Oxycodone
 |
 |
| Systematic (IUPAC) name |
| (5R,9R,13S,14S)-4,5α-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one |
| Clinical data |
| Trade names |
Oxycodone |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a682132 |
| Pregnancy cat. |
B/D (prolonged use or in high doses at term) |
| Legal status |
Controlled (S8) (AU) Schedule I (CA) ? (UK) Schedule II (US) |
| Dependence liability |
Moderate–High |
| Routes |
oral, intramuscular, intravenous, intranasal, subcutaneous, transdermal, rectal, epidural[1] |
| Pharmacokinetic data |
| Bioavailability |
100% (IV); Up to 87% (oral)[2] |
| Protein binding |
45% |
| Metabolism |
Hepatic: primarily CYP3A, secondarily CYP2D6[3] |
| Half-life |
3–4.5 hr |
| Excretion |
Urine (19% unchanged) |
| Identifiers |
| CAS number |
76-42-6  Y |
| ATC code |
N02AA05
N02AA55 (in combinations) |
| PubChem |
CID 5284603 |
| DrugBank |
DB00497 |
| ChemSpider |
4447649 Y |
| UNII |
CD35PMG570 Y |
| KEGG |
D05312 Y |
| ChEBI |
CHEBI:7852 Y |
| ChEMBL |
CHEMBL656 Y |
| Synonyms |
dihydrohydroxycodeinone, 14-hydroxydihydrocodeinone, 6-deoxy-7,8-dihydro-14-hydroxy-3-O-methyl-6-oxomorphine[4] |
| Chemical data |
| Formula |
C18H21NO4 |
| Mol. mass |
315.364 g/mol |
| SMILES |
eMolecules & PubChem |
-
InChI=1S/C18H21NO4/c1-19-8-7-17-14-10-3-4-12(22-2)15(14)23-16(17)11(20)5-6-18(17,21)13(19)9-10/h3-4,13,16,21H,5-9H2,1-2H3/t13-,16+,17+,18-/m1/s1 Y
Key:BRUQQQPBMZOVGD-XFKAJCMBSA-N Y
|
| Physical data |
| Solubility in water |
HCl: 166 mg/mL (20 °C) |
 Y (what is this?) (verify)
|
Oxycodone is an analgesic medication synthesized from poppy-derived thebaine. It was developed in 1916 in Germany,[5][6] as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine (heroin), and codeine.[1]
Oxycodone oral medications are generally prescribed for the relief of moderate to severe pain. Currently it is formulated as single ingredient products or compounded products. Some common examples of compounding are oxycodone with acetaminophen/paracetamol or NSAIDs such as ibuprofen. The formulations are available as generics but are also made under various brand names. OxyContin is Purdue Pharma's brand for time-release oral oxycodone. The manufacturing rights to time-released generic oxycodone are under dispute.
Oxycodone is effective for managing moderate to moderately severe acute or chronic pain.[7] It has been found to improve quality of life for those with many types of pain.[8]
Oxycodone can also be used as a alternative to other opiates to treat severe diarrhea and diarrhea predominant irritable bowel syndrome when drugs such as loperamide and diphenoxylate are ineffective.
In 2001 the European Association for Palliative Care recommended that oral oxycodone be a second-line alternative to oral morphine for cancer pain.[9] There is no evidence that any opioids are superior to morphine in relieving the pain of cancer, and no controlled trials have shown oxycodone to be superior to morphine.[10] However, compared to morphine, oxycodone causes less respiratory depression, sedation, pruritus, and nausea. As a result, it is generally better tolerated than morphine.
The most commonly reported effects include memory loss, constipation, fatigue, dizziness, nausea, lightheadedness, headache, dry mouth, anxiety, itching, and heavy sweating.[12] It has also been claimed to cause dimness in vision due to miosis. Some patients have also experienced loss of appetite, nervousness, abdominal pain, diarrhea, urine retention, dyspnea, and hiccups,[2] although these symptoms appear in less than 5% of patients taking oxycodone. Rarely, the drug can cause impotence, enlarged prostate gland, and decreased testosterone secretion.
