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{{Short description|Opioid analgesic drug}}
{{Lead too long|date=April 2010}}
{{Distinguish|Oxymorphazone}}
{{Citations missing|date=December 2010}}
{{Use dmy dates|date=August 2024}}
{{Drugbox
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 408787245
| class = [[Opioid]]
| IUPAC_name = 4,5α-epoxy-3,14-dihydroxy-<br />17-methylmorphinan-6-one
| verifiedrevid = 456483627
| image =Oxymorphone 2D structure.svg
| drug_name =
<!--Clinical data-->
| type =
| tradename = Opana
| IUPAC_name = 4,5α-Epoxy-3,14-dihydroxy-17-methylmorphinan-6-one
| Drugs.com = {{drugs.com|monograph|oxymorphone-hydrochloride}}
| image = Oxymorphone.png
| MedlinePlus = a610022
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| width = 170px
| pregnancy_US = C
| alt =
| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
| caption =
| image2 = Oxymorphone3DanJ.gif
| legal_CA = Schedule I
| width2 = 250px
| legal_UK = Class A
| legal_US = Schedule II
| dependency_liability = High
| routes_of_administration = intravenous, intramusucular, subcutaneous, oral, rectal, insufflation.


<!-- Clinical data -->| tradename = Numorphan, Numorphone, Opana, others
<!--Pharmacokinetic data-->
| Drugs.com = {{drugs.com|monograph|oxymorphone-hydrochloride}}
| bioavailability = 10% (oral) 40% (Intranasal) 100% (IV, IM)
| MedlinePlus = a610022
| metabolism = hepatic
| licence_EU =
| elimination_half-life = 1.3 +/- 0.7 hrs (with parenteral admin)<ref>[http://www.rxlist.com/cgi/generic/oxymorphone_cp.htm rxlist.com]</ref>; 7.25-9.43 hr (with oral admin)<ref>{{cite journal | author = Adams MP, Ahdieh H | title = Single- and multiple-dose pharmacokinetic and dose-proportionality study of oxymorphone immediate-release tablets | journal = Drugs R D | year = 2005 | pages = 91–9 | volume = 6 | issue = 2 | pmid = 15777102 | doi = 10.2165/00126839-200506020-00004}}</ref>
| DailyMedID = Oxymorphone
| excretion = 35% urine, 65% feces
| pregnancy_AU =
| pregnancy_category =
| addiction_liability = High
| routes_of_administration = [[Oral administration|By mouth]], [[Buccal administration|buccal]], [[sublingual]], [[intranasal]], [[intravenous]], [[epidural]], [[Subcutaneous injection|subcutaneous]], [[intramuscular]]
| ATC_prefix = N02
| ATC_suffix = AA11
| legal_AU = S8
| legal_BR = A1
| legal_BR_comment =<ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 – Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 – Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023}}</ref>
| legal_CA = Schedule I
| legal_UK = Class A
| legal_US = [[Controlled Substances Act#Schedule II controlled substances|Schedule II]]<ref>{{cite web|title=Drugs@FDA: FDA Approved Drug Products|url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm|website=www.accessdata.fda.gov|access-date=7 November 2017}}</ref>
| legal_DE = Anlage II
| legal_status = <!-- Pharmacokinetic data -->
| dependency_liability = High
| bioavailability = by mouth: 10%<br /> Buccal: 28%<br /> Sublingual: 37.5%<br /> Intranasal: 43%<ref>{{cite journal | vauthors = Hussain MA, Aungst BJ | title = Intranasal absorption of oxymorphone | journal = Journal of Pharmaceutical Sciences | volume = 86 | issue = 8 | pages = 975–6 | date = August 1997 | pmid = 9269879 | doi = 10.1021/js960513x }}</ref><br />IV, IM & IT: 100%<ref name="OUP09">{{cite book | isbn = 978-0-19-157532-7 | title = Opioids in Cancer Pain | vauthors = Davis MP, Glare PA, Hardy J | edition = 2nd | year = 2009 | orig-year = 2005 | publisher = Oxford University Press | location = Oxford, UK | pages = Chapter 17|url=https://books.google.com/books?id=aEzg6i2nPMQC&q=978-0-19-157532-7 }}</ref>
| protein_bound = 10%<ref name = OUP09/>
| metabolism = [[Liver]] ([[CYP3A4]], [[glucuronidation]])<ref name = OUP09/>
| metabolites = • [[Noroxymorphone]]<br> • glucuronide
| elimination_half-life = 10–12 hours<ref name="FiresteinBudd2016">{{cite book| vauthors= Polsten GR, Wallace MS | chapter = Analgesic Agents in Rheumatic Disease | veditors = Firestein GS, Budd R, Gabriel SE, McInnes IB, O'Dell JR |title=Kelley and Firestein's Textbook of Rheumatology | chapter-url = https://books.google.com/books?id=kBZ6DAAAQBAJ&pg=PA1081 |date=21 June 2016|publisher=Elsevier Health Sciences|isbn=978-0-323-41494-4|pages=1081–}}</ref>
| duration_of_action = Duration of action: 6–8 hours orally,
4–6 hrs parenteral
| excretion = Urine, feces<ref name = OUP09/>


<!--Identifiers-->
<!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 76-41-5
| CASNo_Ref = {{cascite|correct|CAS}}
| PubChem = 5284604
| CAS_number = 76-41-5
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ATC_prefix = N02
| ChEMBL = 963
| ATC_suffix = A
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| PubChem = 5284604
| ChemSpiderID = 4447650
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01192
| DrugBank = DB01192
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| IUPHAR_ligand = 7094
| ChemSpiderID = 4447650
| UNII_Ref = {{fdacite|correct|FDA}}
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08323
| UNII = 9VXA968E0C
| KEGG_Ref = {{keggcite|correct|kegg}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9VXA968E0C
| KEGG = D08323
| synonyms = 14-Hydroxydihydromorphinone
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 963


<!--Chemical data-->
<!-- Chemical data -->| C = 17
| C=17 | H=19 | N=1 | O=4
| H = 19
| N = 1
| molecular_weight = 301.33706 g/mol
| O = 4
| smiles = CN1CC[C@]23c4c5ccc(c4O[C@H]2C(=O)CC[C@]3([C@H]1C5)O)O
| SMILES = CN1CC[C@]23c4c5ccc(O)c4O[C@H]2C(=O)CC[C@@]3(O)[C@H]1C5
| InChI = 1/C17H19NO4/c1-18-7-6-16-13-9-2-3-10(19)14(13)22-15(16)11(20)4-5-17(16,21)12(18)8-9/h2-3,12,15,19,21H,4-8H2,1H3/t12-,15+,16+,17-/m1/s1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| InChIKey = UQCNKQCJZOAFTQ-ISWURRPUBQ
| StdInChI = 1S/C17H19NO4/c1-18-7-6-16-13-9-2-3-10(19)14(13)22-15(16)11(20)4-5-17(16,21)12(18)8-9/h2-3,12,15,19,21H,4-8H2,1H3/t12-,15+,16+,17-/m1/s1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C17H19NO4/c1-18-7-6-16-13-9-2-3-10(19)14(13)22-15(16)11(20)4-5-17(16,21)12(18)8-9/h2-3,12,15,19,21H,4-8H2,1H3/t12-,15+,16+,17-/m1/s1
| StdInChIKey = UQCNKQCJZOAFTQ-ISWURRPUSA-N
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = UQCNKQCJZOAFTQ-ISWURRPUSA-N
| synonyms = 14-Hydroxydihydromorphinone
}}
}}
<!-- Definition and medical uses -->
'''Oxymorphone''' ('''Opana''', '''Numorphan''', '''Numorphone''') or 14-Hydroxydihydro[[morphinone]] is a powerful semi-synthetic [[opioid]] [[analgesic]] first developed in Germany circa 1914, patented in the USA by [[Endo Pharmaceuticals]] in 1955<ref>{{ cite patent
| country = US
| number = 2806033
| status = patent
| title = MORPHINE DERIVATIVE
| pubdate = 1955-03-08
| gdate = 1957-10-09
| inventor = Mozes Juda Leweustein
}}</ref> and introduced to the United States market in January 1959 and other countries around the same time. It (along with hydromorphone) was designed to have less incidence of side effects than morphine and heroin. It was a success as it differs from morphine and heroin in its effects in that it generates less euphoria, sedation, itching and other histamine effects at equianalgesic doses. This also means a lower dependence liability.


