Oxycodon

DEA NFLIS-Drug Category -> Narcotic Analgesics

DEA Schedule II Controlled Substance

Pharmaceuticals -> Used in Switzerland

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds

Pharmaceuticals -> Opiates, opioids and metabolites

0.3

0.37

Rods from ethanol

Long rods from alcohol

166mg/mL

Insoluble in water

Nearly insoluble in water

Nearly insoluble in ether, potassium and sodium hydroxide

Soluble in ethanol, chloroform

5.59e+00 g/L

Breast Feeding; Lactation; Milk, Human; Analgesics, Opioid; Narcotics; Antitussive Agents; Opiates

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

Opioid analgesics

219 °C

MP: 218-220 °C

MP: 218-220 °C; Strongly refringent scales from alcohol; more soluble in alcohol than other form /Tautomeric oxycodone/

218 - 220 °C

8.53

pKa = 8.53

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P261, P263, P264, P270, P271, P280, P301+P317, P304+P340, P318, P319, P330, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 53 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

H302: Harmful if swallowed [Warning Acute toxicity, oral]

DEA schedule II controlled substance

Status: Active Update: 23-05-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/19669

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. ... Substances, vegetable origin or chemical synthesis. 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, naldemedine, nalmefene, naloxegol, naloxone, and naltrexone, and their respective salts, but including the following: Oxycodone (DEA Code Number: 9143) is included on this list.

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

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

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. /Oxycodone hydrochloride/

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. /Oxycodone hydrochloride/

Keep container tightly closed in a dry and well-ventilated place. /Oxycodone hydrochloride/

Oxycodone hydrochloride preparations should be stored in tight containers and generally should be protected from light and stored at 15-30 °C

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. /Oxycodone hydrochloride/

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.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product. /Oxycodone hydrochloride/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. Environmental precautions: Do not let product enter drains. /Oxycodone hydrochloride/

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection. /Oxycodone hydrochloride/

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday. /Oxycodone hydrochloride/

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. /Oxycodone hydrochloride/

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.

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Oxycodone hydrochloride/

Skin protection: Handle with gloves. /Oxycodone hydrochloride/

Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Oxycodone hydrochloride/

To treat Oxycodone overdose, primary attention should be given to the reestablishment of a patent airway and institution of assisted or controlled ventilation. Supportive measures (including oxygen and vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation. The narcotic antagonists, naloxone or nalmefene, are specific antidotes for opioid overdose. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to Oxycodone overdose. If needed the appropriate dose of naloxone hydrochloride or nalmefene should be administered simultaneously with efforts at respiratory resuscitation (see package insert for each drug for the details). Since the duration of action of oxycodone 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. Gastric emptying may be useful in removing unabsorbed drug. (L1712)

Strategies to reduce the misuse of mu opioid agonists are critically needed. Previous work has shown that kappa opioid agonists can diminish the abuse-related effects and augment the antinociceptive effects of mu agonists. However, use of traditional kappa agonists is limited by their dysphoric side effects. The current study examined the effects of nalfurafine, a clinically available atypical kappa agonist, on the reinforcing, thermal antinociceptive, and respiratory-depressant effects of oxycodone in male rats. To determine oxycodone/nalfurafine mixture proportions to be examined intravenously across procedures, a progressive ratio (PR) self-administration procedure compared the reinforcing effects of oxycodone (56 ug/kg/inj) available alone or as a mixture with co-administered nalfurafine (0.32, 1, or 3.2 ug/kg/inj), corresponding to oxycodone/nalfurafine proportions of 175:1, 56:1, and 18:1, respectively. Next, PR and thermal antinociception dose-effect functions were each determined for oxycodone, nalfurafine, and the same oxycodone/nalfurafine mixture proportions. Finally, the respiratory-depressant effects of equi-antinociceptive doses of oxycodone, nalfurafine, and the mixtures were compared. Nalfurafine decreased the reinforcing effects of oxycodone, and the 18:1 mixture did not function as a reinforcer. Oxycodone and nalfurafine each produced dose-dependent antinociception, and the mixtures produced additive antinociception. In addition, antinociceptive doses of the 56:1 and 18:1 mixtures did not produce respiratory depression. These results suggest that nalfurafine may augment the thermal antinociceptive effects while reducing the reinforcing and respiratory-depressant effects of oxycodone.

