Boxed Warnings
Limitations of use. Because of the risks associated with the use of opioids, hydromorphone 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. Hydromorphone 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 hydromorphone. 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 receiving hydromorphone.
1 Name of Medicine
Hydromorphone hydrochloride.
2 Qualitative and Quantitative Composition
Hydromorphone hydrochloride, a hydrogenated ketone of morphine, is an opioid analgesic.
Hydromorphone hydrochloride is a fine, white or practically white, odourless, crystalline powder. It is freely soluble in water, sparingly soluble in ethanol and practically insoluble in ether.
Hydromorphone JUNO 2 mg/1 mL injection contains 2 mg hydromorphone hydrochloride in 1 mL solution.
Hydromorphone JUNO-HP 10 mg/1 mL injection contains 10 mg hydromorphone hydrochloride in 1 mL solution.
Hydromorphone JUNO-HP 50 mg/5 mL injection contains 50 mg hydromorphone hydrochloride in 5 mL solution.
Hydromorphone JUNO-XHP 50 mg/1 mL concentrated injection contains 50 mg hydromorphone hydrochloride in 1 mL solution.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
Hydromorphone JUNO injection solution, Hydromorphone JUNO-HP injection solution and Hydromorphone JUNO-XHP concentrated injection are presented as a clear, colourless to pale yellow solution in a clear glass ampoule.
4 Clinical Particulars
4.9 Overdose
Symptoms. Serious overdosage with hydromorphone is characterised by respiratory depression (reduced respiratory rate and/or tidal volume, cyanosis), extreme somnolence, progressing to stupor, coma or pneumonia aspiration, skeletal muscle flaccidity, cold and/or clammy skin, pupillary constriction, and possibly bradycardia, hypotension and death. Severe overdose may result in apnoea, pulmonary oedema, circulatory collapse and death.
Treatment. The primary concern in the treatment of opioid overdose is immediate supportive therapy with the establishment of adequate respiratory exchanges through the provision of, and maintenance of, adequate ventilation - patients may need ventilatory support up to and including endotracheal intubation and controlled ventilation. Adequate body temperature and fluid balance should be maintained. Oxygen, intravenous fluids, vasopressors and other supportive measures should be used as indicated.
Tolerance to the respiratory and CNS-depressant effects of opioids develops concomitantly with tolerance to the analgesic effects, therefore making respiratory depression unlikely in an opioid-tolerant patient taking the usual therapeutic doses of hydromorphone. Activated charcoal may reduce absorption of the drug if given within one to two hours after ingestion. A potentially serious recent oral ingestion of hydromorphone, if suspected, may be treated with activated charcoal in a patient who is fully conscious with an intact gag reflex or a secured airway. Initial dose of charcoal is 30 to 100 g in adults and 1 - 2 g/kg in children and is given as a slurry via nasogastric tube. 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 such as naloxone should be considered (please refer to naloxone product information for further information).
Caution should always be observed when using an opioid antagonist for the treatment of suspected hydromorphone overdose as the duration of action of hydromorphone may exceed that of the antagonist. Continuing surveillance is mandatory to prevent recurrence of respiratory depression and supportive care - including ventilatory and circulatory resuscitation/support when indicated - should always be provided. Additional doses of antagonist may be given as indicated by the clinical situation.
Opioid antagonists such as naloxone may precipitate an acute withdrawal in opioid-dependent patients and should be carefully titrated to the desired degree of reversal. The severity of an abstinence syndrome precipitated by administration of an opioid antagonist is contingent upon the degree of dependence and the dose of antagonist given. Too rapid or complete reversal may induce nausea, vomiting, sweating and circulatory stress and may reverse the desirable therapeutic effects (analgesia) as well.
Toxicity. 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.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
5 Pharmacological Properties
5.3 Preclinical Safety Data
Genotoxicity. Hydromorphone was non-genotoxic in the Ames test and the in vivo mouse micronucleus assay but positive in mouse lymphoma assay with metabolic activation. Similar findings have been reported with other opioid analgesics such as codeine and oxycodone.
Carcinogenicity. Long term carcinogenicity studies have not been performed.
6 Pharmaceutical Particulars
6.7 Physicochemical Properties
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSHYDHYD.gif CAS number. 71-68-1.
Molecular weight: 321.81.
Chemical name: 4,5α-epoxy-3-hydroxy-17-methylmorphinan-6-one hydrochloride.
7 Medicine Schedule (Poisons Standard)
Schedule 8.
Summary Table of Changes
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/HYJUHPST.gif