'''Oxymorphone''' (sold under the brand names '''Numorphan''' and '''Opana''' among others) is a highly potent [[opioid]] [[analgesic]] indicated for treatment of severe pain. Pain relief after injection begins after about 5–10 minutes, after oral administration it begins after about 30 minutes, and lasts about 3–4 hours for immediate-release tablets and 12 hours for extended-release tablets.<ref>{{cite journal | vauthors = Sloan P | title = Review of oral oxymorphone in the management of pain | journal = Therapeutics and Clinical Risk Management | volume = 4 | issue = 4 | pages = 777–87 | date = August 2008 | pmid = 19209260 | pmc = 2621383 | doi = 10.2147/tcrm.s1784 | doi-access = free }}</ref> The elimination half-life of oxymorphone is much faster intravenously, and as such, the drug is most commonly used orally.<ref>{{cite journal| vauthors = Smith HS |date=1 April 2009|title=Clinical Pharmacology of Oxymorphone|journal=Pain Medicine|language=en|volume=10|issue=suppl_1|pages=S3–S10|doi=10.1111/j.1526-4637.2009.00594.x|issn=1526-2375|doi-access=free}}</ref> Like [[oxycodone]], which metabolizes to oxymorphone, oxymorphone has a high potential to be abused.<ref>{{cite journal | vauthors = Babalonis S, Lofwall MR, Nuzzo PA, Walsh SL | title = Pharmacodynamic effects of oral oxymorphone: abuse liability, analgesic profile and direct physiologic effects in humans | journal = Addiction Biology | volume = 21 | issue = 1 | pages = 146–58 | date = January 2016 | pmid = 25130052 | pmc = 4383736 | doi = 10.1111/adb.12173 }}</ref>
The brand name Numorphan is derived by analogy to the Nucodan name for an [[oxycodone]] product (or vice versa) as well as Paramorphan/Paramorfan for [[dihydromorphine]] and Paracodin ([[dihydrocodeine]]). The only commercially available salt of oxymorphone in most of the world at this time is the hydrochloride, which has a free base conversion ratio of 0.891.


<!-- Society and culture -->
In some countries, [[hydromorphinol]] is distributed under the trade names Numorphan and Numorphan Oral. This is a relatively rare exception and the two drugs, whilst both being strong opioid analgesics, are notably different from one another.
It was developed in Germany in 1914. It was patented in 1955 and approved for medical use in 1959.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=52X |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA52X |language=en}}</ref> In June 2017 the [[FDA]] asked [[Endo Pharmaceuticals]] to remove its product from the US market.<ref>{{cite journal| vauthors = Wolf LK |date=19 June 2017|title=FDA takes aim at opioid epidemic|url=https://cen.acs.org/articles/95/i25/FDA-takes-aim-at-opioid-epidemic.html|journal=[[Chemical & Engineering News]]|volume=95|issue=25|pages=8}}</ref> This was in part due to the [[opioid epidemic]] in the US, and the fact that a 2012 reformulation failed to stop illicit injection of the drug. Endo responded by voluntarily removing Opana ER from the market a month later.<ref>{{cite web | author = Office of the Commissioner |title=Press Announcements – FDA requests removal of Opana ER for risks related to abuse|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm562401.htm|website=www.fda.gov|language=en|date=10 September 2019}}</ref> Generic versions of extended-release oxymorphone, such as those manufactured by [[Amneal Pharmaceuticals]], are still available in the US.<ref>{{cite news| vauthors = Bernstein L, Merle R |url=https://www.washingtonpost.com/health/six-drug-companies-subpoenaed-in-federal-opioids-probe/2019/11/27/745899e6-112e-11ea-bf62-eadd5d11f559_story.html|title=Six drug companies subpoenaed in federal opioids probe|date=27 November 2019|newspaper=[[The Washington Post]]|access-date=18 April 2020}}</ref>


==Medical uses==
Oxymorphone is administered as its [[hydrochloride|hydrochloride salt]] via injection, or [[suppository]]; typically in dosages of 1&nbsp;mg (injected) to 5&nbsp;mg (suppository). Endo has been the major distributor of oxymorphone throughout the world and currently markets oxymorphone in the United States and elsewhere as '''Opana''' and '''Opana ER'''.
Oxymorphone Immediate Release is indicated for the relief of moderate to severe pain, such as treatment of acute post surgical pain.<ref>{{cite journal | vauthors = Sloan P | title = Review of oral oxymorphone in the management of pain | journal = Therapeutics and Clinical Risk Management | volume = 4 | issue = 4 | pages = 777–87 | date = August 2008 | pmid = 19209260 | pmc = 2621383 | doi = 10.2147/TCRM.S1784 | doi-access = free }}</ref> For any chronic treatment of pain, clinicians should only consider long term use if there is significant clinical benefit to the patient's therapy that outweigh any potential risk. The first line treatment choices for chronic pain are non-pharmacological and non-opioid agents.<ref>{{cite web |title=Guideline for Prescribing Opioids for Chronic Pain |url=https://www.cdc.gov/drugoverdose/pdf/guidelines_factsheet-a.pdf |website=CDC |access-date=2 November 2018}}</ref>


Oxymorphone extended-release tablets are indicated for the management of chronic pain and only for people already on a regular schedule of strong opioids for a prolonged period. Immediate-release oxymorphone tablets are recommended for breakthrough pain for people on the extended-release version. Compared to other opioids, oxymorphone has similar pain relieving efficacy.<ref>{{cite web |title=Cancer pain management with opioids: Optimizing analgesia |url=https://www.uptodate.com/contents/cancer-pain-management-with-opioids-optimizing-analgesia?search=opana&source=search_result&selectedTitle=2~75&usage_type=default&display_rank=1#H12 |website=UpToDate }}</ref>
Opana is available as 5&nbsp;mg and 10&nbsp;mg tablets; Opana ER, an extended-release form of oxymorphone, is available as tablets in strengths of 5&nbsp;mg,10&nbsp;mg, 20&nbsp;mg, 30&nbsp;mg, and 40&nbsp;mg. The 7½ mg and 15 mg strengths of Opana ER have been discontinued as of March 1, 2011<ref>http://www.fda.gov/downloads/Drugs/DrugSafety/DrugShortages/UCM245101.pdf</ref>. Some resources assert that 2, 12 and/or 15&nbsp;mg IR tablets and 25, 36 and 50&nbsp;mg extended release tablets will be introduced although apparently the timeline on that is not known to the public at this time. Opana Extended-Release tablets are based on the TIMERx system developed by a consortium led by Endo and [[Penwest]]. Some of these strengths (notably not the 7.5&nbsp;mg) are available in an Opana IR–immediate release–form for [[Pain#Breakthrough_pain|breakthrough pain]] to be used by patients already on 24/7 opioid care such as [[fentanyl]] patches and sustained-relief morphine drugs like Avinza.


