Oxymorphone Stats & Data
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DrugBankDescription
An opioid analgesic with actions and uses similar to those of morphine, apart from an absence of cough suppressant activity. It is used in the treatment of moderate to severe pain, including pain in obstetrics. It may also be used as an adjunct to anesthesia (From Martindale, The Extra Pharmacopoeia, 30th ed, p1092). On June 8, 2017, FDA requested Endo Pharmaceuticals to remove the medication from the market due to opioid misuse and abuse risks associated with the product's injectable reformulation.
Mechanism of Action
Oxymorphone interacts predominantly with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, with high densities in the posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical areas. They are also found on the terminal axons of primary afferents within laminae I and II (substantia gelatinosa) of the spinal cord and in the spinal nucleus of the trigeminal nerve. Also, it has been shown that oxymorphone binds to and inhibits GABA inhibitory interneurons via mu-receptors. These interneurons normally inhibit the descending pain inhibition pathway. So, without the inhibitory signals, pain modulation can proceed downstream.
Pharmacodynamics
Oxymorphone is a semi-synthetic opioid substitute for morphine. It is a potent analgesic. Opioid analgesics exert their principal pharmacologic effects on the CNS and the gastrointestinal tract. The principal actions of therapeutic value are analgesia and sedation. Opioids produce respiratory depression by direct action on brain stem respiratory centers. The mechanism of respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension and to electrical stimulation.
Metabolism
Oxymorphone undergoes extensive hepatic metabolism in humans. After a 10 mg oral dose, 49% was excreted over a five-day period in the urine. Of this, 82% was excreted in the first 24 hours after administration. The recovered drug-related products contained the oxymorphone (1.9%), the conjugate of oxymorphone (44.1%), the 6(beta)-carbinol produced by 6-keto reduction of oxymorphone (0.3%), and the conjugates of 6(beta)-carbinol (2.6%) and 6(alpha)-carbinol (0.1%).
Toxicity
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. Patients experiencing an overdose may develop apnea, circulatory collapse, and cardiac arrest. Intravenous mouse LD50 is 172 mg/kg.
Indication
For the treatment of moderate-to-severe pain.
Elimination
Oxymorphone is highly metabolized, principally in the liver, and undergoes reduction or conjugation with glucuronic acid to form both active and inactive products. Because oxymorphone is extensively metabolized, <1% of the administered dose is excreted unchanged in the urine.
Receptor Profile
Receptor Actions
Receptor Binding
History & Culture
1914–1959
Oxymorphone was first developed in Germany in 1914 as part of efforts to create opioid analgesics with improved side effect profiles compared to morphine and heroin. The compound exhibits actions and uses similar to morphine, though notably lacks cough suppressant activity. During the 1930s, researchers developed mono-, di-, tri-, and tetra-ester derivatives of oxymorphone, similar to acetylation processes used with morphine and hydromorphone, though none of these variants were adopted for medical use. The drug was patented in the United States by Endo Pharmaceuticals in 1955 and received approval for medical use in 1959, when it was introduced to the American market under the brand name Numorphan. This name was derived by analogy to other opioid product names including Nucodan for oxycodone, Paramorphan for dihydromorphine, and Paracodin for dihydrocodeine.
2012–2015
Prior to 2012, oxymorphone was commonly administered via insufflation among recreational users. In 2012, Endo Pharmaceuticals introduced a reformulated extended-release version of Opana designed to be crush-resistant, intended to reduce abuse through nasal administration. However, this reformulation had unintended consequences as users adapted by dissolving the tablets and injecting them intravenously. In January 2013, the Centers for Disease Control and Prevention reported an illness cluster associated with intravenous abuse of Opana ER in Tennessee, presenting with symptoms resembling thrombotic thrombocytopenic purpura. Subsequently, in January 2015, the Indiana State Department of Health identified the first HIV outbreak directly linked to prescription opioid abuse in Scott County, a small rural community in southeastern Indiana. By late March 2015, Austin, Indiana had become the epicenter of an HIV outbreak traced to injectable use of the reformulated Opana ER. Research into these events determined that the crush-resistant reformulation paradoxically increased the risk of blood-borne infection transmission by driving users from nasal to intravenous administration, ultimately creating greater public health risks than those associated with injectable heroin or cocaine.
2017–present
In June 2017, amid the escalating opioid epidemic and evidence that the 2012 reformulation had failed to prevent illicit injection, the FDA took the unprecedented step of requesting that Endo Pharmaceuticals voluntarily remove reformulated Opana ER from the United States market. By July 6, 2017, Endo International complied with this request, marking a significant regulatory action in response to the opioid crisis. Generic versions of extended-release oxymorphone remain available in the United States.
