Oxymorphon

As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and materials.

Store in tight container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity.

Store at 25 °C (77 °F); excursions permitted to 15-30 °C (59-86 °F).

Wear approved respiratory protection, chemically compatible gloves, and protective clothing. Wipe up spillage or collect spillage using a high-efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

As a general rule, when handling USP Reference Standards, avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.

As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. The completeness of the cleaning procedures should be considered before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at the end of shift, but should remain at employee's place of work for cleaning.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Respiratory Protection: Where respirators are deemed necessary to reduce or control occupational exposures, use NIOSH-approved respiratory protection and have an effective respirator program in place. Gloves: Chemically compatible. For handling solutions, ensure that the glove material is protective against the solvent being used. Use handling practices that minimize direct hand contact. Employees who are sensitive to natural rubber (latex) should use nitrile or other synthetic nonlatex gloves. Use of powdered latex gloves should be avoided due to the risk of latex allergy. Eye Protection: Safety glasses with sideshields are recommended. Face shields or goggles may be required if splash potential exists or if corrosive materials are present. Approved eye protection (e.g., bearing the ANSI Z87 or CSA stamp) is preferred. Maintain eyewash facilities in the work area. Protective clothing: For handling of laboratory scale quantities, a cloth lab coat is recommended. Where significant quantities are handled, work clothing may be necessary to prevent take-home contamination.

Airborne exposure should be controlled primarily by engineering controls such as general dilution ventilation, local exhaust ventilation, or process enclosure. Local exhaust ventilation is generally preferred to general exhaust because it can control the contaminant at its source, preventing dispersion into the work area. An industrial hygiene survey involving air monitoring may be used to determine the effectiveness of engineering controls. Effectiveness of engineering controls intended for use with highly potent materials should be assessed by use of nontoxic surrogate materials. Avoid any open handling of this material, particularly for grinding, crushing, weighing, or other dust-generating or aerosol-generating procedures. Use a laboratory fume hood, vented enclosure, glovebox, or other effective containment.

... Blood concentrations were 0.05 mg/L (50 ug/L) and 0.12 mg/L (120 ug/L). /fatal/

The mean concentration for oxymorphone in postmortem central (n = 28) and peripheral (n = 23) blood samples was 0.15 mg/L. The median values for the central and peripheral samples were 0.10 mg/L (range: 0.011-0.59) and 0.075 mg/L (range: 0.017-0.82), respectively. Liver concentrations ranged from "none detected" to > 2.0 mg/kg, with mean and median values of 0.36 and 0.30 mg/kg, respectively. The majority of urine samples were > 0.50 mg/L. /fatal/

Toxicology on the deceased female revealed the presence of 0.13 mg/L oxymorphone ... in her blood. Gastric contents contained 0.25 mg/L of oxymorphone ... /fatal/

Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The opioid antagonist naloxone hydrochloride is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to opioids including oxymorphone. Therefore, an appropriate dose of naloxone hydrochloride should be administered (usual initial adult dose 0.4 mg-2 mg) preferably by the intravenous route and simultaneously with efforts at respiratory resuscitation. Since the duration of action of oxymorphone may exceed that of the antagonist, the patient should be kept under continued surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. Naloxone hydrochloride should not be administered in the absence of clinically significant respiratory or cardiovascular depression. In addition, it should be considered that the use of an opioid antagonist in patients physically dependent on opioids may precipitate an acute withdrawal syndrome that cannot be readily suppressed while the action of the antagonist persists. If respiratory depression is associated with muscular rigidity, administration of a neuromuscular blocking agent may be necessary to facilitate assisted or controlled ventilation. Muscular rigidity may also respond to opioid antagonist therapy. Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated. (L1712)

Oxymorphone may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression because respiratory depression, hypotension, and profound sedation or coma may result.

Patients receiving other opioid analgesics, general anesthetics, phenothiazines, other tranquilizers, sedatives, hypnotics, or other CNS depressants (including alcohol) concomitantly with oxymorphone may exhibit an additive CNS depression. Interactive effects resulting in respiratory depression, hypotension, profound sedation, or coma may result if these drugs are taken in combination with the usual dose of oxymorphone injection.

Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol, and buprenorphine) should be administered with caution to a patient who has received or is receiving a course of therapy with a pure opioid agonist analgesic such as oxymorphone. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of oxymorphone and/or may precipitate withdrawal symptoms in these patients.

No specific interaction between oxymorphone and monoamine oxidase inhibitors has been observed, but caution in the use of any opioid in patients taking this class of drugs is appropriate.

For more Interactions (Complete) data for Oxymorphone (11 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 160(SRC), determined from a structure estimation method(2), indicates that oxymorphone is expected to have moderate mobility in soil(SRC). The pKa of oxymorphone is 8.17(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the neutral species from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.1X10-19 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Oxymorphone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.6X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(6). Biodegradation data in soil were not available(SRC, 2012).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 160(SRC), determined from a structure estimation method(2), indicates that oxymorphone is expected to adsorb to suspended solids and sediment(SRC). Volatilization of the neutral species from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 4.1X10-19 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). A pKa of 8.17(5) indicates oxymorphone will exist partially in the cation form at pH values of 5 to 9, and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow of 0.83(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2012).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), oxymorphone, which has an estimated vapor pressure of 4.6X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase oxymorphone may be removed from the air by wet or dry deposition(SRC). Oxymorphone does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

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.