In the United States it is a Schedule II controlled substance with an [[ACSCN]] of 9652.<ref>{{cite web |title=Administration Controlled Substance Code Number |url=https://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_03.htm |website=Drug Enforcement Administration US |publisher=DEA |access-date=2 November 2018 |archive-date=17 October 2018 |archive-url=https://web.archive.org/web/20181017100709/https://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_03.htm |url-status=dead }}</ref>
In addition to the sustained-release version for Opana, other versions of TIMERx are available and being developed for other protocols such as increasing, decreasing, stepwise increasing, and stepwise decreasing dose delivery over time, single and multiple bursts of medication, and combinations of the above.


Oxymorphone ER Tablets should be taken on an empty stomach.<ref>{{Cite web|title=Oxymorphone ER Tablet|url=https://my.clevelandclinic.org/health/drugs/18265-oxymorphone-er-tablet|website=ClevelandClinic.org}}</ref>
Specifically, the apparent extension of the duration of effect of the IR tablets (all other things being equal, oxymorphone has a duration of action of 5 to 8 hours in most patients) versus similar drugs in commonly used immediate-release forms—for example [[Dilaudid]] ([[hydromorphone]]), [[morphine]], Vilan([[nicomorphine]]), Paramorfan ([[dihydromorphine]]) as well as [[prodrugs]] for this group such as [[hydrocodone]], [[nicocodeine]], [[codeine]], [[dihydrocodeine]] and others—is often attributed to a marginal extended-release effect from various excipients, particularly those that are hydrophilic and form a gel-like substance at the pH levels in the stomach and duodenum.


==Availability==
Both as the result of this and the pharmacokinetics of oxymorphone, the IR tablets have a de facto duration of action of 5 to 13 hours (the mean would seem to be around 7 hours with a moderately small standard deviation and a left-skewed and [[leptokurtic]] frequency distribution) in patients with normal kidney and liver function. As a result, patients rotated on to extended release oxymorphone preparations from other opioids may very well need the Opana IR tablets, Numorphan ampoules or phials with hypodermic needles and/or a PCA pump, or immediate-release formulations of [[hydromorphone]], [[dihydromorphine]], high dose [[oxycodone]], [[hydromorphinol]], [[nicomorphine]], [[diamorphine]], or [[morphine]] for breakthrough pain incidents already in progress. An oxymorphone nasal spray is reportedly in development, along with a possible hydromorphone nasal spray and implantable osmotic pumps for both drugs.


=== Brands and forms ===
The duration of action and metabolic half-life of oxymorphone mean that immediate-release tablets are more similar to analgesic preparations of [[methadone]], [[levorphanol]], [[piritramide]], and existing extended-release forms of morphine, oxycodone, [[ketobemidone]] and so on. The extended-release Opana tablets can provide detectable analgesia for anywhere from 6 to 36+ hours (the mean appears to be very close to the lower end of the continuum), largely contingent on things that can alter the drug's liberation, absorption, distribution, metabolism, and elimination profile. One cause is unusual conditions in the upper and middle GI tract, such as created by [[misoprostol]] and Arthrotec (misoprostol plus [[diclofenac]]). Among other things, misoprostol is a smooth muscle agent with both a contact and systemic mucousagogue that coats the stomach and adjacent areas with increasing amounts of mucus. This can result in everything from even slower onset of action to intact tablets being passed with stool.
Oxymorphone was marketed by Endo Pharmaceuticals, under the brand name(s) Opana and Opana ER. Opana ER was withdrawn by the manufacturer in 2017 due to a [[FDA]] request, making it unavailable in the US.<ref>{{cite web | title = Endo to Pull Opana From the Market Following FDA Request. | work = Pharmacy Times. | vauthors = Barrett J | date = 6 July 2017 | url = https://www.pharmacytimes.com/product-news/endo-to-pull-opana-from-the-market-following-fda-request | access-date = 1 November 2018 | archive-date = 20 November 2018 | archive-url = https://web.archive.org/web/20181120095706/https://www.pharmacytimes.com/product-news/endo-to-pull-opana-from-the-market-following-fda-request | url-status = dead }}</ref> However, both IR (immediate release) and ER (extended release) formulations are still available under the generic name Oxymorphone and Oxymorphone ER, provided by a multitude of different manufacturers.


Oxymorphone is also available as an injectable for inpatient use, available for IV ([[Intravenous therapy|intravenous]]), IM ([[Intramuscular injection|intramuscular]]), and SC ([[Subcutaneous injection|subcutaneous]]) injection.
Oxymorphone is also produced within the human body when the liver metabolises [[oxycodone]] by means of O demethylation catalysed by the [[CYP2D6]] enzyme. Approximately 10% of the dose is processed by the endocrine system in this respect; this can vary widely from person to person. The [[codeine]]-[[hydrocodone]] group and [[morphinan]]s exhibit the same characteristics.


An extended release (ER) [[Modified-release dosage|modified-release dosage form]] is commonly used, which modifies the [[pharmacokinetics]] of the drug.
Consuming alcohol with Opana extended-release tablets can be an extremely dangerous situation. The absorption of oxymorphone can vary wildly in the presence of alcohol. Plasma concentrations were found to be as low as -50% of expected to as much as 270% more than expected. Elevated plasma levels could result in overdose. Opana ER does not cause "[[dose dumping]]," which creates a blast of drug release that plagues other long acting opioids.


== Uses ==
=== Oral dosage forms ===
Oxymorphone comes in a variety of doses.
Oxymorphone is indicated for the relief of moderate to severe pain and also as a preoperative medication to alleviate apprehension, maintain anesthesia, and as an obstetric analgesic. Additionally, it can be used for the alleviation of pain in patients with dyspnea associated with acute left ventricular failure and pulmonary oedema.
{| class="wikitable"
|-
! IR Tablet<ref name = "Oxymorphone_Insert">{{cite web | title = Oxymorphone IR Package Insert | work = Endo Pharmaceuticals | publisher = U.S. Food and Drug Administration | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021611s007lbl.pdf | access-date = 19 November 2018 }}</ref>!! ER 12 Hour Tablet<ref name = "Oxymorphone_Insert" />
|-
| 5&nbsp;mg || 5&nbsp;mg
|-
| 10&nbsp;mg || 7.5&nbsp;mg
|-
| || 10&nbsp;mg
|-
| || 15&nbsp;mg
|-
| || 20&nbsp;mg
|-
| || 30&nbsp;mg
|-
| || 40&nbsp;mg
|}


== Special populations ==
Opana extended-release tablets are indicated for the management of chronic pain of all or most aetiologies and are indicated only for patients already on a regular schedule of strong opioids for a prolonged period. The immediate-release Opana tablets are recommended for management of breakthrough pain for patients on the extended-release version. Some protocols for chronic pain conditions characterised by severe breakthrough pain incidents add Numorphan ampoules as a third form of the drug for use when a breakthrough pain incident is in progress. An oxymorphone nasal spray is being developed for this purpose but the release date is unknown; some practitioners prefer [[fentanyl]] immediate-release formulations such as [[Actiq]] or [[Fentora]] for this purpose although some patients have severe side effects from fentanyl.
Patients already suffering from debilitation are at a much higher risk of respiratory depression. Nonopioid analgesics should be considered in this population.


