Boxed Warnings
Limitations of use. Because of the risks associated with the use of opioids, OxyNorm 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 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. 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.
1 Name of Medicine
Oxycodone hydrochloride.
2 Qualitative and Quantitative Composition
OxyNorm 5 mg capsules contains 5 mg of oxycodone hydrochloride.
OxyNorm 10 mg capsules contains 10 mg of oxycodone hydrochloride.
OxyNorm 20 mg capsules contains 20 mg of oxycodone hydrochloride.
OxyNorm Oral liquid contains 1 mg/mL of oxycodone hydrochloride.
Excipients with known effect. Benzoates, saccharin.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
5 mg capsules are size 4 orange/beige opaque capsules printed with ONR and 5 in black ink.
10 mg capsules are size 4 white/beige opaque capsules printed with ONR and 10 in black ink.
20 mg capsules are size 4 pink/beige opaque capsules printed with ONR and 20 on black ink.
The oral liquid is a clear to straw coloured solution.
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, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, hypotonia, cold and/or clammy skin, miosis (dilated if hypoxia is severe), and sometimes bradycardia, hypoglycemia, hypotension, pulmonary oedema, and death.
Toxic leukoencephalopathy has been observed with oxycodone overdose. Severe overdose may result in apnoea, pulmonary oedema, circulatory collapse and death.
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.
Activated charcoal may reduce absorption of the drug if given within one or two hours after ingestion. Administration of activated charcoal should be restricted to patients who are fully conscious with an intact gag reflex or protected airway. A saline cathartic or sorbitol added to the first dose of activated charcoal may speed gastrointestinal passage of the product. In patients who are not fully conscious or have an impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected.
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 for respiratory depression due to overdosage or as a result of unusual sensitivity. The usual intravenous adult dose of naloxone is 0.4 mg or higher (please refer to naloxone product information for more information). The onset of naloxone effect may be delayed by 30 minutes or more. Concomitant efforts at respiratory resuscitation should be carried out. Since the duration of action of oxycodone may exceed that of the antagonist, the patient should be under continued surveillance and doses of the antagonist should be repeated as needed, or an antagonist infusion established, to maintain adequate respiration.
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 aberration 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 readily 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/OXYNORST.gif
