oxymorphone

Oxymorphone Immediate Release is indicated for the relief of moderate to severe pain, such as treatment of acute post-surgical pain.{{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 = 777–787 | date = August 2008 | pmid = 19209260 | pmc = 2621383 | doi = 10.2147/TCRM.S1784 | doi-access = free }} 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.{{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 }}

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.{{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 }}

In the United States it is a Schedule II controlled substance with an ACSCN of 9652.{{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 }}

Oxymorphone ER Tablets should be taken on an empty stomach.{{Cite web | title = Oxymorphone ER Tablet | url = https://my.clevelandclinic.org/health/drugs/18265-oxymorphone-er-tablet | website = ClevelandClinic.org }}

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 Opana ER was withdrawn by the manufacturer in 2017 due to an FDA request, making it unavailable in the US.{{cite web | vauthors = Barrett J | title = Endo to Pull Opana From the Market Following FDA Request. | date = 6 July 2017 | work = Pharmacy Times. | 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 }} However, both IR (immediate release) and ER (extended release) formulations are still available under the generic names Oxymorphone and Oxymorphone ER and available from a multitude of manufacturers.

Oxymorphone is also available as an injectable for inpatient use, available for IV (intravenous), IM (intramuscular), and SC (subcutaneous) injection.

An extended release (ER) modified-release dosage form is commonly used, which modifies the pharmacokinetics of the drug.

Oxymorphone comes in a variety of doses.

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.

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.{{cite web | title = Login | url = http://www.crlonline.com/lco/action/doc/retrieve/docid/patch_f/7423#pri | website = www.crlonline.com | language = en-US | access-date = 1 November 2018 }}

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.{{cite web | veditors = Brayfield A | title = Oxymorphone Hydrochloride | date = 30 January 2013 | work = Martindale: The Complete Drug Reference | publisher = Pharmaceutical Press | access-date = 5 May 2014 | url = http://www.medicinescomplete.com/mc/martindale/current/6249-a.htm }}

In common with other opioids, oxymorphone overdosage is characterized by respiratory depression, sleepiness progressing to stupor or coma, skeletal muscle weakness, cold and clammy skin, and sometimes slow heart rate and low blood pressure. In a severe case of overdose, apnea, circulatory collapse, cardiac arrest and death can occur.

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). Its activity at the DOR may augment its action at the MOR. Oxymorphone is 10 times more potent than morphine.{{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 }} Calculation of relative potency indicates that 1 mg of oxymorphone hydrochloride is equivalent to 9.85 mg of morphine sulfate, or equivalently, 1.02 mg of oxymorphone hydrochloride is equivalent to 10 mg of morphine sulfate.{{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 | doi = 10.1016/S0022-3565(25)12962-5 | pmid = 13631610 | url = https://pubmed.ncbi.nlm.nih.gov/13631610/ | access-date = 14 July 2021 }}

{{See also|Oxycodone#Metabolism}}

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).{{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 = 45–49 | date = May 1981 | pmid = 17401879 | doi = 10.1055/s-2007-971544 | bibcode = 1981PlMed..42...45C | s2cid = 43030595 }}

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 ml of water and it is sparingly soluble in alcohol and ether. It degrades upon contact with light.

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 2013 US DEA annual manufacturing quotas were 18 375 kilogrammes for conversion (a number of drugs can be made from oxymorphone, both painkillers and opioid antagonists like naloxone) and 6875 kg for direct manufacture of end-products.{{cite web | 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 | url = http://www.deadiversion.usdoj.gov/fed_regs/quotas/2013/fr0620.htm | 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 }} Oxymorphone is also a minor metabolite of oxycodone, which is formed by CYP2D6-mediated O-demethylation.

Oxymorphone was first developed in Germany in 1914,{{cite book | vauthors = Sinatra R | title = The Essence of Analgesia and Analgesics | location = MA, USA | pages = 123 | year = 2010 | publisher = Cambridge University Press; 1 edition | isbn = 978-1-139-49198-3 | url = https://books.google.com/books?id=ZwPIjKg0XukC&q=oxymorphone+1914+germany&pg=PA123 }} and patented in the US by Endo Pharmaceuticals in 1955.{{cite patent | title = Morphine derivative | number = 2806033 | country = US | status = patent | pubdate = 8 March 1955 | gdate = 1957-10-09 | inventor = Leweustein MJ }} It was introduced in the United States in January 1959 and other countries around the same time.

• Numorphan (suppository and injectable solution)
• Opana ER (extended-release tablet): June 2017 FDA removal request due to rates of IV abuse.{{cite press release |title=FDA requests removal of Opana ER for risks related to abuse |date=8 June 2017 |location=Silver Spring, Maryland |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm562401.htm |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." |access-date=26 October 2017 |archive-url=https://web.archive.org/web/20190505210836/https://www.fda.gov/news-events/press-announcements/fda-requests-removal-opana-er-risks-related-abuse |archive-date=5 May 2019 |type=Press release |agency=U.S. Food and Drug Administration}}
• 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.