Elderly patients are much more sensitive to adverse effects, such as falls, cognitive impairment and constipation, and should be monitored for such. Decreased renal function associated with aging leads to decreased clearance of the drug, resulting in narrow therapeutic windows and increasing the danger of overdose. If oxymorphone is absolutely indicated, smaller initial doses should be started for this population.
Oxymorphone is used in veterinary medicine in many of the same uses as for humans, with induction and maintenance of anaesthetia and sometimes tranquillisation of small and medium-sized animals being the most common use. [[Morphine]], [[hydromorphone]], various [[fentanyl]]s, [[levorphanol]], and [[butorphanol]] are also common in veterinary settings and [[tramadol]] is reportedly being studied as a general analgesic for cats, dogs, ferrets, rats and other animals in that size range.


There is a risk of neonatal withdrawal symptom in the newborn if pregnant women take oxymorphone for a prolonged period. Oxymorphone crosses the placenta and holds risk of birth defects, poor fetal growth, stillbirth, and preterm delivery. The children of mothers who are physically dependent on oxymorphone have a higher risk of similar dependence. Due to these severe risks, oxymorphone is highly discouraged among this population. The amount of transfer of oxymorphone into the breast milk is not known and women are cautioned to weigh the risks and benefits before breastfeeding while on this medication.<ref>{{cite web|url=http://www.crlonline.com/lco/action/doc/retrieve/docid/patch_f/7423#pri|title=Login|website=www.crlonline.com|language=en-US|access-date=1 November 2018}}</ref>
Oxymorphone is mentioned,along with buprenorphine, oxycodone, dihydrocodeine, morphine and other opioids as a possible means of mitigating refractory depression.<ref name="pmid10588427">{{cite journal
|author=Stoll AL, Rueter S
|title=Treatment augmentation with opiates in severe and refractory major depression
|journal=Am J Psychiatry
|volume=156
|issue=12
|pages=2017
|pmid=10588427
|url=http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=10588427
|accessdate=2009-03-03
|date= December 1, 1999 }}</ref><ref name="pmid15744636">{{cite journal
|author=Schürks M, Overlack M, Bonnet U
|title=Naltrexone treatment of combined alcohol and opioid dependence: deterioration of co-morbid major depression
|journal=Pharmacopoeia
|volume=38
|issue=2
|pages=100–2
|year=2005
|month=March
|pmid=15744636
|doi=10.1055/s-2005-837812
}}</ref><ref name="pmid7501657">{{cite journal
|author=Tejedor-Real P, Mico JA, Maldonado R, Roques BP, Gibert-Rahola J
|title=Implication of endogenous opioid system in the learned helplessness model of depression
|journal=Pharmacol Biochem Behav
|volume=52
|issue=1
|pages=145–52
|year=1995
|month=September
|pmid=7501657
|doi=10.1016/0091-3057(95)00067-7
}}</ref> Opioids were commonly used for this indication up until the introduction of the tricyclic antidepressants in the 1950s, even though the latter appear to work in a smaller percentage of cases and are generally more toxic than most chemical classes of opioids. Conversely, tricyclic anti-depressants and chemically-related drugs are the most commonly-used adjuvants and atypical analgesics used with opioids for pain, especially neuropathic pain.


==Side effects==
== Physical characteristics ==
The principal adverse effects of oxymorphone are similar to other opioids with constipation, nausea, vomiting, dizziness, dry mouth and drowsiness being the most common adverse effects. This drug is highly addictive as with other opioids and can lead to chemical dependence and withdrawal.<ref name = MD>{{cite web|title=Oxymorphone Hydrochloride|work=Martindale: The Complete Drug Reference|publisher=Pharmaceutical Press|date=30 January 2013|access-date=5 May 2014|url=http://www.medicinescomplete.com/mc/martindale/current/6249-a.htm| veditors = Brayfield A }}</ref>
Oxymorphone HCl occurs as odorless white crystals or white to off-white powder. It darkens in color with prolonged exposure to light, though this does not affect potency. One gram of oxymorphone is soluble in 4 ml of water, and it is slightly soluble in alcohol and ether. The commercially available injection has a pH of 2.7–4.5.


== Toxicity ==
==Overdose==
In common with other opioids, oxymorphone overdosage is characterized by respiratory depression, extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes [[bradycardia]] and [[hypotension]]. In a severe case of overdose, [[apnea]], [[circulatory collapse]], [[cardiac arrest]], and death may occur.
In common with other opioids, oxymorphone overdosage is characterized by respiratory depression, sleepiness progressing to stupor or coma, skeletal muscle [[flaccidity|weakness]], cold and clammy skin, and sometimes [[bradycardia|slow heart rate]] and [[hypotension|low blood pressure]]. In a severe case of overdose, [[apnea]], [[circulatory collapse]], cardiac arrest and death can occur.<ref name = MD/>


==Pharmacology==
At equianalgesic doses oxymorphone is marginally more toxic than morphine but less so than fully synthetic opioids such as methadone and pethidine{{Citation needed|date=April 2011}}. At therapeutic doses, toxicity is primarily manifested as miosis, nausea, and possibly occasional mild involuntary muscle movements especially in the distal portions of the extremities and the shoulder area in some cases. This is most common in patients taking a number of other drugs for their condition, especially muscle relaxants and some adjuvant analgesics, and also appears to happen most often during and immediately after a significant upward titration in the single-dose and per 24 hour doses.


===Pharmacodynamics===
Instances of the body suddenly jerking bolt upright from a more relaxed sitting position is a sign of high and/or rapidly increasing serum levels of opioids and all of the above movements are likely due to the anticholinergic or anticholinergic-like effects of opioids and/or other medications prescribed at the same time, as they manifest in patients on atropine-like drugs as well. The primary risk here involves dropping objects, spilling liquids, striking body parts against walls, and potentially losing footing on flat ice surfaces.
Oxymorphone elicits its effects by binding to and activating the [[μ-opioid receptor]] (MOR) and, to a much lesser extent, the [[δ-opioid receptor]] (DOR) and [[κ-opioid receptor]] (KOR).<ref name = OUP09/> Its activity at the DOR may augment its action at the MOR.<ref name = OUP09/> Oxymorphone is 10 times more potent than morphine.<ref name="pmid16317569">{{cite journal | vauthors = Prommer E | title = Oxymorphone: a review | journal = Supportive Care in Cancer | volume = 14 | issue = 2 | pages = 109–115 | date = February 2006 | pmid = 16317569 | doi = 10.1007/s00520-005-0917-1 | s2cid = 26359576 }}</ref> The calculation of relative potency indicated that 1 mg of oxymorphone hydrochloride equaled 9.85 mg of morphine sulfate, or 1.02 mg of oxymorphone hydrochloride was equivalent to 10 mg of morphine sulfate.<ref>{{cite journal | vauthors = Eddy NB, Lee LE | title = The analgesic equivalence to morphine and relative side action liability of oxymorphone (14-hydroxydihydro morphinone) | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 125 | issue = 2 | pages = 116–121 | date = February 1959 | pmid = 13631610 | url = https://pubmed.ncbi.nlm.nih.gov/13631610/ | access-date = 14 July 2021 }}</ref>