The Centers for Disease Control has declared opioid abuse to be an epidemic. Overdose deaths are largely assumed to be the result of excessive opioid consumption. In many of these cases, however, opioid abusers are often polydrug abusers. Benzodiazepines are one of the most commonly co-abused substances and pose a significant risk to opioid users. In 2016, the FDA required boxed warnings - the FDA's strongest warning - for prescription opioid analgesics and benzodiazepines about the serious risks associated with using these medications at the same time. The point of our studies was to evaluate the interactions between these two classes of drugs. We investigated whether diazepam adds to the depressant effects of opioids or do they alter the levels of tolerance to opioids. In the present study, we have found that the antinociceptive tolerance that developed to repeated administration of oxycodone was reversed by an acute dose of diazepam. Antinociceptive tolerance to hydrocodone was also reversed by acute injection of diazepam; however, a fourfold higher dose of diazepam was required when compared to reversal of oxycodone-induced tolerance. These doses of diazepam did not potentiate the acute antinociceptive effect of either opioid. The same dose of diazepam that reversed oxycodone antinociceptive tolerance also reversed oxycodone locomotor tolerance while having no potentiating effects. These studies show that diazepam does not potentiate the acute effect of prescription opioids but reverses the tolerance developed after chronic administration of the drugs.

Concomitant use of oxycodone with CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) may result in increased clearance and decreased plasma concentrations of oxycodone, with possible lack of efficacy or development of opiate withdrawal. Concomitant administration of oxycodone and the CYP3A4 inducer rifampin decreased AUC and peak plasma concentration of oxycodone by 86 and 63%, respectively. If concomitant therapy with a CYP3A4 inducer is discontinued, an increase in plasma oxycodone concentrations may occur, potentially increasing or prolonging therapeutic and adverse effects of the drug and increasing the risk of serious respiratory depression. Therefore, caution should be exercised and patients who require concomitant therapy with a CYP3A4 inhibitor or inducer, or who have recently discontinued such therapy, should be monitored closely at frequent intervals, and dosage adjustments should be considered until stable drug effects are achieved.

Because oxyocodone is metabolized by the cytochrome P-450 (CYP) microsomal enzyme system, principally by isoenzyme 3A4, concomitant use of oxycodone with drugs that inhibit CYP3A4 activity (e.g., macrolide antibiotics [e.g., erythromycin], azole antifungals [e.g., ketoconazole, voriconazole], protease inhibitors [e.g., ritonavir]) may result in reduced clearance and increased plasma concentrations of oxycodone, possibly resulting in increased or prolonged opiate effects, including an increased risk of fatal respiratory depression. These effects could be more pronounced with concomitant use of oxycodone and inhibitors of both CYP2D6 and CYP3A4, particularly when an inhibitor is added after a stable oxycodone dosage has been achieved. Concomitant administration of oxycodone hydrochloride (single 10-mg dose as extended-release tablets) and the potent CYP3A4 inhibitor ketoconazole (200 mg twice daily) increased area under the plasma concentration-time curve (AUC) and peak plasma concentration of oxycodone by 170 and 100%, respectively, while concomitant administration of voriconazole with oxycodone increased the AUC and peak plasma concentration of oxycodone by 3.6- and 1.7-fold, respectively. However, inhibition of the CYP2D6 pathway alone has not been shown to result in clinically important interactions. If concomitant therapy with a CYP3A4 inhibitor is discontinued, a decrease in plasma oxycodcone concentrations may occur, potentially decreasing analgesic efficacy or resulting in withdrawal effects.

