Consumer medicine information

Hydromorphone Juno Hydromorphone Juno-HP Hydromorphone Juno-XHP

Hydromorphone hydrochloride

BRAND INFORMATION

Brand name

Hydromorphone JUNO/ JUNO-HP/ JUNO-XHP

Active ingredient

Hydromorphone hydrochloride

Schedule

SUMMARY CMI

HYDROMORPHONE JUNO/HYDROMORPHONE JUNO-HP/HYDROMORPHONE JUNO-XHP

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

1. Why am I using HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP?

HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP contain the active ingredient hydromorphone hydrochloride. Hydromorphone is used is used for the short-term relief of severe pain for which other treatment options have failed or otherwise unsuitable to provide sufficient management of pain.

For more information, see Section 1. Why am I using HYDROMORPHONE? in the full CMI.

2. What should I know before I use HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP?

Do not use if you have ever had an allergic reaction to hydromorphone or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use HYDROMORPHONE? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with hydromorphone and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP?

Your doctor will decide the appropriate dose for you.
A doctor or nurse will usually prepare and administer the injection or infusion.
Follow all instructions given to you by your doctor and pharmacist.

More instructions can be found in Section 4. How do I use HYDROMORPHONE? in the full CMI.

5. What should I know while using HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are receiving hydromorphone. Tell your doctor or pharmacist if you are taking/using any other medicines/substances that can make you feel drowsy.
Things you should not do	Do not stop using this medicine suddenly unless your doctor tells you to. Do not use more than your doctor tells you to.
Driving or using machines	Hydromorphone may cause drowsiness. If affected do not drive or operate machinery.
Drinking alcohol	Avoid alcohol. Alcohol may make you feel more sleepy and could increase the risk of serious side effects, such as shallow breathing with the risk of stopping breathing and loss of consciousness.
Looking after your medicine	Store below 25°C. Protect from light. Keep it where young children cannot reach it.

For more information, see Section 5. What should I know while using HYDROMORPHONE? in the full CMI.

6. Are there any side effects?

Hydromorphone injections may cause constipation, nausea, dizziness, drowsiness and be habit forming if used frequently over long periods.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

WARNING

Limitations of use: Hydromorphone should only be used when your doctor decides that other treatment options are not able to effectively manage your pain or you cannot tolerate them.

Hazardous and harmful use: Hydromorphone poses risks of abuse, misuse and addiction which can lead to overdose and death. Your doctor will assess any risks before prescribing this medicine and will monitor you regularly during treatment.

Life threatening respiratory depression: Hydromorphone can cause serious, life-threatening or fatal breathing problems (slow, shallow, unusual or no breathing), even when used as recommended. These problems can occur at any time during use, but the risk is greatest when starting treatment or following an increase in dose. The risk is higher in elderly, frail or debilitated patients, as well as those with kidney or liver impairment or existing lung/airway conditions. Your doctor will monitor you and change the dose as appropriate.

Use of other medicines: Using hydromorphone with other medicines/substances that make you drowsy, such as sleeping/anti-anxiety tablets (benzodiazepines), other pain relievers, antihistamines, antidepressants, antipsychotics, gabapentinoids (e.g. gabapentin and pregabalin), cannabis and alcohol may cause severe drowsiness, decreased awareness, breathing problems, coma and death. Your doctor will minimize the dose and duration of use and will monitor you for any signs and symptoms of breathing difficulties and sedation. You must not drink alcohol will being treated with hydromorphone.

FULL CMI

HYDROMORPHONE JUNO/HYDROMORPHONE JUNO-HP/HYDROMORPHONE JUNO-XHP

Active ingredient(s): Hydromorphone hydrochloride (hi-dro-morf-own hi-dro-klor-ide)

Consumer Medicine Information (CMI)

This leaflet provides important information about using hydromorphone. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using this medicine.

Where to find information in this leaflet:

1. Why am I using HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP?
2. What should I know before I use HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP?
3. What if I am taking other medicines?
4. How do I use HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP?
5. What should I know while using HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP?
6. Are there any side effects?
7. Product details

1. Why am I using HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP?

HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP contains the active ingredient hydromorphone hydrochloride.

Hydromorphone belongs to a group of medicines called opioid analgesics.

Hydromorphone is used to provide short term management of severe pain for which other treatment options have failed or are otherwise inappropriate to provide sufficient management of pain.

2. What should I know before I use HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP?

Warnings

Do not use HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP if:

You are allergic to hydromorphone, or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can use this medicine.
You suffer from shallow or difficult breathing or have any acute breathing problems such as acute asthma.
You have severe abdominal pain with bloating, cramps or vomiting.
You have a condition where your small bowel does not work properly.
You take medicine for depression called a 'monoamine oxidase inhibitor' or have taken any in the last two weeks.
You are pregnant or in labour.

Check with your doctor if you:

Take any medicines for any other condition.
Are severely drowsy, have a reduced level of consciousness or feel faint or dizzy upon standing.
Have heart problems or heart disease.
Have low blood pressure.
Have a chronic lung disease.
Suffer from sleep apnoea (temporarily stopping breathing while you sleep).
Have just drunk a large amount of alcohol, regularly drink large amounts of alcohol or have confusion and shaking due to stopping drinking alcohol.
Suffer from convulsions, fits or seizures.
Have a head injury, brain tumour or increased pressure in your head.
Are about to have surgery, had recent gastrointestinal surgery or have had other surgery in the last 24 hours.
Have chronic liver or kidney disease.
Have increased prostate size or difficulty passing urine.
Have problems with your gall bladder.
Have problems with or recent surgery of your bile duct.
Have inflammation of the pancreas.
Have adrenal glands which are not working properly.
Have an underactive thyroid gland.
Have a severe mental condition involving losing contact with reality or an inability to think clearly.
Suffer from major depression, anxiety or a personality disorder.
Have an addiction or history of abuse of alcohol, opioids or other drugs.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed. Low levels of opioids have been detected in human milk.