{| class="wikitable <!--floatright-->" style="text-align: center;"
While all this can be frightening at first, more than 85 percent of patients do not experience it at any time during treatment, and oxymorphone does not appear to induce seizures in neurologically healthy patients as does the pethidine series of opioids (pethidine, anileridine, alphaprodine, piminodine and others) nor does it have toxic metabolites that accumulate in the system as do pethdine synthetic opioids. There is also no real evidence that oxymorphone significantly lowers the seizure threshold like tramadol and some of the other synthetics mentioned above.
|+ Oxymorphone at opioid receptors<ref name="CorbettPaterson1993">{{cite book | vauthors = Corbett AD, Paterson SJ, Kosterlitz HW |chapter=Selectivity of Ligands for Opioid Receptors|volume=104 / 1|year=1993|pages=645–679|issn=0171-2004|doi=10.1007/978-3-642-77460-7_26|title=Opioids|series=Handbook of Experimental Pharmacology|isbn=978-3-642-77462-1}}</ref>
|-
! colspan="3" | [[Binding affinity|Affinities]] ({{abbrlink|K<sub>i</sub>|Inhibitor constant}}) || Ratio
|-
! {{abbrlink|MOR|μ-Opioid receptor}} !! {{abbrlink|DOR|δ-Opioid receptor}} !! {{abbrlink|KOR|κ-Opioid receptor}} !! MOR:DOR:KOR
|-
| 0.78&nbsp;nM || 50&nbsp;nM || 137&nbsp;nM || 1:64:176
|}


{| class="wikitable"
== Brand Names ==
|+ Equianalgesic doses<ref name="King2010">{{cite book | vauthors = King TL, Miller EL | chapter = Analgesia and Anesthesia | veditors = King TL, Brucker MC |title=Pharmacology for Women's Health|chapter-url=https://books.google.com/books?id=o_rHHCsIpckC&pg=PA332|date=25 October 2010|publisher=Jones & Bartlett Publishers|isbn=978-1-4496-1073-9|pages=332–}}</ref><ref name="ChestnutWong2014">{{cite book| vauthors = Chestnut DH, Wong CA, Tsen LC, Ngan Kee WD, Beilin Y, Mhyre J |title=Chestnut's Obstetric Anesthesia: Principles and Practice E-Book|url=https://books.google.com/books?id=FMU0AwAAQBAJ&pg=PA611|date=28 February 2014|publisher=Elsevier Health Sciences|isbn=978-0-323-11374-8|pages=611–}}</ref><ref name="Tiziani2013">{{cite book| vauthors = Tiziani AP |title=Havard's Nursing Guide to Drugs|url=https://books.google.com/books?id=XpzQAgAAQBAJ&pg=PA933|date=1 June 2013|publisher=Elsevier Health Sciences|isbn=978-0-7295-8162-2|pages=933–}}</ref>
* Numorphan (suppository and injectable solution)
|-
* Opana ER (extended-release tablet)
! Compound !! [[Route of administration|Route]] !! [[Dose (biochemistry)|Dose]]
* Opana IR (immediate-release tablet)
|-
| [[Codeine]] || {{abbr|PO|Oral administration}} || 200&nbsp;mg
|-
| [[Hydrocodone]] || {{abbr|PO|Oral administration}} || 20–30&nbsp;mg
|-
| [[Hydromorphone]] || {{abbr|PO|Oral administration}} || 7.5&nbsp;mg
|-
| [[Hydromorphone]] || {{abbr|IV|Intravenous administration}} || 1.5&nbsp;mg
|-
| [[Morphine]] || {{abbr|PO|Oral administration}} || 30&nbsp;mg
|-
| [[Oxycodone]] || {{abbr|IV|Intravenous administration}} || 20&nbsp;mg
|-
| [[Morphine]] || {{abbr|IV|Intravenous administration}} || 10&nbsp;mg
|-
| [[Oxycodone]] || {{abbr|PO|Oral administration}} || 20&nbsp;mg
|-
| Oxymorphone || {{abbr|PO|Oral administration}} || 7–10&nbsp;mg
|-
| Oxymorphone || {{abbr|IV|Intravenous administration}} || 1&nbsp;mg
|}


===Pharmacokinetics===
Other manufacturers and Endo themselves have also, according to reports in the mass media and professional journals over the last few years, considered and/or are currently developing a Duragesic-style oxymorphone skin plasters and oxymorphone and hydromorphone nasal sprays.
{{See also|Oxycodone#Metabolism}}


==Illicit Use==
==Chemistry==
Oxymorphone is commercially produced from [[thebaine]], which is a minor constituent of the [[opium poppy]] (''Papaver somniferum'') but thebaine is found in greater abundance (3%) in the roots of the [[oriental poppy]] (''Papaver orientale'').<ref name = OUP09/><ref>{{cite journal | vauthors = Corrigan D, Martyn EM | title = The thebaine content of ornamental poppies belonging to the papaver section oxytona | journal = Planta Medica | volume = 42 | issue = 1 | pages = 45–9 | date = May 1981 | pmid = 17401879 | doi = 10.1055/s-2007-971544 | s2cid = 43030595 }}</ref>
Like other effective centrally-acting analgesics, some of the additional effects of oxymorphone can include euphoria, anxiolysis, promotion of sociability, and other similar effects that can cause psychological addiction to the drug. Also, like all other opiates, oxymorphone is physically addictive and can cause opiate withdrawal symptoms.
German patents from the mid-1930s indicate that oxymorphone as well as [[hydromorphone]], [[hydrocodone]], [[oxycodone]], and [[acetylmorphone]] can be prepared—without the need for hydrogen gas—from solutions of [[codeine]], [[morphine]], and [[dionine]] by refluxing an acidic aqueous solution, or the precursor drug dissolved in [[ethanol]], in the presence of certain metals, namely [[palladium]] and [[platinum]] in fine powder or colloidal form or platinum black.


Oxymorphone hydrochloride occurs as odourless white crystals or white to off-white powder. It darkens in colour with prolonged exposure to light. One gram of oxymorphone hydrochloride is soluble in 4&nbsp;ml of water and it is sparingly soluble in alcohol and ether. It degrades upon contact with light.<ref name = MD/>
Opana ''does'' have euphoric effects, and they are short-lived. This is one of the crucial elements of a drug that can generate a serious narcotic habit rather quickly in those who take it for recreation and require more doses to maintain a stable level of euphoria. These effects however, barring enhancement with alcohol or other substances or means of administration other than oral, are less pronounced than that of morphine, fentanyl or dilaudid however, as mentioned previously, when taken intranasally the euphoric effects are far more pronounced.


Oxymorphone can be acetylated like morphine, hydromorphone, and some other opioids. Mono-, di-, tri-, and tetra- esters of oxymorphone were developed in the 1930s but are not used in medicine at this time. Presumably other esters such as nicotinyl, benzoyl, formyl, cinnimoyl &c.can be produced.{{citation needed|date=June 2017}}
The significant [[antidepressant]] and [[empathogenic]] properties of oxymorphone and other dihydromorphinone class semi-synthetic opioids is currently of interest to both the underground and the medical establishment, the latter of whom are "re-discovering" the anti-depressant effect and its relatively low ratio of toxic effects and lack of association with patient suicide attempts (see the [[oxycodone|oxycodone discussion]] for further information and footnotes) and Opana ER has been proposed as an alternative to methadone and other extended-release and/or long lasting drugs like [[Morphine]], extended-release dihydrocodeine, buprenorphine, and 24-hour hydromorphone tablets for opioid detoxification and maintenance.