In high doses, overdoses, or in patients not tolerant to opiates, oxycodone can cause shallow breathing, bradycardia, cold, clammy skin, apnea, hypotension, miosis (pupil constriction), circulatory collapse, respiratory arrest, and death.[2]
There is a high risk of experiencing severe withdrawal symptoms if a patient discontinues oxycodone abruptly. Therefore therapy should be discontinued gradually rather than abruptly. People who use oxycodone in a hazardous or harmful fashion are at even higher risk of severe withdrawal symptoms as they tend to use higher than prescribed doses. The symptoms of oxycodone withdrawal are the same as for other opiate based painkillers and may include "anxiety, panic attack, nausea, insomnia, muscle pain, muscle weakness, fevers, liver damage,[13]]and other flu like symptoms".[14]
Withdrawal symptoms have also been reported in newborns whose mothers had been either injecting or orally taking oxycodone during pregnancy.[15]
Oxycodone and/or its major metabolites may be quantitated in blood or urine to monitor for abuse, confirm a diagnosis of poisoning or assist in a medicolegal death investigation. Many commercial opiate screening tests cross-react appreciably with oxycodone and its metabolites, but chromatographic techniques can easily distinguish oxycodone from other opiates.[16]
A group of Australian researchers has proposed (based on a 1997 study in rats) that oxycodone, unlike morphine (the effect of which is mediated by μ-opioid receptors), acts on κ-opioid receptors.[17] Further research by this group indicates the drug appears to be a κ2b-opioid agonist.[18] However, this has been disputed, primarily on the basis that oxycodone produces effects typical of μ-opioid agonists.[19]
Research by a Japanese group suggests that 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,[20] while in non-diabetic mice the μ1-opioid receptor seems to be primarily responsible for these effects.[21]
After a dose of conventional oral oxycodone, peak plasma levels of the drug are attained in approximately one hour;[3] in contrast, after a dose of OxyContin (an oral continuous release formulation), peak plasma levels of oxycodone occur in about three hours.[2]
Oxycodone in the blood is distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain.[2] Conventional oral preparations of oxycodone start to reduce pain within 10–15 minutes; in contrast, OxyContin starts to reduce pain within 1 hour.[7]
Oxycodone is metabolized to α and β oxycodol; oxymorphone, then α and β oxymorphol and noroxymorphone; and noroxycodone, then α and β noroxycodol and noroxymorphone (N-desmethyloxycodone).[3] (14-Hydroxydihydrocodeine that in turn becomes 14-Hydroxydihydromorphine) These metabolites are true only for humans.[22] As many as six metabolites for oxycodone (14-hydroxydihydromorphinone, 14-hydroxydihydrocodeine, 14-hydroxydihydrocodeinone N-oxide {oxycodone N-oxide}, 14-hydroxydihydroisocodeine, 14-hydroxydihydrocodeine N-oxide, and noroxycodone) have been found in rabbits,[23] several of which are thought to be active metabolites to some extent, although a study using conventional oral oxycodone concluded that oxycodone itself, and not its metabolites, is predominantly responsible for the drug's opioid effects on the brain.[3]
Oxycodone is metabolized by the cytochrome P450 enzyme system in the liver, making it vulnerable to drug interactions.[2] 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.[24][25] The dose of OxyContin must be reduced in patients with reduced hepatic function.[7]
Oxycodone and its metabolites are mainly excreted in the urine and sweat; therefore, it accumulates in patients with renal impairment.[7]
Oxycodone can be administered orally, intranasally, via intravenous/intramuscular/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%.[26]
Oxycodone is approximately 1.5–2 times as potent as morphine when administered orally.[27][28] However, 10–15 mg of oxycodone produces an analgesic effect similar to 10 mg of morphine when administered intramuscularly.[29] Therefore, as a parenteral dose, morphine is approximately up to 50% more potent than oxycodone.
There are no comparative trials showing that oxycodone is more effective than any other opioid. In palliative care, morphine remains the gold standard;[10] however, oxycodone can be useful as an alternative opioid if a patient has troublesome adverse effects with morphine.
Oxycodone's chemical name is derived from codeine. The chemical structures are very similar, differing only in that
- Oxycodone has a hydroxyl group at carbon-14 (codeine has just a hydrogen in its place), hence oxycodone;
- Oxycodone has a 7,8-dihydro feature, whereas codeine has a double bond between those two carbons; and
- Oxycodone has a carbonyl group (as in ketones) in place of the hydroxyl group of codeine, hence the "-one" suffix.
It is also similar to hydrocodone, differing only in that it has a hydroxyl group at carbon-14.[7]
Expanded expression for the compound oxycodone in the academic literature include "dihydrohydroxycodeinone",[4][30][31] "Eucodal",[30][31] "Eukodal",[1][32] "14-hydroxydihydrocodeinone",[4][30] and "Nucodan".[30][31] In a UNESCO convention, the translations of "oxycodone" are oxycodon (Dutch), oxycodone (French), oxicodona (Spanish), الأوكسيكودون (Arabic), 羟考酮 (Chinese), and оксикодон (Russian).[33] The word "oxycodone" should not be confused with "oxandrolone", "oxazepam", "oxybutynin", "oxytocin", or "Roxanol".[34]
Freund and Speyer of the University of Frankfurt in Germany first synthesized oxycodone from thebaine in 1916,[6] 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. To some extent this was achieved, as oxycodone does not have the same immediate effect as heroin or morphine nor does it last as long.