For more Interactions (Complete) data for Oxycodone (16 total), please visit the HSDB record page.

Despite wide scale use for many decades, oxycodone has not been convincingly linked to instances of clinically apparent acute liver injury. However, oxycodone and other opioid-acetaminophen combinations have become a common cause of acute liver injury, which is usually the result of excessive use of the medication for the opioid effect, which leads secondarily and unintentionally to an overdose of acetaminophen. In 2014, the FDA warned against the use of opioid combinations in which the dose of acetaminophen is greater than 325 mg per tablet or unit dose. Because of their potential for hepatotoxicity, opioid combinations in which the dose of acetaminophen is greater than 325 mg per tablet or capsule were discontinued.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a structure estimation method(2), indicates that oxycodone is expected to have high mobility in soil(SRC). The pKa of oxycodone is 8.53(3), indicating that this compound will exist partially in 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 cation from moist soil is not expected because cations do not volatilize(SRC). Volatilization of neutral oxycodone from moist soil surfaces is not expected(SRC) given an estimated Henry's Law constant of 2.3X10-16 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Oxycodone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.3X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2017).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a structure estimation method(2), indicates that oxycodone is not expected to adsorb to suspended solids and sediment(SRC). A pKa of 8.53(3) indicates oxycodone will exist partially in the cation form at pH values of 5 to 9 and, therefore, volatilization of the cation from water surfaces is not expected to be an important fate process(SRC). Volatilization of neutral oxycodone from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 2.3X10-16 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Oxycodone is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(4). According to a classification scheme(4), an estimated BCF of 3(SRC), from an estimated log Kow of 0.66(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low. Biodegradation data in water were not available(SRC, 2017).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), oxycodone, which has an estimated vapor pressure of 2.3X10-10 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 oxycodone may be removed from the air by wet and dry deposition(SRC). Oxycodone does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

Oxycodone has the potential for addiction and is classified as a controlled substance. The adverse effect profile of oxycodone is similar to that of other opioid medications. Constipation is the most common overall adverse effect. The intensity of these adverse effects tends to decrease over time.

IDENTIFICATION AND USE: Oxycodone is a Schedule II controlled substance. It is an opioid agonist indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. HUMAN STUDIES: Oxycodone is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Acute overdose can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations. Both tolerance and physical dependence can develop during chronic opioid therapy. Prolonged use during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening. Accidental ingestion of even one dose especially by children, can result in respiratory depression and death due to an overdose of oxycodone. ANIMAL STUDIES: In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of oxycodone administered during the period of organogenesis up to 16 mg/kg/day and 25 mg/kg/day, respectively. These studies revealed no evidence of teratogenicity or embryo-fetal toxicity due to oxycodone. Exposure to 0.5 mg/kg/day oxycodone in utero was associated with hyperactivity in adult rats in an open field. No significant effects of perinatal oxycodone exposure were detected on isolation-induced ultrasonic vocalizations in the early postnatal period or on learning and memory in the water maze in adult offspring. Offspring of pregnant rats administered oxycodone during gestation have been reported to exhibit neurobehavioral effects including altered stress responses, increased anxiety-like behavior. Oxycodone was genotoxic in an in vitro mouse lymphoma assay in the presence of metabolic activation. There was no evidence of genotoxic potential in an in vitro bacterial reverse mutation assay (Salmonella typhimurium and Escherichia coli) and in an assay for chromosomal aberrations (in vivo mouse bone marrow micronucleus assay).

Signs and Symptoms of Overdose

Oxycodone acts as a weak agonist at mu, kappa, and delta opioid receptors within the central nervous system (CNS). Oxycodone primarily affects mu-type opioid receptors, which are coupled with G-protein receptors and function as modulators, both positive and negative, of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is inhibited. Opioids such as oxycodone also inhibit the release of vasopressin, somatostatin, insulin, and glucagon. Opioids close N-type voltage-operated calcium channels (kappa-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (mu and delta receptor agonist). This results in hyperpolarization and reduced neuronal excitability.