Effect Profile
Curated + 81 ReportsStrong euphoria, pain relief, and itching/nausea with moderate sedation
Empirical Duration
Erowid ReportsTolerance & Pharmacokinetics
drugs.wikiTolerance Decay
Cross-Tolerances
Demographics
Gender Distribution
Age Distribution
Reports Over Time
Effect Analysis
Erowid + BluelightEffects aggregated from 81 experience reports (71 Erowid + 10 Bluelight)
Effect Sentiment Distribution
Confidence Distribution
Positive Effects 17
Adverse Effects 15
Dose-Response Correlation
How effect frequency changes across dose levels
View data table
| Effect | Strong (n=14) | Heavy (n=21) |
|---|---|---|
| Euphoria | 57.1% | 52.4% |
| Nausea | 42.9% | 47.6% |
| Hospital | 28.6% | 33.3% |
| Empathy | 28.6% | 23.8% |
| Sedation | 28.6% | 28.6% |
| Sweating | 28.6% | 0% |
| Stimulation | 21.4% | 23.8% |
| Anxiety Suppression | 14.3% | 9.5% |
| Pain Relief | 0% | 14.3% |
| Headache | 0% | 9.5% |
| Music Enhancement | 0% | 9.5% |
| Body High | 0% | 9.5% |
| Dissociation | 0% | 9.5% |
| Focus Enhancement | 0% | 9.5% |
| Tactile Enhancement | 0% | 9.5% |
Dose–Effect Mapping
Experience ReportsHow reported effects shift across dose tiers, based on 71 experience reports.
Limited tier coverage — most reports fall within the Strong / Heavy range. Effects at other dose levels may not be represented.
| Effect | Strong (n=14) | Heavy (n=21) | |
|---|---|---|---|
| euphoria | → | ||
| nausea | → | ||
| hospital | ↑ | ||
| empathy | ↓ | ||
| sedation | → | ||
| sweating | — | → | |
| stimulation | → | ||
| anxiety suppression | ↓ | ||
| pain relief | — | → | |
| headache | — | → | |
| music enhancement | — | → | |
| body high | — | → | |
| dissociation | — | → | |
| focus enhancement | — | → | |
| tactile enhancement | — | → |
Risk Escalation
Sentiment AnalysisAverage frequency of positive vs adverse effects across dose tiers
View effect breakdown
Adverse Effects
| Effect | Strong (n=14) | Heavy (n=21) | Change |
|---|---|---|---|
| Nausea | 10% | ||
| Sweating | — | 0% | |
| Anxiety Suppression | -33% | ||
| Headache | — | 0% |
Positive Effects
| Effect | Strong (n=14) | Heavy (n=21) | Change |
|---|---|---|---|
| Euphoria | -8% | ||
| Empathy | -16% | ||
| Stimulation | +11% | ||
| Pain Relief | — | 0% | |
| Music Enhancement | — | 0% | |
| Body High | — | 0% | |
| Focus Enhancement | — | 0% | |
| Tactile Enhancement | — | 0% |
Dosage Distribution
Dose distribution from experience reports
Oral
Insufflated
Real-World Dose Distribution
62K DosesFrom 83 individual dose entries
Oral (n=14)
Intravenous (n=6)
Insufflated (n=59)
Common Combinations
Most co-occurring substances in experience reports
Form / Preparation
Most common forms and preparations reported
Body-Weight Dosing
Dose relative to body weight from reports with weight data
Oral
Insufflated
Redose Patterns
Redosing behavior across 64 reports
Opioid Equivalence (MME)
NIH HEAL 2024 & CDC 2022Oxymorphone 3.3 mg oral ≈ 10 mg Morphine oral
Legal Status
| Country | Status | Notes |
|---|---|---|
| Germany | Anlage II BtMG | Controlled under the Betäubungsmittelgesetz (Narcotics Act). Manufacturing, importing, possessing, selling, or transferring without a license is prohibited. Anlage II classification permits restricted medical use under appropriate authorization. |
| Russia | Schedule I | Classified as a Schedule I controlled substance under Russian drug control legislation. Possession, distribution, and manufacturing without authorization are prohibited. |
| Switzerland | Verzeichnis A | Listed under Verzeichnis A in the Swiss controlled substances regulations. Medicinal use is permitted with appropriate authorization and licensing. |
| United Kingdom | Class A, Schedule 2 | Controlled under the Misuse of Drugs Act 1971. As a Class A substance, it carries the most severe penalties for unauthorized possession, sale, or distribution. Schedule 2 designation permits medical use under strict controls. |
| United States | Schedule II | Controlled under the Controlled Substances Act. Illegal to sell without a DEA license and illegal to buy or possess without a license or prescription. In 2017, the FDA requested Endo Pharmaceuticals to remove the extended-release formulation from the market due to concerns about opioid misuse and abuse associated with the injectable reformulation. |