The first clinical use of the drug was documented in 1917, the year after it was first developed.[6][32] 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 & eukodAL)—this combination is essentially an oxycodone analogue of the morphine-based Twilight Sleep with ephedrine added to reduce circulatory and respiratory effects.
The International Narcotics Control Board estimates that 11.5 tons (23,000 lbs) of oxycodone were manufactured worldwide in 1998;[35] by 2007 this figure had grown to 75.2 tons (150,400 lbs).[35] Of all countries, the United States had the highest total consumption of oxycodone in 2007 at 51.6 tons (103,200 lbs) or 82% of the world total. This translates into over half a billion 80 mg tablets per year.[35] In addition, the U.S. had the highest per capita consumption of oxycodone, followed by Canada in 2006, 2007 and 2008. This makes the consumption of oxycodone in North America (United States and Canada alone) higher than all other countries of the world combined. The United States and Canada are consistently ranked among the top two or three in most type of opioid consumption per capita (for example, in 2006 Canada ranked second and the U.S. ranked third in morphine consumption per capita; only Austria ranked higher and that is due to the fact that in addition to being used to treat moderate to severe pain, morphine is also used to treat heroin or morphine dependence in Austria—a practice which is unheard of in North America).[35][36]
All brand-names not marked otherwise are standard-release tablets or capsules of oxycodone without further pharmacologically active ingredients.
- Dinarkon (Germany)
- Diphydrone
- Endocet (US) (compounded with paracetamol)—by Endo
- Endodan (US) (compounded with acetylsalicylic acid)—by Endo
- ETH-Oxydose (US)
- Endone (US)—by Endo
- Eukodal (Germany) (for injection)
- OxyContin (US) (modified release)—by Purdue Frederick
- Oxycocet (Canada) compounded with acetaminophen-by ratiopharm inc.
- OxyFast (US) (oral liquid)
- OxyNEO (Canada) (slow release HCl reformulation)
- OxyNorm (UK/US) (tablets, oral liquid, liquid for injection)
- OxyNormoro (France)—by Mundipharma
- Pancodine
- Percodan (US) (compounded with acetylsalicylic acid)—by Endo
- Percodan-Demi (US) (compounded with acetylsalicylic acid)—by Endo
- Percocet (US) (compounded with paracetamol)—by Endo
- Percolone (US)—by Endo
- Roxicet (US)—by Roxane
- Roxicodone (US)—by Roxane
- Roxilox (US)—by Roxane
- Roxiprin (US) (compounded with acetylsalicylic acid)—by Roxane
- Supeudol (Canada)—by Sandoz
- Thekodin (Germany)
- Tylox (US)
OxyContin is the brand name of a time-release formula of oxycodone produced by the pharmaceutical company Purdue Pharma.[37] It was approved by the U.S. Food and Drug Administration in 1995 and first introduced to the U.S. market in 1996.[37] By 2001, OxyContin was the best-selling non-generic narcotic pain reliever in the U.S.; 2008 sales in the U.S. totaled $2.5 billion.[38] An analysis of data from the U.S. Drug Enforcement Administration found that retail sales of oxycodone "jumped nearly six-fold between 1997 and 2005".[39] Mundipharma distributes OxyContin in Australia,[40] China,[41] and Europe.[42]
In 2001, Purdue Pharma permanently suspended distribution of 160 mg tablets in the U.S. because of the "possibility of illicit use of tablets of such high strength". It is speculated that the DEA had requested Purdue to discontinue manufacturing the 160 mg Tablets; however, the DEA has publicly denied asking Purdue to do so.[37][43] Beginning in 2010, the brand name OxyContin by Purdue was reformulated to prevent the misuse and abuse of the tablets. Additional binders have been added to prevent the grinding of tablets for insufflation or injection, and to maintain OxyContin's extended release characteristics.[44] These new tablets are more often prescribed by physicians than previous generic versions for this exact purpose and bear the stamp 'OP' instead of the previous 'OC.'