/AQUATIC SPECIES/ Pharmaceuticals are present in low concentrations (<100 ng/L) in most municipal wastewater effluents but may be elevated locally because of factors such as input from pharmaceutical formulation facilities. Using existing concentration data, the authors assessed pharmaceuticals in laboratory exposures of fathead minnows (Pimephales promelas) and added environmental complexity through effluent exposures. In the laboratory, larval and mature minnows were exposed to a simple opioid mixture (hydrocodone, methadone, and oxycodone), an opioid agonist (tramadol), a muscle relaxant (methocarbamol), a simple antidepressant mixture (fluoxetine, paroxetine, venlafaxine), a sleep aid (temazepam), or a complex mixture of all compounds. Larval minnow response to effluent exposure was not consistent. The 2010 exposures resulted in shorter exposed minnow larvae, whereas the larvae exposed in 2012 exhibited altered escape behavior. Mature minnows exhibited altered hepatosomatic indices, with the strongest effects in females and in mixture exposures. In addition, laboratory-exposed, mature male minnows exposed to all pharmaceuticals (except the selective serotonin reuptake inhibitor mixture) defended nest sites less rigorously than fish in the control group. Tramadol or antidepressant mixture exposure resulted in increased splenic T lymphocytes. Only male minnows exposed to whole effluent responded with increased plasma vitellogenin concentrations. Female minnows exposed to pharmaceuticals (except the opioid mixture) had larger livers, likely as a compensatory result of greater prominence of vacuoles in liver hepatocytes. The observed alteration of apical endpoints central to sustaining fish populations confirms that effluents containing waste streams from pharmaceutical formulation facilities can adversely impact fish populations but that the effects may not be temporally consistent. The present study highlights the importance of including diverse biological endpoints spanning levels of biological organization and life stages when assessing contaminant interactions.

Oxycodone was detected in 56% of effluent collected 2006-2009 from 23 wastewater treatment plants located in 12 states across the US at 0.31-0.73 ug/L(1). Oxycodone was detected in 75, 91 and 100% of samples collected 2004-2009 from three wastewater treatment plants in New York, the highest concentration detected was 1700 ug/L(1). In west Prong Little Pigeon River, TN, oxycodone was not detected (detection limit 0.375 ug/L) at the outfall of two waste water treatment plants(2). The average oxycodone concentration was reported as 15-220 ng/L in influent samples collected from 7 wastewater treatment plants located in the US(3). Influent and effluent samples collected from wastewater treatment plants in the UK contained oxycodone at 5-12 and 7-12 ng/L, respectively(4). Oxycodone was detected in 2 of 11 influent samples at <0.020-0.07 and was not detected (detection limit 0.010 ug/L) in effluent samples collected March 2005 from 12 sewage treatment plants on the Rhine River in Germany(5).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of oxycodone can be estimated to be 80(SRC). According to a classification scheme(2), this estimated Koc value suggests that oxycodone is expected to have high mobility in soil. The pKa of oxycodone is 8.53(3), indicating that this compound will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

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. ... Substances, vegetable origin or chemical synthesis. 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, naldemedine, nalmefene, naloxegol, naloxone, and naltrexone, and their respective salts, but including the following: Oxycodone (DEA Code Number: 9143) is included on this list.

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

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

N02AA05

N - Nervous system

QN - Nervous system

Oxycodone acts directly on a number of tissues not related to its analgesic effect. These tissues include the respiratory centre in the brain stem, the cough centre in the medulla, muscles of the pupils, gastrointestinal tract, cardiovascular system, endocrine system, and immune system. Oxycodone's effect on the respiratory centre is dose dependant respiratory depression. The action on the cough centre is suppression of the cough reflex. Pupils become miopic or decrease in size, peristalsis of the gastrointestinal tract slows, and muscle tone in the colon may increase causing constipation. In the cardiovascular system histamine may be released leading to pruritis, red eyes, flushing, sweating, and decreased blood pressure. Endocrine effects may include increased prolactin, decreased cortisol, and decreased testosterone. It is not yet known if the effects of opioids on the immune system are clinically significant.

