are oxycodon (Dutch), oxycodone (French), oxicodona (Spanish), ‫( اﻷوﻛﺴﻴﻜﻮدون‬Arabic), 羟考酮
(Chinese), and оксикодон (Russian).[117] The word "oxycodone" should not be confused with "oxandrolone", "oxazepam",
"oxybutynin", "oxytocin", or "Roxanol".[118]

Available forms
[5][119][120][121]
Oxycodone is available in a variety of formulations for oral or sublingual administration:

Immediate-release oxycodone (OxyFast, OxyIR, OxyNorm, Roxicodone)

[6]
Controlled-release oxycodone (OxyContin) – 12-hour duration
[122]
Oxycodone tamper-resistant (OxyContin OTR)
Immediate-release oxycodone withparacetamol (acetaminophen) (Percocet, Endocet, Roxicet, T
ylox)
 Immediate -release oxycodone withaspirin (Endodan, Oxycodan, Percodan, Roxiprin)
Immediate-release oxycodone withibuprofen (Combunox)[123]
Controlled-release oxycodone withnaloxone (Targin, Targiniq, Targinact)[124] – 12-hour duration
Controlled-release oxycodone withnaltrexone (Troxyca) – 12-hour duration –pending regulatory approval[125]
Europe.[35][31][126]
Parenteral formulations of oxycodone (brand name OxyNorm) are also available, and are widely used in

See also
Equianalgesic List of deaths from drug overdose and intoxication
Froehde reagent Psychoactive drug
Illegal drug trade

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Further reading
 Coluzzi, F. & Mattia, C. (July–August 2005)."Oxycodone. Pharmacological profile and clinical data in chronic pain
management" (PDF). Minerva Anestesiol. 71 (7–8): 451–60. PMID 16012419. Archived from the original (PDF) on
March 9, 2006.

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