Purdue has multiple patents for OxyContin, but has been involved in a series of ongoing legal battles on the validity of these patents. On June 7, 2005, the United States Court of Appeals for the Federal Circuit upheld a decision from the previous year that some of Purdue’s patents for OxyContin could not be enforced.[45] This decision allowed and led to the immediate announcement from Endo Pharmaceuticals that would begin launching a generic version of all four strengths of OxyContin.[46] Purdue, however, had already made negotiations with another pharmaceutical company (IVAX Pharmaceuticals) to distribute their brand OxyContin in a generic form.[46] This contract was severed, and as of October 2005 Watson Pharmaceuticals became the exclusive U.S. distributor of Purdue-manufactured generic versions of OxyContin tablets in 10-, 20-, 40-, and 80-milligram dosages.[47]
On February 1, 2006, the Federal Circuit Court of Appeals issued a decision revising its 2005 decision.[48] This time the court vacated the lower court's "judgment that the patents-in-suit are unenforceable due to inequitable conduct", and the case was "remanded for further proceedings".[48]
Purdue Pharma has since announced resolution of its infringement suits with Endo,[49] Teva,[50] IMPAX,[51] and Mallinckrodt.[52] Endo and Teva each agreed to cease selling generic forms of OxyContin.[49][50] IMPAX negotiated a temporary, and potentially renewable, license.[51] In 2008, Mallinckrodt Pharmaceuticals reintroduced generic OxyContin in the strengths of 10 mg, 20 mg, 40 mg and 80 mg, which was made possible by a temporary royalties-bearing license with Purdue Pharma that expired in 2009.[52]
Critics have accused Purdue Pharma of putting profits ahead of public interest by applying "significant political pressure" to attempt to reverse South Carolina's requiring prior approval before a person with Medicaid can receive the drug;[53] for "fail[ing] to adequately warn consumers of the risks" of OxyContin such as dependence;[54] and for promoting the drug "aggressively" and by means such as "promotional beach hats, pedometers and swing-music CDs".[54][55]
In May 2007 Purdue Pharma "agreed to pay $19.5 million" in fines relating to aggressive off-label marketing practices of OxyContin in 26 states and the District of Columbia.[56] In specific, the company encouraged dosing more frequent than the recommended interval of 12 hours, and did not fully disclose the risk of hazardous or harmful use.[56]
Later in May 2007 Purdue Pharma and three of its top executives pled guilty in a Virginia federal court to charges that they misbranded OxyContin by representing it to have "less euphoric effect and less abuse potential" than it actually has, and by claiming that people taking the drug at low doses could stop taking it suddenly without symptoms of withdrawal.[57] The FDA had not approved these claims.[58] The company and the executives were to pay $634 million in fines for felony and misdemeanor misbranding.[57]
In October 2007, officials in Kentucky filed a lawsuit against Purdue Pharma for misleading health care providers and consumers "regarding the appropriate uses, risks and safety of OxyContin"; as of mid-2008, however, the case had been "consolidated with other lawsuits into a single multi-litigation suit" in a federal court in New York.[59]
There are conflicting arguments in Canada regarding the representation of OxyContin in the media and academic publications. Across the country, national and local newspapers and television news broadcasts, often highlight the potential side effects and outcomes of the drug.[60] Media reports have also criticized Purdue Pharma, the company responsible for the oxycodone brand, for promoting the drug with the promise to provide individuals a prolonged relief from pain, with minimal side effects.[61] Although the addictive properties of OxyContin are no more than other opioids, the health risks are heightened through its aggressive marketing practices.[62][61] Advertisements in professional publications and medical journals have been consistent, touting the drug “as a safer alternative to even Aspirin and Tylenol and good for anyone who needed pain relief for ‘several days’ or more.”[62][63] Advertisements in Monthly Prescribing Reference reiterate these claims by emphasizing OxyContin’s flexibility in regards to its dosage strength.[63] In addition to the zealous advertisements, the National Post revealed in 2011 that the company promoted the brand through “a textbook, website and presentations by paid experts that encouraged more liberal prescribing of opioids, based on debatable evidence.” [62][61]
Despite these criticisms however, Health Canada and the Pharmaceutical Advertising Advisory Board (a non-governmental organization) claim that they have not received any complaints or concerns regarding Purdue’s promotions for OxyContin.[62] In addition, the Canadian Pain Society has accused media representations of OxyContin as being misleading and one-sided. The organization points out that the coverage often ignores the vast group of individuals who use the drug responsibly and benefit from its effects, focusing instead on a small group of individuals who use the drug recklessly.[64]
This notion is echoed in the research paper entitled Representations of OxyContin in North American Newspapers and Journals. In the paper, Whelan et al. (2011) state that since the branding of OxyContin as ‘hillbilly heroin’ and a street drug, the drug has consistently been depicted as a social problem across Atlantic Canada, and other impoverished, rural areas in North America. Referring to 27 North American newspapers (6 Canadian) and 33 medical journals (with a focus on addiction, substance abuse, pain, and general medicine), the objective of the research was to examine and compare the coverage of OxyContin and show how each medium contributes to the social problems related to the opiod. Using statistical analysis, the results revealed that newspaper reports highlighted the controversies associated with the drug, concentrating on stories regarding the abuse, crimes, and death rather than its beneficial uses for treating pain. In addition, Whelan et al. (2011) discovered inconsistencies in the physicians reports in newspaper and medical journals, particularly those in fields of pain medicine and addiction medicine. Through this, the authors concluded that the “prevalence of negative representations of OxyContin is often blamed on biased media coverage and an ignorant public. However, the proliferation of inconsistent messages regarding the drugs from physicians plays a role in the drug’s persistent status as a social problem.”[60]
Xanodyne pharmaceutical 30mg Roxicodone immediate release tablet
Oxy·IR immediate-release oxycodone tablets from Purdue Pharma in Canada are available in 5, 10, and 20 mg strengths.[65] Effective August 10, 2009, Purdue discontinued manufacture and distribution of OxyIR Capsules.