The full mechanism of oxycodone is not known. Under conditions of inflammation or hyperalgesia, opioid receptors in the heart, lungs, liver, gastrointestinal tract, and reproductive system are upregulated and transported to nerve terminals. Oxycodone and its active metabolites, noroxycodone, oxymorphone, and noroxymorphone are opioid agonists. These compounds passively diffuse across the blood brain barrier or may be actively transported across by an unknown mechanism. Oxycodone and its active metabolites can selectively bind to the mu opioid receptor, but also the kappa and delta opioid receptors in the central nervous system and periphery, and induce a G protein coupled receptor signalling pathway. Activation of mu opioid receptors inhibits N-type voltage operated calcium channels, inhibiting responses to pain.

Oxycodone is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with oxycodone. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.

... Oxycodone has the same mechanism of action as other opioids: binding to a receptor, inhibition of adenylyl-cyclase and hyperpolarization of neurons, and decreased excitability. These mechanisms also play a part in the onset of dependence and tolerance. ...

The apparent elimination half life of oxycodone is 3.2 hours for immediate release formulations and 4.5 hours for extended release formulations. Noroxycodone has a half life of 5.8 hours, oxymorphone has a half life of 8.8 hours, noroxymorphone has a half life of 9 hours.

This study aimed to characterize the pharmacokinetics of oxycodone and its major metabolites in infants and covered the age range between extremely preterm neonates and 2-year-old infants. Seventy-nine infants (gestational age 23-42 weeks; postnatal age 0-650 days) received intravenous oxycodone hydrochloride trihydrate at a dose of 0.1 mg/kg during or after surgery. ... In extremely preterm neonates (n = 6) median of elimination half-life was 8.8 hr (range 6.8-12.5), in preterm (n = 11) 7.4 hr (4.2-11.6), and in older neonates (n = 22) 4.1 hr (2.4-5.8), all of which were significantly longer than that in infants aged 6-24 months (n = 12) 2.0 hr (1.7-2.6). ...

The apparent elimination half-life following oral administration of the extended-release tablets or conventional preparations is 4.5 or 3.2 hours, respectively.

The apparent elimination half-life following oral administration of the extended-release capsules under fed conditions is 5.6 hours, compared with 3.2 hours following administration of conventional preparations of the drug.

The apparent elimination half-life of oxycodone following oral administration of the fixed-combination extended-release tablets is 4.5 hours, compared with 3.9 hours following administration of conventional preparations of the drug.

For more Biological Half-Life (Complete) data for Oxycodone (6 total), please visit the HSDB record page.

Oxycodone's hepatic metabolism is extensive and completed by 4 main reactions. CYP3A4 and 3A5 perform N-demethylation, CYP2D6 performs O-demethylation, unknown enzymes perform 6-keto-reduction, and unknown enzymes perform conjugation. Oxycodone is metabolized by CYP3A4 and CYP3A5 to noroxycodone and then by CYP2D6 to noroxymorphone. Noroxycodone and noroxymorphone are the primary circulating metabolites. Noroxycodone can also be 6-keto-reduced to alpha or beta noroxycodol. Oxycodone can be metabolized by CYP2D6 to oxymorphone and then by CYP3A4 to noroxymorphone. Oxymorphone can also be 6-keto-reduced to alpha or beta oxymorphol. Oxycodone can also be 6-keto-reduced to alpha and beta oxycodol. The active metabolites noroxycodone, oxymorphone, and noroxymorphone can all be conjugated before elimination.

