Source: Υπουργείο Υγείας (CY) Revision Year: 2023 Publisher: Mundipharma Pharmaceuticals Ltd, 13, Othellos Street, Dhali Industrial Zone, 2540 Nicosia, Cyprus Tel.: +357 22815656 Fax: +357 22487833 Email: info@mundipharma.com.cy
Pharmacotherapeutic group: Natural opium alkaloids
ATC code: N02AA05
Oxycodone is a full opioid agonist with no antagonist properties. It has an affinity for kappa, mu and delta opiate receptors in the brain and spinal cord. Oxycodone is similar to morphine in its action. The therapeutic effect is mainly analgesic, anxiolytic and sedative.
See Section 4.4.
Overall, the safety data obtained with oxycodone in clinical, pharmacodynamic and pharmacokinetic studies demonstrate that oxycodone is generally well tolerated in paediatric patients with adverse events affecting mainly the gastrointestinal and nervous system. Adverse events were consistent with the known safety profile of oxycodone as well as of other comparable strong opioids (see section 4.8 Undesirable effects).
There are no clinical trial data on longer term use in children aged 12 to 18 years.
Mean peak plasma concentrations of approximately 20mg/ml were achieved within 1.5 hours of administration, median tmax values from both strengths of liquid being less than 1 hour.
A pharmacokinetic study in healthy volunteers has demonstrated that, following administration of a single 10 mg dose, OxyNorm liquid 5 mg/5 ml and OxyNorm concentrate 10 mg/ml provided an equivalent rate and extent of absorption of oxycodone.
Following absorption, oxycodone is distributed throughout the entire body. Approximately 45% is bound to plasma protein.
Oxycodone is metabolised in the liver via CYP3A4 and CYP2D6 to noroxycodone, oxymorphone and noroxymorphone, which are subsequently glucuronidated. Noroxycodone and noroxymorphone are the major circulating metabolites. Noroxycodone is a weak mu opioid agonist. Noroxymorphone is a potent mu opioid agonist; however, it does not cross the blood-brain barrier to a significant extent. Oxymorphone is a potent mu opioid agonist but is present at very low concentrations following oxycodone administration. None of these metabolites are thought to contribute significantly to the analgesic effect of oxycodone.
Oxycodone has an elimination half life of approximately 4.5 hours. The active drug and its metabolites are excreted in urine.
Studies involving controlled release oxycodone have demonstrated that the oral bioavailability of oxycodone is only slightly increased (16%) in the elderly. In patients with renal and hepatic impairment, the bioavailability of oxycodone was increased by 60% and 90%, respectively, and a reduced initial dose is recommended in these groups.
Oxycodone had no effect on fertility or early embryonic development in male and female rats at doses as high as 8 mg/kg/d. Also, oxycodone did not induce any deformities in rats at doses as high as 8 mg/kg/d or in rabbits at doses as high as 125 mg/kg/d. Dose-related increases in developmental variations (increased incidences of extra (27) presacral vertebrae and extra pairs of ribs) were observed in rabbits when the data for individual foetuses were analysed. However, when the same data were analysed using litters as opposed to individual foetuses, there was no dose-related increase in developmental variations although the incidence of extra presacral vertebrae remained significantly higher in the 125 mg/kg/d group compared to the control group. Since this dose level was associated with severe pharmacotoxic effects in the pregnant animals, the foetal findings may have been a secondary consequence of severe maternal toxicity.
In a prenatal and postnatal development study in rats, maternal body weight and food intake parameters were reduced for doses ≥ 2 mg/kg/d compared to the control group. Body weights were lower in the F1 generation from maternal rats in the 6 mg/kg/d dosing group. There were no effects on physical, reflexological, or sensory developmental parameters or on behavioural and reproductive indices in the F1 pups (the NOEL for F1 pups was 2 mg/kg/d based on body weight effects seen at 6 mg/kg/d). There were no effects on the F2 generation at any dose in the study.
The results of in-vitro and in-vivo studies indicate that the genotoxic risk of oxycodone to humans is minimal or absent at the systemic oxycodone concentrations that are achieved therapeutically.
Oxycodone was not genotoxic in a bacterial mutagenicity assay or in an in-vivo micronucleus assay in the mouse. Oxycodone produced a positive response in the in-vitro mouse lymphoma assay in the presence of rat liver S9 metabolic activation at dose levels greater than 25 μg/ml. Two in-vitro chromosomal aberrations assays with human lymphocytes were conducted. In the first assay, oxycodone was negative without metabolic activation but was positive with S9 metabolic activation at the 24 hour time point but not at other time points or at 48 hour after exposure. In the second assay, oxycodone did not show any clastogenicity either with or without metabolic activation at any concentration or time point
Carcinogenicity was evaluated in a 2-year oral gavage study conducted in Sprague-Dawley rats. Oxycodone did not increase the incidence of tumors in male and female rats at doses up to 6 mg/kg/day. The doses were limited by opioid-related pharmacological effects of oxycodone.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