OxyNorm is available in 5, 10, and 20 mg capsules, and also as a 5 mg/5 ml liquid in 250 ml bottles in Australia, New Zealand, the Netherlands and the UK.[66][67][68] In addition, OxyNorm is available in a 10 mg/ml liquid concentrate for oral use in the Netherlands and the UK, and in 10 mg/ml solutions and 50 mg/ml solutions for injection or infusion in New Zealand, the Netherlands and the UK.[68][69] It is also available in Australia as Endone, a generic 5 mg tablet.
Percocet (oxycodone with paracetamol/acetaminophen) tablets are available in Canada and the U.S. with 2.5, 5, 7.5, and 10 mg of oxycodone and varying amounts of acetaminophen.[70]
Depalgos (oxycodone with paracetamol) tablets are marketed in Italy, with 325 mg Paracetamol and 5, 10, and 20 mg oxycodone. Recent legislation in Italy has made it easier for physicians to prescribe this medication and other opioids to pain patients.[71]
Percodan tablets available in the U.S. contain 4.8355 mg of oxycodone HCl and 325 mg of aspirin.[72]
Proladone suppositories, available in Australia, contain 30 mg of oxycodone pectinate.[73]
Roxicodone, a generic oxycodone product designed to have an immediate release effect, is available in 5 mg (white), 15 mg (green), and 30 mg (blue) tablets; in a 5 mg per 5 ml oral solution; and in a 20 mg per ml liquid concentrate.[74][75] On March 31, 2009, the U.S. Food and Drug Administration directed Boehringer Ingelheim Roxane and Xanodyne Pharmaceuticals to cease manufacture and distribution of 5 mg Roxicodone tablets in the U.S. because they lacked proper approval.[76] In the US Oxycodone Immediate Release tablets are also available in 10 mg (pink) and 20 mg (grey) tablets from KVK-Tech, a generic manufacturer. Targin is a tablet with a prolonged-release oxycodone/naloxone combination.
In the US, oxycodone was initially produced by Endo Pharmaceuticals in 1950 as the prescription drug Percodan, a formulation of 5 mg oxycodone and 325 mg aspirin. Percodan, and later formulations of oxycodone which also included non-narcotic painkillers, were problematic drugs of abuse, but the dosage of oxycodone one could use was limited by the other ingredients in the pill, which also primarily restricted the routes of administration to oral ingestion. It wasn't until 1995, however, that oxycodone abuse skyrocketed after the FDA approval of Oxycontin by Purdue Pharma. Oxycontin is a formulation of nearly pure oxycodone available in up to 80 mg in one pill, developed to provide 12 hours of time-release pain relief. Abusers quickly learned that you could crush the pill to release pure oxycodone, which allowed larger doses and by additional routes of administrations such as intravenous and intranasal. In 2011, however, Purdue pharmaceuticals updated their formulation to include an abuse-resistant polymer that has decreased the recreational value of Oxycontin, since the time release cannot be broken easily. Since then, Roxane Laboratories and their 15 mg and 30 mg instant release oxycodone formulation, has quickly become the new formulation of choice by abusers. These pills are known by their street names: Roxies, Blues, Berries, and "30s". There are many generic equivalents available of 10 mg, 15 mg, 20 mg, and 30 mg instant release oxycodone formulations. Abusers commonly ingest, insufflate, smoke or intravenously inject the drug.