The hepatic metabolism of oxycodone by cytochromes P450 (CYP) and the UDP-glucuronosyltransferases (UGT), the main metabolic enzymes of phase I and phase II, respectively, was assessed in vitro. The N-demethylation by CYP3A4/5 and the O-demethylation by CYP2D6 in human liver microsomes (HLM) followed Michaelis-Menten kinetics, with intrinsic clearances of 1.46 uL/min/mg and 0.35 uL/min/mg, respectively. Although noroxycodone and oxymorphone mainly contribute to the elimination of oxycodone, the simulated total in vivo clearance using in vitro phase I metabolism was underestimated. For the first time, metabolism of oxycodone by UGT was deeply investigated using HLM, recombinant enzymes and selective inhibitors. Oxycodone-glucuronide was mainly produced by UGT2B7 (Km=762 +/- 153 uM, Vmax=344 +/- 20 peak area/min/mg) and to a lesser extent by UGT2B4 (Km=2454 +/- 497 uM, Vmax=201 +/- 19 peak area/min/mg). Finally, the kinetics of the drug-drug interactions were assessed using two CYP and UGT cocktail approaches. Incubations of HLM with phase I and phase II drug probes showed that oxycodone mainly decreased the in vitro activities of CYP2D6, CYP3A4/5, UGT1A3, UGT1A6 and UGT2B subfamily with an important impact on UGT2B7.

Oxycodone hydrochloride is extensively metabolized by multiple metabolic pathways to noroxycodone, oxymorphone, and noroxymorphone, which are subsequently glucuronidated. CYP3A4 mediated N-demethylation to noroxycodone is the primary metabolic pathway of oxycodone with less contribution from CYP2D6 mediated O-demethylation to oxymorphone. Therefore, the formation of these and related metabolites can, in theory, be affected by other drugs. The major circulating metabolite is noroxycodone with an AUC ratio of 0.6 relative to that of oxycodone. Noroxycodone is reported to be a considerably weaker analgesic than oxycodone. Oxymorphone, although possessing analgesic activity, is present in the plasma only in low concentrations. The correlation between oxymorphone concentrations and opioid effects was much less than that seen with oxycodone plasma concentrations. The analgesic activity profile of other metabolites is not known.

... The two main metabolites /of oxycodone/ are oxymorphone-which is also a very potent analgesic-and noroxycodone, a weak analgesic. ...

Oxycodone undergoes N-demethylation to noroxycodone and O-demethylation to oxymorphone. The cytochrome P450 (P450) isoforms capable of mediating the oxidation of oxycodone to oxymorphone and noroxycodone were identified using a panel of recombinant human P450s. CYP3A4 and CYP3A5 displayed the highest activity for oxycodone N-demethylation; intrinsic clearance for CYP3A5 was slightly higher than that for CYP3A4. CYP2D6 had the highest activity for O-demethylation. Multienzyme, Michaelis-Menten kinetics were observed for both oxidative reactions in microsomes prepared from five human livers. Inhibition with ketoconazole showed that CYP3A is the high affinity enzyme for oxycodone N-demethylation; ketoconazole inhibited >90% of noroxycodone formation at low substrate concentrations. CYP3A-mediated noroxycodone formation exhibited a mean K(m) of 600 +/- 119 uM and a V(max) that ranged from 716 to 14523 pmol/mg/min. Contribution from the low affinity enzyme(s) did not exceed 8% of total intrinsic clearance for N-demethylation. Quinidine inhibition showed that CYP2D6 is the high affinity enzyme for O-demethylation with a mean K(m) of 130 +/- 33 uM and a V(max) that ranged from 89 to 356 pmol/mg/min. Activity of the low affinity enzyme(s) accounted for 10 to 26% of total intrinsic clearance for O-demethylation. On average, the total intrinsic clearance for noroxycodone formation was 8 times greater than that for oxymorphone formation across the five liver microsomal preparations (10.5 uL/min/mg versus 1.5 uL/min/mg). Experiments with human intestinal mucosal microsomes indicated lower N-demethylation activity (20-50%) compared with liver microsomes and negligible O-demethylation activity, which predict a minimal contribution of intestinal mucosa in the first-pass oxidative metabolism of oxycodone.

