Boxed Warnings
Limitations of use. Because of the risks associated with the use of opioids, OxyNorm solution for injection or infusion should only be used in patients for whom other treatment options, including non-opioid analgesics, are ineffective, not tolerated or otherwise inadequate to provide appropriate management of pain (see Section 4.4 Special Warnings and Precautions for Use).
Hazardous and harmful use. OxyNorm solution for injection or infusion poses risks of hazardous and harmful use which can lead to overdose and death. Assess the patient's risk of hazardous and harmful use before prescribing and monitor the patient regularly during treatment (see Section 4.4 Special Warnings and Precautions for Use).
Life threatening respiratory depression. Serious, life-threatening or fatal respiratory depression may occur with the use of OxyNorm solution for injection or infusion. Be aware of situations which increase the risk of respiratory depression, modify dosing in patients at risk and monitor patients closely, especially on initiation or following a dose increase (see Section 4.4 Special Warnings and Precautions for Use).
Concomitant use of benzodiazepines and other central nervous system (CNS) depressants, including alcohol. Concomitant use of opioids with benzodiazepines, gabapentinoids, antihistamines, tricyclic antidepressants, antipsychotics, cannabis or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Limit dosages and durations to the minimum required; and monitor patients for signs and symptoms of respiratory depression and sedation. Caution patients not to drink alcohol while taking OxyNorm solution for injection or infusion.
1 Name of Medicine
Oxycodone hydrochloride.
2 Qualitative and Quantitative Composition
The 10 mg/1 mL solution for injection contains 10 mg oxycodone hydrochloride.
The 20 mg/2 mL solution for injection contains 20 mg oxycodone hydrochloride.
The 200 mg/20 mL solution for injection contains 200 mg oxycodone hydrochloride.
The 50 mg/1 mL solution for injection contains 50 mg oxycodone hydrochloride.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
The 10 mg/1 mL, 20 mg/2 mL and 200 mg/20 mL solutions for injection are clear, colourless solutions, practically free from particulates.
The 50 mg/1 mL solution for injection is a clear, colourless to pale yellow solution, practically free from particulates.
4 Clinical Particulars
4.9 Overdose
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
Symptoms. Acute overdosage with oxycodone can be manifested by respiratory depression (reduced respiratory rate and/or tidal volume, cyanosis), extreme somnolence progressing to stupor or coma, hypotonia, miosis (dilated if hypoxia is severe), cold and/or clammy skin and sometimes bradycardia, hypoglycemia, hypotension, pulmonary oedema, and death. Severe overdose may result in apnoea, pulmonary oedema, circulatory collapse and death. Toxic leukoencephalopathy has been observed with oxycodone overdose.
Treatment of oxycodone overdosage. Primary attention should be given to immediate supportive therapy with the establishment of adequate respiratory exchange through the provision of a patent airway and institution of assisted or controlled ventilation. Adequate body temperature and fluid balance should be maintained. Oxygen, intravenous fluids, vasopressors and other supportive measures should be used as indicated to manage the circulatory shock accompanying an overdose. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation.
If there are signs of clinically significant respiratory or cardiovascular depression, the use of an opioid antagonist should be considered. The opioid antagonist naloxone hydrochloride is a specific antidote against respiratory depression due to overdosage. Concomitant efforts at respiratory resuscitation should be carried out. The patient should be under continued surveillance and doses of the antagonist should be repeated as needed to maintain adequate respiration.
For massive overdosage, associated with clinically significant respiratory or cardiovascular depression, 0.8 mg naloxone may be administered intravenously, repeating at 2-3 minute intervals as necessary, or by a titrated infusion of 2 mg in 500 mL of normal saline or 5% dextrose (0.004 mg/mL). The infusion should be run at a rate related to previous bolus doses administered and should be in accordance with the patient's response. However, because the duration of action of naloxone is relatively short, the patient must be carefully monitored until spontaneous respiration is reliably re-established. Monitoring for a further 24-48 hours is then recommended in case of possible relapse. Please see naloxone hydrochloride injection product information for further information.
In an individual physically dependent on or tolerant to opioids, the administration of the usual dose of opioid antagonist will precipitate an acute withdrawal syndrome. The severity of this syndrome will depend on the degree of physical dependence and the dose of antagonist administered. The use of opioid antagonists in such individuals should be avoided if possible. If an opioid antagonist must be used to treat serious respiratory depression in the physically dependent patient, the antagonist should be administered with extreme care by using dosage titration, commencing with 10 to 20% of the usual recommended initial dose.
Toxicity. Oxycodone toxicity may result from overdosage but because of the great interindividual variation in sensitivity to opioids it is difficult to determine an exact dose of any opioid that is toxic or lethal. The toxic effects and signs of overdosage may be less pronounced than expected, when pain and/or tolerance are manifest.
5 Pharmacological Properties
5.3 Preclinical Safety Data
Genotoxicity. Oxycodone was not genotoxic in bacterial gene mutation assays, but was positive in the mouse lymphoma assay. In assays of chromosomal damage, genotoxic effects occurred in the human lymphocyte chromosomal assay in vitro, but not in the in vivo bone marrow micronucleus assay in mice.
Carcinogenicity. Carcinogenicity was evaluated in a 2-year oral gavage study conducted in Sprague-Dawley rats. Oxycodone did not increase the incidence of tumours in male and female rats at doses up to 6 mg/kg/day (equivalent to 6.8 mg/day in men and 24.6 mg/day in women, based on estimated AUC values). The doses were limited by opioid-related pharmacological effects of oxycodone.
6 Pharmaceutical Particulars
6.7 Physicochemical Properties
Oxycodone hydrochloride is a white, crystalline, odourless powder freely soluble in water, sparingly soluble in ethanol and nearly insoluble in ether.
Chemical name. 4,5α-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride.
Molecular formula. C18H21NO4.
Molecular weight. 351.83.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSOXYHYD.gif CAS number. 124-90-3.
7 Medicine Schedule (Poisons Standard)
S8.
Summary Table of Changes
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/OXYNINST.gif