Mallinckrodt brand 30mg Generic.
The illegal use of OxyContin began in Australia in the early 2000s. By 2007, 51% of a national sample of injection drug users in Australia had reported using oxycodone, and 27% had injected it in the last six months.[77]
File:Oxycocet.jpg
Oxycodone 5 mg with acetaminophen (paracetamol) 325 mg formulation by TevaCanada pharmaceuticals; generic form of Percocet.
Deaths from opioid pain relievers increased from 13.7 deaths per million residents in 1991 to 27.2 deaths per million residents in 2004, which may be related to the spread of OxyContin.[78] After the United States, Canada was the world's largest per capita consumer of oxycodone in 2006, 2007, and 2008. The per capita consumption of oxycodone in Canada and the U.S. together is higher than all other countries of the world combined.[35][36] The abuse of oxycodone in Canada, particularly the OxyContin formulation, has become a very severe problem. Areas where oxycodone is most problematic are Atlantic Canada and Ontario, where its abuse is rampant in rural towns and in many smaller to medium sized cities it has become more readily available than heroin.[79] Although abuse of the drug is seen among all age groups, oxycodone is more rampant in the suburbs and among those under the age of 30, while heroin remains the main opioid of abuse among those over the age of 30, the homeless, and among those that reside in the inner city where street gangs control the distribution of heroin. However, despite the obvious problems with opioids of all kinds, cocaine, especially crack cocaine, remains the biggest drug threat.[80][81] 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 over-prescribing.[79][82]
Hazardous use, harmful use and diversion of OxyContin in the UK commenced in the early- to mid-2000s.[83] The first known death due to OxyContin overdose in the UK occurred in 2002.[84]
The United States was the world's largest consumer of oxycodone per capita in 2006, 2007, and 2008.[35][36] Instances of recreational use and diversion of OxyContin have increased in the U.S. beginning in the late 1990s.[85] The slang term hillbilly heroin (which originally referred to hydromorphone) for OxyContin refers to the occurrence of the "earliest reported cases of Oxycontin abuse" in the U.S. in rural areas such as Appalachia.[86] Diversion of OxyContin in the U.S. may occur through "fraudulent prescriptions, doctor shopping, over-prescribing, and pharmacy theft".[85]
A 2003 study by the Government Accountability Office found three factors that may have contributed to the illicit use and distribution of OxyContin in the U.S.:[37]
- OxyContin contains a large amount of oxycodone compared with other types of oxycodone containing pills.
- OxyContin's warning label said to not crush the controlled-release tablets because of the potential for rapid release of oxycodone, which led to many people crushing the tablets and injecting or snorting the drug.
- By 2001, sales of OxyContin in the U.S. exceeded $1 billion per year.
A study published in 2005 examined the prevalence of opiate analgesic use among "recreational drug users and street addicts" as perceived by "key informants" throughout the U.S.; the authors found that non-clinical use of opiates was increasing in general, but that of the drugs studied use of OxyContin "was mentioned most frequently".[87] Purdue Pharma has attempted to reformulate the 10–40 mg strengths of OxyContin to prevent the release of a high percentage of the oxycodone by crushing; however, in 2008 a joint panel convened by the U.S. Food and Drug Administration was "concerned that abusers could find a way to manipulate the new formulation".[88] In 2010, Purdue Pharma introduced 'Oxycontin OP', Purdue Pharma predicts that abuse of higher dose formulations such as 'OxyContin' will go down, but this change may cause heavy recreational users to resort to other drugs such as heroin or may increase the number of deaths caused by acetaminophen poisoning from users attempting to take similar doses of drugs like 'Percocet' or 'Vicodin' to get similar effects. Since 'Oxycontin OP' has now fully saturated the street markets, recreational users find it nearly impossible to find the original Oxycontin formulations.