The 2013 US [[Drug Enforcement Administration|DEA]] annual manufacturing quotas were 18 375 kilogrammes for conversion (a number of drugs can be made from oxymorphone, both painkillers and [[opioid antagonist]]s like [[naloxone]]) and 6875&nbsp;kg for direct manufacture of end-products.<ref>{{cite web|url=http://www.deadiversion.usdoj.gov/fed_regs/quotas/2013/fr0620.htm|title=2013 – Proposed Adjustments to the Aggregate Production Quotas for Schedule I and II Controlled Substances and Assessment of Annual Needs for the List I Chemicals Ephedrine, Pseudoephedrine, and Phenylpropanolamine for 2013|website=www.deadiversion.usdoj.gov|language=en-US|access-date=2014-05-03|archive-date=2017-05-14|archive-url=https://web.archive.org/web/20170514115234/https://www.deadiversion.usdoj.gov/fed_regs/quotas/2013/fr0620.htm|url-status=dead}}</ref> Oxymorphone is also a minor metabolite of [[oxycodone]], which is formed by [[CYP2D6]]-mediated O-demethylation.<ref name="OUP09" />
Endo withdrew the original Numorphan tablets from the market in 1972 as the result of regulatory and market pressures and other considerations as it was passionately sought, by any means necessary, by some narcotics addicts. Until its removal from the United States market at that point, oxymorphone in the form of Numorphan 10&nbsp;mg instant-release tablets was one of the most sought-after and well-regarded opioids of the [[Intravenous therapy|IV]] drug using community. Because of its low bioavailability, 10% when taken orally, a 10&nbsp;mg tablet represents 10 times the average IV dose in a single tablet. Known popularly as "blues" or "Nu- Blues" for their light blue color, the tablets contained very few insoluble binders—making them easy to inject—and were extremely potent when used intravenously. "Blues" were also considered to be especially euphoric; comparable to or better than heroin. Numorphan tablets, and the oxymorphone they contained, are the "blues" referred to in the film ''[[Drugstore Cowboy]]''.


==History==
Slang terms for oxymorphone include: blues, biscuits, blue heaven, new blues (although the immediate-release tablets are pink and off-white), octagons (extended release), [strength] octagons, stop signs, pink, pink heaven, biscuits (could also be Dilaudid tablets, [[meprobamate]] tablets, or formerly [[Quaaludes]]), pink heaven, pink lady, Mrs O, Orgasna IR, OM, Pink O, The O Bomb (by analogy to the slang term for hydromorphone "H Bomb") and others.
Oxymorphone was first developed in Germany in 1914,<ref>{{cite book| vauthors = Sinatra R |title=The Essence of Analgesia and Analgesics|year=2010|publisher=Cambridge University Press; 1 edition|location=MA, USA|isbn=978-0521144506|page=123|url=https://books.google.com/books?id=ZwPIjKg0XukC&q=oxymorphone+1914+germany&pg=PA123}}</ref> and patented in the US by [[Endo Pharmaceuticals]] in 1955.<ref>{{cite patent | country = US
| number = 2806033 | status = patent | title = Morphine derivative | pubdate = 8 March 1955 | gdate = 1957-10-09 | inventor = Leweustein MJ }}</ref> It was introduced in the United States in January 1959 and other countries around the same time.<ref name = OUP09/>


==Society and culture==
Oxymorphone is not a component of "[[Pentazocine|T's and blues]]", 1970s slang for a combination of [[pentazocine]] ("''T's''") and [[pyribenzamine]] ("''blues''"). Nor are "blues" 10&nbsp;mg Valium tablets, which are known as Blue Bombers and BBs.


===Brand names===
<!-- The following sentence has been commented out not only because it is a run-on sentence, but also because it makes no sense. If that info is to be kept as part of the entry, it needs to be made legible. -->
* Numorphan (suppository and injectable solution)
<!--Oxymorphone was available in the United States only as suppositories and ampoules for hospital use for 35 years until recently, making diversion of the ampoules and the time-consuming proceess of melting, mixing with water, then chilling the suppositories and drawing off the aqueous portion of the results and boiling down as the major means of use of oxymorphone pharmaceuticals in means inconsistent with their labeling in the USA.-->
* Opana ER (extended-release tablet): June 2017 FDA removal request due to rates of IV abuse.<ref name="FDA_2017_Endo">{{cite press release |date=8 June 2017 |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm562401.htm |title=FDA requests removal of Opana ER for risks related to abuse |type=Press release |location=[[Silver Spring, Maryland]]|agency=U.S. Food and Drug Administration |access-date=26 October 2017 |quote="Today, the U.S. Food and Drug Administration requested that Endo Pharmaceuticals remove its opioid pain medication, reformulated Opana ER (oxymorphone hydrochloride), from the market... This is the first time the agency has taken steps to remove a currently marketed opioid pain medication from sale due to the public health consequences of abuse...[FDA Commissioner Scott Gottlieb, M.D.]: "We are facing an opioid epidemic – a public health crisis, and we must take all necessary steps to reduce the scope of opioid misuse and abuse."}}</ref>
Rare cases of users baking their own at home by extracting oxycodone from pharmaceuticals and converting it to oxymorphone have been reported in a number of countries. In some cases, [[codeine]] is the starting material with morphine, or more rarely thebaine, being the intermediate. In those cases, the more common end products sought are morphine salts, morphine base, [[heroin]], [[dihydromorphine]], [[desomorphine]], and hydromorphone.
* Opana IR (immediate-release tablet)
* O-Morphon in Bangladesh by Ziska pharmaceutical ltd.


The brand name Numorphan is derived by analogy to the Nucodan name for an [[oxycodone]] product (or vice versa) as well as Paramorphan/Paramorfan for [[dihydromorphine]] and Paracodin ([[dihydrocodeine]]). The only commercially available salt of oxymorphone in most of the world at this time is the [[hydrochloride]], which has a free base conversion ratio of 0.891, and oxymorphone hydrochloride monohydrate has a factor of 0.85.<ref name = MD/>
The low bioavailability of oxymorphone after oral administration requires Opana extended-release to contain up to 40&nbsp;mg of oxymorphone per tablet—almost as much as an entire case of Numorphan ampoules; attempts to circumvent the extended-release mechanism by injecting or snorting the tablets are therefore particularly dangerous. However, chewing the tablets and/or taking with alcohol for the 70 per cent bioavailability boost from the latter appear to be the only means successful Opana ER misuse aside from [[Insufflation (medicine)|insufflation]] -- the TIMERx system appears to be making the extended release tablets useless for preparing for injection.


Generic pill markings are ATV10/APO; HK10 (10&nbsp;mgs) oblong white and ATV20/APO; HK20 (20&nbsp;mgs) oblong white.{{citation needed|date=June 2017}}
==Chemistry==
Oxymorphone is commercially produced from [[thebaine]], which is a minor constituent of the [[opium poppy]] (''Papaver somniferum'') but thebaine is found in greater abundance (3%) in the roots of the [[oriental poppy]] (''Papaver orientale''). Oxymorphone can also be synthesized from morphine or [[oxycodone]], and is an active metabolite of the latter drug. The [[Quantitative structure-activity relationship|structure-activity relationship]] of oxymorphone and its derivatives has been well-examined. [[Esterification]] of the [[hydroxyl]] groups yields stronger compounds. Another derivative of oxymorphone is the narcotic antagonist [[naloxone]] (Narcan).