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.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of oxymorphone can be estimated to be 160(SRC). According to a classification scheme(2), this estimated Koc value suggests that oxymorphone is expected to have moderate mobility in soil. The pKa of oxymorphone is 8.17(3), indicating that this compound will exist partially in the cation in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/SIGNS AND SYMPTOMS/ Acute overdosage with oxymorphone injection is characterized by respiratory depression, (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur. Oxymorphone injection may cause miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

/CASE REPORTS/ ... To date, there are very few reported values for postmortem concentrations of oxymorphone in the literature to aid in the interpretation of these cases. /Investigators/ report 33 medical examiner cases involving oxymorphone and provide the distribution of oxymorphone in postmortem blood, liver, and urine samples. Oxymorphone was detected in blood by enzyme immunoassay and confirmed by gas chromatography- mass spectrometry utilizing a solid-phase extraction procedure. Calibration curves from 0.025 to 0.50 mg/L were established with a limit of quantitation of 0.025 mg/L. The mean concentration for oxymorphone in postmortem central (n = 28) and peripheral (n = 23) blood samples was 0.15 mg/L. The median values for the central and peripheral samples were 0.10 mg/L (range: 0.011-0.59) and 0.075 mg/L (range: 0.017-0.82), respectively. Liver concentrations ranged from "none detected" to > 2.0 mg/kg, with mean and median values of 0.36 and 0.30 mg/kg, respectively. The majority of urine samples were > 0.50 mg/L.

/CASE REPORTS/ There has been an increased awareness of illicit opiate abusers using the narcotic oxymorphone (Opana) by inhalation. Many laboratory screening techniques currently in use cannot detect oxymorphone in blood or urine. Consequently, biological specimens containing low to moderate concentrations of oxymorphone will likely go undetected. The circumstances, pathology findings, and toxicology results of two fatalities involving oxymorphone are presented. An opiate confirmation gas chromatography-mass spectrometry (GC-MS) procedure, described in detail was able to detect, confirm, and quantify oxymorphone in both subjects. The blood concentrations were 0.05 mg/L (50 ug/L) and 0.12 mg/L (120 ug/L).

/CASE REPORTS/ Two cases are reported involving the abuse of extended-release oxymorphone hydrochloride tablets (Opana ER) in combination with alprazolam (Xanax). Two juvenile females were discovered unresponsive and hypoxic by a male acquaintance. The trio had reportedly crushed and snorted Opana ER tablets and consumed Xanax for recreational purposes. Emergency personnel were able to stabilize one female. The second female was pronounced dead at the scene. Blood and urine samples from the surviving female were collected at the trauma center between 48 and 96 hr post incident. Toxicology results showed the presence of oxymorphone, doxylamine, dextromethorphan, alprazolam, alpha-hydroxyalprazolam, oxazepam, and temazepam in her urine. No drugs were detected in her blood. Toxicology on the deceased female revealed the presence of 0.13 mg/L oxymorphone and 0.04 mg/L alprazolam in her blood. Gastric contents contained 0.25 and 0.93 mg/L of oxymorphone and alprazolam, respectively. Oxymorphone, alprazolam, and alpha-hydroxyalprazolam were present in her urine. Quantitative results were achieved by gas chromatography-mass spectrometry monitoring selected ions for the oxime-oxymorphone-trimethylsilyl derivative, alprazolam, and the alpha-hydroxyalprazolam tert-butyldimethylsilyl derivative. The established linearity ranges for the opiate and benzodiazepine methods were 0.050-3.000 and 0.025-1.000 mg/L, respectively. The cause of death was reported as multiple drug toxicity, and the manner of death was accidental.

Oxymorphone hydrochloride injection. ... The drug is a narcotic analgesic, preanesthetic, anesthetic, and substitute anesthetic adjuvant for intramuscular, subcutaneous or intravenous administration to cats and dogs.

Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. Unless specifically excepted or unless listed in another schedule, any of the following substances whether produced directly or indirectly by extraction from substances of vegetable origin, or independently by means of chemical synthesis, or by a combination of extraction and chemical synthesis: (1) Opium and opiate, and any salt, compound, derivative, or preparation of opium or opiate excluding apomorphine, thebaine-derived butorphanol, dextrorphan, nalbuphine, nalmefene, naloxone, and naltrexone, and their respective salts, but including the following. Oxymorphone (DEA Code Number: 9652) is included on this list.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including oxymorphone hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Oxymorphone hydrochloroide/

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Oxymorphone hydrochloride is included on this list. /Oxymorphone hydrochloride/

Oxymorphone is a Schedule II controlled substance.

Schedule II Controlled Substance: (A) The drug or other substance has a high potential for abuse; (B) The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions; and (C) Abuse of the drug or other substances may lead to severe psychological or physical dependence.

MEDICATION

MEDICATION (VET)

For the treatment of moderate-to-severe pain.

Oxycodone is hydrolyzed with boiling concentrated hydrobromic acid.

Thebaine is dissolved in aqueous formic acid and treated with 30% hydrogen peroxide, after which neutralization with aqueous ammonia yields 14-hydroxycodeinone. This then is dissolved in acetic acid and hydrogenated with the aid of palladium-charcoal catalyst to form 14-hydroxy-7,8-dihydrocodeinone (oxycodone). In the form of its hydrochloride, this compound is demethylated by means of heating with pyridine hydrochloride to yield crude oxymorphone hydrochloride, which is then purified. /Oxymorphone hydrochloride/

Street Names: Blue Heaven, Blues, Mrs. O, New Blues, Octagons, Oranges, Orgasna IR, OM, Pink, Pink Heaven, Pink Lady, Pink O, Stop Signs, and The O Bomb.

Table: Oxymorphone Hydrochloride Preparations [Table#8046]