Oxymorphone
Clinical data | |
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Trade names | Numorphan, Numorphone, Opana, others |
Other names | 14-Hydroxydihydromorphinone |
AHFS/Drugs.com | Monograph |
MedlinePlus | a610022 |
License data |
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Dependence liability | High |
Addiction liability | High |
Routes of administration | By mouth, buccal, sublingual, intranasal, intravenous, epidural, subcutaneous, intramuscular |
Drug class | Opioid |
ATC code | |
Legal status | |
Legal status |
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Pharmacokinetic data | |
Bioavailability | by mouth: 10% Buccal: 28% Sublingual: 37.5% Intranasal: 43%[3] IV, IM & IT: 100%[4] |
Protein binding | 10%[4] |
Metabolism | Liver (CYP3A4, glucuronidation)[4] |
Elimination half-life | 7–9 hours[4] |
Duration of action | Duration of action: 6–8 hours orally, 4–6 hrs parenteral |
Excretion | Urine, feces[4] |
Identifiers | |
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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.[5] The elimination half-life of oxymorphone is much faster intravenously, and as such, the drug is most commonly used orally.[6] Like oxycodone, which metabolizes to oxymorphone, oxymorphone has a high potential to be abused.[7]
It was developed in
Medical uses
Oxymorphone Immediate Release is indicated for the relief of moderate to severe pain, such as treatment of acute post surgical pain.[12] 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.[13]
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.[14]
In the United States it is a Schedule II controlled substance with an
Oxymorphone ER Tablets should be taken on an empty stomach.[16]
Availability
Brands and forms
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
Oxymorphone is also available as an injectable for inpatient use, available for IV (
An extended release (ER) modified-release dosage form is commonly used, which modifies the pharmacokinetics of the drug.
Oral dosage forms
Oxymorphone comes in a variety of doses.
IR Tablet[18] | ER 12 Hour Tablet[18] |
---|---|
5 mg | 5 mg |
10 mg | 7.5 mg |
10 mg | |
15 mg | |
20 mg | |
30 mg | |
40 mg |
Special populations
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.[19]
Side effects
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.[20]
Overdose
In common with other opioids, oxymorphone overdosage is characterized by respiratory depression, sleepiness progressing to stupor or coma, skeletal muscle
Pharmacology
Pharmacodynamics
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).[4] Its activity at the DOR may augment its action at the MOR.[4] Oxymorphone is 10 times more potent than morphine.[21] 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.[22]
Ki ) |
Ratio | ||
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MOR |
DOR |
KOR |
MOR:DOR:KOR |
0.78 nM | 50 nM | 137 nM | 1:64:176 |
Compound | Route | Dose |
---|---|---|
Codeine | PO | 200 mg |
Hydrocodone | PO | 20–30 mg |
Hydromorphone | PO | 7.5 mg |
Hydromorphone | IV | 1.5 mg |
Morphine | PO | 30 mg |
Oxycodone | IV | 20 mg |
Morphine | IV | 10 mg |
Oxycodone | PO | 20 mg |
Oxymorphone | PO | 7–10 mg |
Oxymorphone | IV | 1 mg |
Pharmacokinetics
Chemistry
Oxymorphone is commercially produced from
German patents from the mid-1930s indicate that oxymorphone as well asOxymorphone 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.[20]
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]
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.[28] Oxymorphone is also a minor metabolite of oxycodone, which is formed by CYP2D6-mediated O-demethylation.[4]
History
Oxymorphone was first developed in
Society and culture
Brand names
- Numorphan (suppository and injectable solution)
- Opana ER (extended-release tablet): June 2017 FDA removal request due to rates of IV abuse.[31]
- 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.[20]
Generic pill markings are ATV10/APO; HK10 (10 mgs) oblong white and ATV20/APO; HK20 (20 mgs) oblong white.[citation needed]
Abuse
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.[relevant?]
Beginning in the
In the United States, as of 2013 more than 12 million people abused opioid drugs at least once a year.[36] In 2010, 16,652 deaths were related to opiate overdose, in 2015 this number increased to 33,091.[37][38] 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"[39] however it did not restrict physicians from prescribing opioids for moderate, "as needed" usage.[36]
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
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.[42] 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.[35]
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.[43][44][45] The NPR podcast "embedded" episode of March 31, 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.[46]
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.[42]
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[47] 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.[48]
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.[34][47][48]
In June 2017, faced with the public health crisis, the opioid epidemic, the FDA asked
See also
References
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- ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
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- ^ Office of the Commissioner (2019-09-10). "Press Announcements – FDA requests removal of Opana ER for risks related to abuse". www.fda.gov.
- ^ Bernstein L, Merle R (2019-11-27). "Six drug companies subpoenaed in federal opioids probe". The Washington Post. Retrieved 18 April 2020.
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- ^ a b "Oxymorphone IR Package Insert" (PDF). Endo Pharmaceuticals. U.S. Food and Drug Administration. Retrieved 19 November 2018.
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- ^ US patent 2806033, Leweustein MJ, "Morphine derivative", published 1955-03-08, issued 1957-10-09
- ^ a b "FDA requests removal of Opana ER for risks related to abuse" (Press release). Silver Spring, Maryland. U.S. Food and Drug Administration. June 8, 2017. Retrieved 26 October 2017.
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.
- ^ Paulozzi, Leonard J MD (2011-11-04). "Vital Signs: Overdoses of Prescription Opioid Pain Relievers --- United States, 1999--2008". CDC. Retrieved 25 June 2023.
- ^ Centers for Disease Control and Prevention (2022-06-01). "Understanding the Opioid Overdose Epidemic". CDC. Retrieved 25 June 2023.
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- ^ a b Dreisbach T (16 March 2017). "Dangers Of Opana Opioid Painkiller Outweigh Benefits, FDA Panel Says". NPR.org. Retrieved 2 November 2018.
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- ^ Palmer E (July 6, 2017). "Endo caves to FDA pressure, will pull Opana ER from the market". Fierce Pharma. Retrieved 26 October 2017.
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