===Abuse===
As reported in the July 1993 issue of Applied Environmental Bacteriology (PDF available at http://aem.asm.org/cgi/reprint/61/10/3645.pdf), the bacterium ''Pseudomonas putida'', serotype M10 turns oxymorphone into [[oxymorphol]] by means of a one-step conversion involving morphine dehydrogenase and a naturally occurring NADH-dependent morphinone reductase that can work on unsaturated 7,8 bonds.
In 1924, the United States banned the sale and importation of opium for the manufacture of heroin, an opioid pain medication which was being abused. See [[Anti-Heroin Act of 1924]].{{Relevance|date=November 2023}}


Beginning in the 1990s, [[Opioid_epidemic|prescription opioid drug abuse]] has been a prevalent public health issue of concern.<ref>{{cite web|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6043a4.htm|title=Vital Signs: Overdoses of Prescription Opioid Pain Relievers --- United States, 1999—2008| vauthors = Paulozzi, Leonard J MD |date=4 November 2011|website=CDC|access-date=25 June 2023}}</ref> Since 2013, with greatly increasing [[morbidity]] and deaths from overdoses of ''synthetic'' opioids, such as [[oxycodone]], [[tramadol]], and [[fentanyl]], this issue has developed into a full-fledged epidemic.<ref>{{cite web|url=https://www.cdc.gov/opioids/basics/epidemic.html|title=Understanding the Opioid Overdose Epidemic| author = Centers for Disease Control and Prevention |date=1 June 2022|website=CDC|access-date=25 June 2023}}</ref> This has led to several other public health issues, including the spread of diseases like [[hepatitis C]] and human immunodeficiency virus (HIV).<ref name="medium">{{cite web|url=https://medium.com/addiction-unscripted/injecting-opana-indiana-s-hiv-outbreak-and-america-s-opioid-epidemic-65501f9aa6c8|title=Injecting Opana: Indiana's HIV Outbreak and America's Opioid Epidemic| vauthors = Raymond D |date=2 March 2015|website=Medium|access-date=2 November 2018}}</ref><ref name="npr">{{cite news | vauthors = Dreisbach T | date = 16 March 2017 |url= https://www.npr.org/sections/health-shots/2017/03/16/520291362/dangers-of-opana-opioid-painkiller-outweigh-benefits-fda-panel-says |title=Dangers Of Opana Opioid Painkiller Outweigh Benefits, FDA Panel Says|work=NPR.org|access-date=2 November 2018|language=en}}</ref>
German patents from the middle 1930s indicate that oxymorphone as well as [[hydromorphone]], [[hydrocodone]], [[oxycodone]], and [[acetylmorphone]] can be prepared—without the need for hydrogen gas—from solutions of [[codeine]], [[morphine]], and [[dionine]] by refluxing an acidic aqueous solution, or the precursor drug dissolved in [[ethanol]], in the presence of Column 7 metals, namely [[palladium]] and [[platinum]] in fine powder or colloidal form or platina black. It is unclear from information available if [[aluminium]] or [[nickel]] can be used as a catalyst in these reactions as well.


In the United States, as of 2013 more than 12&nbsp;million people abused opioid drugs at least once a year.<ref name="Girioin">{{cite news| vauthors = Girioin L, Haely M |title=FDA to require stricter labeling for pain drugs|newspaper=Los Angeles Times|date=11 September 2013 |pages=A1 and A9}}</ref> In 2010, 16,652 deaths were related to opiate overdose, in 2015 this number increased to 33,091.<ref>{{cite web|title=Drug Overdose in the United States: Fact Sheet|url=https://www.cdc.gov/homeandrecreationalsafety/overdose/facts.html|publisher=Centers for Disease Control|access-date=12 September 2013}}</ref><ref>{{cite journal | vauthors = Rudd RA, Seth P, David F, Scholl L | title = Increases in Drug and Opioid-Involved Overdose Deaths – United States, 2010–2015 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 65 | issue = 50–51 | pages = 1445–1452 | date = December 2016 | pmid = 28033313 | doi = 10.15585/mmwr.mm655051e1 | doi-access = free }}</ref> In September 2013, new FDA labeling guidelines for long-acting and extended-release opioids required manufacturers to remove moderate pain as use indication, reserving the drug for "pain severe enough to require daily, around-the-clock, long-term opioid treatment"<ref>{{cite web|title=ER/LA Opioid Class Labeling Changes and Postmarket Requirements |url= https://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM367697.pdf |publisher=FDA |access-date=12 September 2013}}</ref> however it did not restrict physicians from prescribing opioids for moderate, "as needed" usage.<ref name="Girioin" />
A discussion of the above can be found at http://www.erowid.org/archive/rhodium/chemistry/dihydromorphinones.html (English). However, the aforementioned patents deal specifically with hydrogenation reactions producing dihydrocodeinone (hydrocodone), dihydromorphinone (hydromorphone), and ethyldihydromorphinone as final products. Hence it is unclear at best and rather unlikely that these particular procedures can be applied for the synthesis of oxycodone or oxymorphone, as they are not typically synthesized in this manner.


In January 2013, the Centers for Disease Control and Prevention (CDC) reported an illness associated with intravenous (IV) abuse of oral Opana ER (oxymorphone) in Tennessee. The syndrome resembled that of [[thrombotic thrombocytopenic purpura]] (TTP).<ref>{{cite journal | vauthors = Marder E, Kirschke D, Robbins D, Dunn J, Jones TF, Racoosin J, Paulozzi L, Chang A | title = Thrombotic thrombocytopenic purpura (TTP)-like illness associated with intravenous Opana ER abuse—Tennessee, 2012 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 62 | issue = 1 | pages = 1–4 | date = January 2013 | pmid = 23302815 | pmc = 4604918 | url = https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6201a1.htm }}</ref> Initial therapy included therapeutic [[plasma exchange]], as for TTP. Unlike TTP, no deficient [[ADAMTS13]] activity nor anti-ADAMTS13 antibody was found indicating a [[thrombotic microangiopathy]] of different underlying cause. If IV Opana abuse is acknowledged, supportive care, instead of therapeutic plasma exchange could be considered.<ref>{{cite journal | vauthors = Miller PJ, Farland AM, Knovich MA, Batt KM, Owen J | title = Successful treatment of intravenously abused oral Opana ER-induced thrombotic microangiopathy without plasma exchange | journal = American Journal of Hematology | volume = 89 | issue = 7 | pages = 695–7 | date = July 2014 | pmid = 24668845 | doi = 10.1002/ajh.23720 | s2cid = 27414213 | doi-access = free }}</ref>
The rare practise of making homebake oxymorphone generally uses oxycodone and [[pyridine]] amongst others, and the production of homebake hydromorphone (Dilaudid) from hydrocodone does also exist but is extremely rare. This is similar to a method especially common in New Zealand to make morphine out of [[codeine]]. The resultant morphine base is used as is, made into a salt (usually citrate, although ascorbate, acetate, hydrochloride, nitrate, phosphate, and sulphate are also possible) by dissolving the base in a solution containing the relevant acid, or treated with [[acetic anhydride]] or rarely other chemicals capable of acetylating compounds to produce what is usually a mixture of heroin, morphine, 3-monoacetylmorphine and 6-monoacetylmorphine. Depending on the method, this can also contain [[acetylcodeine]] and leftover codeine.