Oxycodone has known human metabolites that include noroxycodone and oxymorphone.

CD35PMG570

OXYCODONE

Mechanisms of Action [MoA] - Full Opioid Agonists

Established Pharmacologic Class [EPC] - Opioid Agonist

Oxycodone is an Opioid Agonist. The mechanism of action of oxycodone is as a Full Opioid Agonist.

OXYCODONE

Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.

Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS.

Oxycodone has an oral bioavailability of 60% to 87% that is unaffected by food. The area under the curve is 135ng/mL\*hr, maximum plasma concentration is 11.5ng/mL, and time to maximum concentration is 5.11hr in patients given a 10mg oral immediate release dose of oxycodone.

Oxycodone and its metabolites are eliminated in the urine. Unbound noroxycodone makes up 23% of the dose recovered in urine and oxymorphone makes up <1%. Conjugated oxymorphone makes up 10% of the recovered dose. Free and conjugated oxycodone makes up 8.9% of the recovered dose, noroxymorphone makes up 14%, and reduced metabolites make up 18%.

2.6L/kg.

Total plasma clearance is 1.4L/min in adults.

About 60 to 87% of an oral dose reaches the systemic circulation in comparison to a parenteral dose. This high oral bioavailability (compared to other opioids) is due to lower pre-systemic and/or first-pass metabolism of oxycodone.

The oral bioavailability of oxycodone is 60-87%. The relative oral bioavailability of extended-release tablets of oxycodone hydrochloride compared with conventional oral preparations is 100%. The extended-release tablets are formulated to provide controlled delivery of oxycodone over 12 hours. Release of the drug from the extended-release tablets is pH independent. Following rectal administration of oxycodone hydrochloride extended-release tablets in healthy adults, the area under the plasma concentration-time curve (AUC) and peak plasma concentration were increased by 39 and 9%, respectively, compared with oral administration. With multiple oral dosing, steady-state plasma concentrations usually are achieved within 24-36 hours in healthy individuals receiving extended-release tablets of oxycodone hydrochloride. Administration of the extended-release tablets with food does not substantially affect the extent of absorption.

Oxycodone (DEA Code Number: 9143) 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.

Narcotics; Analgesics, Opioid

MEDICATION

Use (kg; approx.) in Germany (2009): >1000

For the treatment of diarrhoea, pulmonary oedema and for the relief of moderate to moderately severe pain.

4,5alpha-epoxy-3,14-dihydroxy-17-methylmorphinan-6-one (oxymorphone); 4,5alpha-epoxy-3-methoxy-17-methylmorphinan-6alpha,14-diol (7,8-dihydro-14-hydroxycodeine); 4,5alpha-epoxy-14-hydroxy-3-methoxymorphinan-6-one (noroxycodone); 7,8-didehydro-4,5alpha-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one (14-hydroxycodeinone); 4,5alpha-epoxy-3-methoxy-17-methylmorphinan-6-one (hydrocodone); 6,7,8,14-tetrahydro-4,5alpha-epoxy-3,6-dimethoxy-17-methylmorphinan (thebain) /Oxycodone Hydrochloride/

Thebaine is oxidized with hydrogene peroxide to 14-hydroxycodeinone, which is hydrogenated directly or via its oxime, or its bromination products to oxycodone. The reduction of 14-hydroxycodeinone can also be performed with sodium hydrosulfite. Alternatively, 14-hydroxycodeinone is prepared by oxidation of codeine.

Table: Oxycodone Hydrochloride Preparations [Table#4469]

Table: Oxycodone and Acetaminophen Preparations [Table#4470]

Table: Oxycodone and Aspirin Preparations [Table#4471]

Oral: Tablets, film-coated: 5 mg with Ibuprofen 400 mg Generic Name: Oxycodone Hydrochloride and Ibuprofen Film-coated Tablets (C-II)

For more Formulations/Preparations (Complete) data for Oxycodone (7 total), please visit the HSDB record page.