One investigation in Boston found that OxyContin was a "gateway" drug for heroin, which addicts turned to as a cheaper alternative.[89]
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.[90] The 1961 Single Convention on Narcotic Drugs of the United Nations, which replaced the 1931 convention, categorized oxycodone in Schedule I.[91] 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 accumulation" of quantities of these drugs "in excess of those required for the normal conduct of business".[91]
Oxycodone is in Schedule I (derived from the Single Convention on Narcotic Drugs) of the Commonwealth's Narcotic Drugs Act 1967.[92] In addition, it is in Schedule 8 of the Australian Standard for the Uniform Scheduling of Drugs and Poisons ("Poisons Standard"), meaning that it is a "controlled drug... which should be available for use but require[s] restriction of manufacture, supply, distribution, possession and use to reduce abuse, misuse and physical or psychological dependence".[93]
Oxycodone is a controlled substance under Schedule I of the Controlled Drugs and Substances Act (CDSA).[94] Every person who seeks or obtains from a practitioner either the substance or an authorization to obtain the substance must disclose to that practitioner information on all controlled substances and authorizations for controlled substances obtained from any other practitioner within the preceding 30 days; otherwise, the person may be found "guilty of an indictable offence and liable to imprisonment for a term not exceeding seven years".[94] Anyone possessing the substance for the purpose of trafficking "is guilty of an indictable offence and liable to imprisonment for life".[94] While the drug remains a controlled substance, after March 1 2012, it will be removed from pharmacy shelves and replaced with OxyNEO, which producer Purdue Pharma declares is more difficult to abuse and misuse.[95]
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 will be disallowed unless designated under the exceptional access program.[96] Saskatchewan has recently joined Atlantic Canada in its efforts to curb abuse of OxyContin by also pulling public funding for the drug.[97] Much of the legislative activity has stemmed from drug manufacturer Purdue Pharma’s decision in 2011 to begin a modification of Oxycodone’s composition making it more difficult to crush for snorting or injecting. The new formulation known as OxyNeo, is intended to be preventative in this regard and retain its effectiveness as a pain killer. 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.[98] This Act, introduced in 2010, commits to the establishment of a unified database to fulfill this intention.[99] 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 that a national strategy is needed to prevent smuggling across provincial borders from jurisdictions with looser restrictions.[100]
Several class action suits across Canada have been launched against the Purdue group of companies and affiliates. Claimants argue that 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 650 million dollars in settling litigation or facing criminal fines.[101]
The drug is in Appendix III of the Narcotics Act ("Betäubungsmittelgesetz" or BtMG).[102] The law states that only physicians, dentists and veterinarians ("Ärzte, Zahnärzte und Tierärzte") can prescribe oxycodone, and that the federal government can regulate the prescriptions (e.g., by requiring reporting).[102]
Oxycodone is regulated under Part I of Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance.[103] The penalty for trafficking (Section 4) or manufacturing (Section 6) the substance is a $5,000,000 HKD fine and/or life imprisonment.[103] In Section 8 of the Ordinance, possession of the substance for consumption without licence from the Department of Health is illegal and subject to a $1,000,000 HKD fine and/or 7 years of imprisonment.[103] Per Sections 22–23, only specific health professionals and others (e.g., "a person in charge of a laboratory used for the purposes of research") may possess and supply the substance.[103] Anyone who supplies the substance without a valid prescription can be fined $10,000 HKD according to Section 31.[103]
Oxycodone is listed as a Class A drug in the Misuse of Drugs Act of Singapore, which means that 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 ten years' imprisonment and corporal punishment of five strokes of the cane, and a maximum sentence of life imprisonment or 30 years' imprisonment and 15 strokes of the cane.[104] The minimum and maximum penalties for unauthorized trafficking in the drug are respectively five years' imprisonment and five strokes of the cane, and 20 years' imprisonment and 15 strokes of the cane.[105]
Oxycodone is a Class A drug under the Misuse of Drugs Act.[106] 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.[107] Dealing of the drug illegally is punishable by up to life imprisonment, an unlimited fine, or both.[107] 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".[108]
Under the Controlled Substances Act, oxycodone is a Schedule II controlled substance because it "has a high potential for abuse", because it "has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions", and because use of the drug "may lead to severe psychological or physical dependence".[109] According to Section 829 of the Act, Schedule II drugs must be dispensed only with the written prescription of a practitioner except in certain situations (e.g., "dispensed directly by a practitioner, other than a pharmacist", or "dispensed upon oral prescription (i.e. telephone)" in "emergency situations only").[109] Furthermore, Section 829 specifies that prescriptions for Schedule II drugs cannot be refilled.[109]
As of April 2010 an "abuse resistant", controlled release formulation of Oxycontin was approved for sale in the United States. The reformulated OxyContin is intended to lessen the ability to tamper with the opioid medication — from being cut, broken, chewed, crushed or dissolved, however, there is no evidence that the reformulation of OxyContin is less subject to misuse, abuse, diversion, overdose, or addiction.[110] The abuse resistant formulation is recognizable by a pill marking "OP" on one side and the milligrams of oxycodone contained within the pill on the other. The previous formulation has an "OC" marking replacing the "OP" of the new formulation.[111]
This article uses the terms "hazardous use", "harmful use", and "dependence" in accordance with
Lexicon of alcohol and drug terms published by the
World Health Organization (WHO) in 1994.