In January 2015, the first HIV outbreak linked to abuse of prescription opioid drugs was identified by the Indiana State Department of Health (ISDH), in the small, rural community of Scott County in southeastern Indiana.<ref name="cdc">{{cite web|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6416a4.htm|title=Community Outbreak of HIV Infection Linked to Injection Drug Use of Oxymorphone — Indiana, 2015|website=www.cdc.gov|language=en|access-date=2 November 2018}}</ref> &nbsp;ISDH launched an investigation into this HIV outbreak when 11 individuals were confirmed positive for HIV with ties tracing back to the same community. Three months into this investigation, ISDH diagnosed a total of 135 people with HIV, with the numbers still increasing. The cause of this outbreak has been linked to the sharing of needles between opioid abusers, which in some cases, involves sharing needles with up to nine different partners.<ref name="npr"/>
==See also==

* [[Opioids]]
In late March 2015, reports indicated [[Austin, Indiana]], was the center of an outbreak of HIV caused by oxymorphone use as an injectable recreational drug. The outbreak required emergency action by state officials.<ref>{{cite news|url=https://www.washingtonpost.com/blogs/wonkblog/wp/2015/03/30/how-an-hiv-outbreak-hit-rural-indiana-and-why-we-should-be-paying-attention/|title=How an HIV outbreak hit rural Indiana — and why we should be paying attention| vauthors = Paquette D |date=30 March 2015|access-date=1 April 2015|newspaper=Washington Post}}</ref><ref>{{cite journal | vauthors = Conrad C, Bradley HM, Broz D, Buddha S, Chapman EL, Galang RR, Hillman D, Hon J, Hoover KW, Patel MR, Perez A, Peters PJ, Pontones P, Roseberry JC, Sandoval M, Shields J, Walthall J, Waterhouse D, Weidle PJ, Wu H, Duwve JM | display-authors = 6 | title = Community Outbreak of HIV Infection Linked to Injection Drug Use of Oxymorphone—Indiana, 2015 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 64 | issue = 16 | pages = 443–4 | date = May 2015 | pmid = 25928470 | pmc = 4584812 | collaboration = Centers for Disease Control Prevention (CDC) }}</ref><ref>{{cite journal | vauthors = Strathdee SA, Beyrer C | title = Threading the Needle—How to Stop the HIV Outbreak in Rural Indiana | journal = The New England Journal of Medicine | volume = 373 | issue = 5 | pages = 397–9 | date = July 2015 | pmid = 26106947 | doi = 10.1056/NEJMp1507252 | doi-access = free }}</ref> The NPR podcast "embedded" episode of 31 March 2016 was an in-depth account of a visit to oxymorphone abusers in Austin, Indiana. In 2016, the street price of oxymorphone was reported to be $140.<ref>{{cite news|url=https://www.npr.org/podcasts/510311/embedded|title=Embedded| vauthors = McEvers K |date=31 March 2016|work=NPR.org|language=en}}</ref>
* [[Oxymorphazone|Oxymorphone hydrazone]]

* [[Oxymorphol]] - a metabolite of oxymorphone and an intermediate in the creation of hydromorphone
The common opioid of abuse in this outbreak has been identified as Opana ER, a time-released oxymorphone pain killer formulated to be resistant to crushing, manufactured by Endo Pharmaceuticals. This harder to crush formulation was put into production in 2012 in an effort to reduce the risk of abuse from snorting the crushed up pill. However, opioid abusers circumvented this issue by finding a way to dissolve and inject the drug.<ref name="cdc"/>
* [[Hydromorphone]]

* [[Oxycodone]]
The extent of this outbreak has garnered the attention of both the CDC and FDA. The CDC opened a larger investigation into all disease outbreaks involving Opana ER, focusing on the incidence of thrombotic thrombocytopenic purpura (TTP)-like illness in the 2012 Tennessee outbreak, as well as the 2015 HIV outbreak in Indiana. The FDA launched a post-marketing safety study regarding the reformulation of Opana ER in 2012<ref name="fda">{{cite web | url = https://www.fda.gov/files/advisory%20committees/published/FDA-Briefing-Information-for-the-March-13-14--2017-Joint-Meeting-of-the-Drug-Safety-and-Risk-Management-Advisory-Committee-and-the-Anesthetic-and-Analgesic-Drug-Products-Advisory-Committee.pdf | vauthors = Staffa J | date = 13 March 2017 | work = Joint Meeting of the Drug Safety and Risk Management (DSaRM) Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) Meeting | title = Postmarketing Safety Issues Related to Reformulated Opana ER | location = United States | publisher = US Food and Drug Administration, Surveillance and Epidemiology }}</ref> and the Indiana state government helped fund another study exploring the link between HIV infection and injection use of oxymorphone in Indiana from 2014 to 2015.<ref name="HIV Infection">{{cite journal | vauthors = Peters PJ, Pontones P, Hoover KW, Patel MR, Galang RR, Shields J, Blosser SJ, Spiller MW, Combs B, Switzer WM, Conrad C, Gentry J, Khudyakov Y, Waterhouse D, Owen SM, Chapman E, Roseberry JC, McCants V, Weidle PJ, Broz D, Samandari T, Mermin J, Walthall J, Brooks JT, Duwve JM | display-authors = 6 | title = HIV Infection Linked to Injection Use of Oxymorphone in Indiana, 2014–2015 | language = EN | journal = The New England Journal of Medicine | volume = 375 | issue = 3 | pages = 229–39 | date = July 2016 | pmid = 27468059 | doi = 10.1056/nejmoa1515195 | doi-access = free | hdl = 1805/12238 | hdl-access = free }}</ref>
* [[Drug addiction]]

The results of these studies found that the reformulation of Opana to a hard to crush tablet unintentionally increased the risk of transmission of acquired blood borne infections because opioid abusers switched from using the drug through the nasal route to injection. This epidemic caused the risk of acquiring a blood borne infection with the use of injectable opioids to increase in comparison to the risk of acquiring an infection when using injectable heroin or cocaine.<ref name="medium"/><ref name="fda"/><ref name="HIV Infection"/>

In June 2017, faced with the public health crisis, the opioid epidemic, the FDA asked [[Endo Pharmaceuticals]] to "remove its opioid pain medication, reformulated Opana ER (oxymorphone hydrochloride), from the market". In their 8 June 2017 press release they also noted that, this was the first time the FDA had taken steps to "remove a currently marketed opioid pain medication from sale due to public health consequences of abuse."<ref name="FDA_2017_Endo"/> By 6 July 2017, Endo International voluntarily complied with the FDA removal request.<ref name="fiercepharma_2017">{{cite web |url=http://www.fiercepharma.com/regulatory/endo-caves-to-fda-pressure-to-pull-opana-er-from-market |title=Endo caves to FDA pressure, will pull Opana ER from the market | vauthors = Palmer E |date= 6 July 2017 |access-date=26 October 2017 |work=Fierce Pharma}}</ref>

== See also ==
* [[Oxymorphazone]]
* [[Oxymorphol]]


== References ==
== References ==
{{Reflist}}
<references/>


{{Analgesics}}
{{Analgesics}}
{{Opioid receptor modulators}}
{{Opioids}}


{{Commons category-inline}}
[[Category:Morphinans]]

[[Category:Semisynthetic opioids]]
[[Category:Tertiary alcohols]]
[[Category:Cyclohexanols]]
[[Category:4,5-Epoxymorphinans]]
[[Category:Ethers]]
[[Category:Euphoriants]]
[[Category:German inventions]]
[[Category:German inventions]]
[[Category:Phenols]]
[[Category:Ketones]]
[[Category:Ketones]]
[[Category:Alcohols]]
[[Category:Mu-opioid receptor agonists]]
[[Category:Ethers]]
[[Category:Phenols]]
[[Category:Mu-opioid agonists]]
[[Category:Semisynthetic opioids]]

[[de:Oxymorphon]]
[[fr:Oxymorphone]]
[[ru:Оксиморфон]]
[[fi:Oksimorfoni]]
[[sv:Oximorfon]]
[[th:ออกซิมอร์ฟีน]]
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