Generic pill markings are ATV10/APO; HK10 (10 mgs) oblong white and ATV20/APO; HK20 (20 mgs) oblong white.{{citation needed|date=June 2017}}

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 inline|date=November 2023}}

Beginning in the 1990s, prescription opioid drug abuse has been a prevalent public health issue of concern.{{cite web | vauthors = Paulozzi, Leonard J MD | title = Vital Signs: Overdoses of Prescription Opioid Pain Relievers --- United States, 1999—2008 | date = 4 November 2011 | url = https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6043a4.htm | website = CDC | access-date = 25 June 2023 }} 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.{{cite web | vauthors = ((Centers for Disease Control and Prevention)) | title = Understanding the Opioid Overdose Epidemic | date = 1 June 2022 | url = https://www.cdc.gov/opioids/basics/epidemic.html | website = CDC | access-date = 25 June 2023 }} This has led to several other public health issues, including the spread of diseases like hepatitis C and human immunodeficiency virus (HIV).{{cite news | vauthors = Dreisbach T | title = Dangers Of Opana Opioid Painkiller Outweigh Benefits, FDA Panel Says | 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 | work = NPR.org | access-date = 2 November 2018 | language = en }}{{verify source|date=May 2025}}

In the United States, as of 2013 more than 12 million people abused opioid drugs at least once a year.{{cite news | vauthors = Girioin L, Haely M | title = FDA to require stricter labeling for pain drugs | pages = A1 and A9 | date = 11 September 2013 | newspaper = Los Angeles Times }} In 2010, 16,652 deaths were related to opiate overdose, in 2015 this number increased to 33,091.{{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 }}{{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 }} 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"{{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 }}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}} however it did not restrict physicians from prescribing opioids for moderate, "as needed" usage.

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).{{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 }} 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.{{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 = 695–697 | date = July 2014 | pmid = 24668845 | doi = 10.1002/ajh.23720 | s2cid = 27414213 | doi-access = free }}

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.{{cite web | title = Community Outbreak of HIV Infection Linked to Injection Drug Use of Oxymorphone — Indiana, 2015 | url = https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6416a4.htm | website = www.cdc.gov | language = en | access-date = 2 November 2018 }}  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.

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.{{cite news | vauthors = Paquette D | title = How an HIV outbreak hit rural Indiana — and why we should be paying attention | date = 30 March 2015 | 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/ | access-date = 1 April 2015 | newspaper = Washington Post }}{{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 | 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 = 443–444 | date = May 2015 | pmid = 25928470 | pmc = 4584812 | collaboration = Centers for Disease Control Prevention (CDC) }}{{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 = 397–399 | date = July 2015 | pmid = 26106947 | doi = 10.1056/NEJMp1507252 | doi-access = free }} 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.{{cite news | vauthors = McEvers K | title = Embedded | date = 31 March 2016 | url = https://www.npr.org/podcasts/510311/embedded | work = NPR.org | language = en }}

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.

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{{cite web | vauthors = Staffa J | title = Postmarketing Safety Issues Related to Reformulated Opana ER | location = United States | date = 13 March 2017 | 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 | archive-url = https://web.archive.org/web/20211025180207/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 | url-status = dead | archive-date = 25 October 2021 | work = Joint Meeting of the Drug Safety and Risk Management (DSaRM) Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) Meeting | publisher = US Food and Drug Administration, Surveillance and Epidemiology }} 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.{{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 | title = HIV Infection Linked to Injection Use of Oxymorphone in Indiana, 2014–2015 | journal = The New England Journal of Medicine | volume = 375 | issue = 3 | pages = 229–239 | date = July 2016 | pmid = 27468059 | doi = 10.1056/nejmoa1515195 | language = EN | doi-access = free | hdl = 1805/12238 | hdl-access = free }}

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.{{verify source|date=May 2025}}

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." By 6 July 2017, Endo International voluntarily complied with the FDA removal request.{{cite web | vauthors = Palmer E | title = Endo caves to FDA pressure, will pull Opana ER from the market | date = 6 July 2017 | url = http://www.fiercepharma.com/regulatory/endo-caves-to-fda-pressure-to-pull-opana-er-from-market | access-date = 26 October 2017 | work = Fierce Pharma }}

Oxymorphone provides 5–6 hours of analgesia when adminstered intravenously to cats and dogs. Oxymorphone is ineffective when give via oral-transmucosal. Little data exists regarding oxymorphone in large animals and equines due to oxymorphone's higher cost.{{cite book | vauthors = Simon BT, Lizarraga I | chapter = Opioids | title = Veterinary Anesthesia and Analgesia, The 6th Edition of Lumb and Jones | date = 11 September 2024 | pages = 378 | isbn = 978-1-119-83027-6 | veditors = Lamont L, Grimm K, Robertson S, Love L, Schroeder C | publisher = Wiley Blackwell }}

• Oxymorphazone
• Oxymorphol

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Category:4,5-Epoxymorphinans

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Category:German inventions

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Category:Mu-opioid receptor agonists

Category:Hydroxyarenes

Category:Semisynthetic opioids