[112] In WHO usage, the first two terms replace the term "abuse" and the third term replaces the term "addiction".
[112]
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- ^ OxyContin Canada: Saskatchewan Joins Atlantic Provinces And Ontario In Pulling Funding. Huffington Post. Canadian Press. (2012-02-22)
- ^ Narcotics Safety and Awareness Act. 2010. Ministry of Health and Long Term Care.
- ^ Irfan Dhalla, Irfan & Born, Karen. Health Debate. (2012-02-22)
- ^ Ontario OxyContin Rules: New Restrictions Applauded But National Rules Needed. Huffington Post. Canadian Press (2012-02-20)
- ^ Martin, Kevin. Lawsuit attacks OxyContin use. C-Health. Sun Media (2008-08-08)
- ^ a b German Federal Ministry of Justice (2009-01-19). "Act on the circulation of narcotics (Narcotics Act – BtMG)" (in German). http://bundesrecht.juris.de/btmg_1981/BJNR106810981.html. Retrieved 2009-04-06.
- ^ a b c d e Hong Kong Special Administrative Region, People's Republic of China. "Dangerous drugs ordinance – chapter 134". Hong Kong Legal Information Institute. http://www.hklii.org/hk/legis/en/ord/cur/134.txt. Retrieved 2009-04-08.
- ^ Misuse of Drugs Act (Cap. 185, 2008 Rev. Ed.) (Singapore), section 6(1).
- ^ Misuse of Drugs Act (Singapore), section 5(1).
- ^ "List of drugs currently controlled under the Misuse of Drugs legislation". UK. Home Office. 2009. http://www.homeoffice.gov.uk/documents/cdlist.pdf?view=Binary. Retrieved 2009-04-08.
- ^ a b "Class A, B and C drugs". UK. Home Office. http://www.homeoffice.gov.uk/drugs/drugs-law/Class-a-b-c/. Retrieved 2009-04-08.
- ^ "Statutory instrument 2001 No. 3998. The Misuse of Drugs regulations 2001". UK. Office of Public Sector Information. http://www.opsi.gov.uk/si/si2001/20013998.htm. Retrieved 2009-04-08.
- ^ a b c "(United States Code.) Title 21 – food and drugs. Chapter 13 – drug abuse prevention and control". U.S. Drug Enforcement Administration. http://uscode.house.gov/download/pls/21C13.txt. Retrieved 2011-07-23.
- ^ Letter from Purdue Pharma L.P. to Healthcare Professional, October 4, 2010
- ^ ""FDA Approves New Formulation of OxyContin Designed to reduce abuse of the prescription painkiller, though it has failed to stop the addiction epidemic. People are still finding ways to abuse the substance, or just turns to heroin to keep themselves from going into withdrawals.", consumeraffairs.com (April 6, 2010)". Consumeraffairs.com. 2010-04-06. http://www.consumeraffairs.com/news04/2010/04/oxycontin_fda.html. Retrieved 2010-08-01.
- ^ a b Babor T (1994) (PDF). Lexicon of alcohol and drug terms. Geneva: World Health Organization. ISBN 92-4-154468-6. http://whqlibdoc.who.int/publications/9241544686.pdf.
- Meier, Barry (2003). Pain killer: a "wonder" drug's trail of addiction and death. Emmaus, PA: Rodale. ISBN 1-57954-638-2.
- Pinsky, Drew (2004). When painkillers become dangerous: what everyone needs to know about OxyContin and other prescription drugs. Center City, MN: Hazelden. ISBN 1-59285-107-X.
- Lockwood, Brad (2006). Oxycontin: from pain relief to addiction. New York: Rosen Pub. Group, Inc. ISBN 978-1-4042-0913-8.
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Opioids
See also: Opioids template |
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Opium & alkaloids thereof
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Semi-synthetic opium
derivatives
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Synthetic opioids
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| Pyrazolones |
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| Cannabinoids |
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| Anilides |
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Non-steroidal
anti-inflammatories
See also: NSAIDs template |
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Propionic acid class
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Oxicam class
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Acetic acid class
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Anthranilic acid
(fenamate) class
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Atypical, adjuvant and potentiators,
metabolic agents and miscellaneous |
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| Major recreational drugs |
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| Drug culture |
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| Problems with drug use |
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| Legality of drug use |
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International
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State level
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Drug policy
by country
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Other
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| Lists of countries by... |
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