Hydromorphone given to the mother during labour can cause breathing problems and signs of withdrawal in the newborn.

Addiction

You can become addicted to hydromorphone even if you use it exactly as prescribed. Hydromorphone may become habit forming causing mental and physical dependence. If abused, it may become less able to reduce pain.

Dependence

As with all other opioid containing products, your body may become used to you receiving hydromorphone. Using it may result in physical dependence. Physical dependence means that you may experience withdrawal symptoms if you stop using hydromorphone suddenly, so it is important to use it exactly as directed by your doctor.

Tolerance

Tolerance to hydromorphone may develop, which means that the effect of the medicine may decrease. If this happens, more may be needed to maintain the same effect.

Withdrawal

Continue using your medicine for as long as your doctor tells you. If you stop having this medicine suddenly, your pain may worsen and you may experience some or all of the following withdrawal symptoms:

nervousness, restlessness, agitation, trouble sleeping or anxiety
body aches, weakness or stomach cramps
loss of appetite, nausea, vomiting or diarrhoea
increased heart rate, breathing rate or pupil size
watery eyes, runny nose, chills or yawning
increased sweating.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with hydromorphone and affect how it works.

Using hydromorphone with medicines that can make you feel drowsy may result in severe drowsiness, decreased awareness, breathing problems, coma and death. These medicines include:

sleeping tablets and other sedatives (including benzodiazepines and barbiturates)
gabapentinoids (e.g. gabapentin and pregabalin)
cannabis
antihistamines
anxiolytics (for managing anxiety)
general anaesthetics
antiemetics (for treating nausea and vomiting)
antidepressants (including tricyclic antidepressants),
antipsychotics (including phenothozines)
other opioids
alcohol.

Hydromorphone may enhance the action of neuromuscular blocking agents and affect your breathing.

Hydromorphone should not be used if you are taking non-selective monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping such treatment.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these could affect hydromorphone.

4. How do I use HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP?

How much to use

Your doctor will decide the appropriate dose for you.

When to use hydromorphone

You will be given hydromorphone injections as directed by your doctor.

If you begin to experience pain, tell your doctor as your dosage may have to be reviewed.

How to use hydromorphone

A doctor or nurse will usually prepare and administer the injection or infusion.

Hydromorphone injections can be given as a single injection or infusion into the vein. It can also be administered through a fine needle into the tissue under the skin or into the muscle.

Your doctor will decide the most appropriate way for you to be given hydromorphone. Using this medicine in a manner other than that prescribed by your doctor can be harmful to your health.

If you forget to use hydromorphone

If you miss your dose at the usual time, contact your doctor, nurse or pharmacist for advice.

You should not receive a double dose to make up for the dose that you missed, as this may increase the chance of getting unwanted side effects.

If you use too much hydromorphone

If you or someone else has received too much (overdose), and experience one or more of the symptoms below, call triple zero (000) for an ambulance. Keep the person awake by talking to them or gently shaking them every now and then. You should follow the above steps even if someone other than you have accidentally used hydromorphone that was prescribed for you.

If someone takes an overdose, they may experience one or more of the following symptoms:

slow, unusual or difficult breathing
drowsiness, dizziness or unconsciousness
slow or weak heartbeat
nausea or vomiting
convulsions or fits.

If you think you or someone else may have used too much hydromorphone you should immediately:

phone the Poisons Information Centre (by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

When seeking medical attention, take this leaflet and remaining medicine with you to show the doctor. Also tell them about any other medicines or alcohol which have been taken.

5. What should I know while using HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP?

Things you should do

Call your doctor straight away if you:

become pregnant
feel your pain is getting worse.

Remind any doctor, dentist or pharmacist you visit that you are using hydromorphone.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine.

Things you should not do

Do not stop using this medicine suddenly without your doctor's advice. If you stop taking this medicine suddenly, your pain may worsen and you may experience withdrawal symptoms.

Do not use hydromorphone to treat any other complaint unless your doctor tells you to.

Do not give this medicine to anyone else, even if they have the same condition as you.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how hydromorphone affects you.

Hydromorphone may cause drowsiness or impair mental and/or physical ability in some people.

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol may make you feel more sleepy, and could increase the risk of serious side effects, such as shallow breathing with the risk of stopping breathing and loss of consciousness.

Looking after your medicine

Store below 25°C.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

in the bathroom or near a sink
in the car or on windowsills.

Keep it where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Getting rid of any unwanted medicine

If your doctor tells you to stop having this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effects

What to do

Gastrointestinal and urinary related:

constipation
nausea or vomiting
difficulty urinating

Neurological and behavior related:

dizziness
drowsiness
headache

Skin related

sweating
itchiness or rash

Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effects

What to do

Breathing related

difficulty breathing or shallow breathing

Neurological and behaviour related:

light-headedness, fainting or dizziness especially when standing up
changes in mood
drowsiness or feeling extremely sedated
feeling disorientated or having hallucinations
seizures (fits)

Heart related:

slow, fast or irregular heartbeats

Gastrointestinal and urinary related:

severe stomach pain with nausea or vomiting
difficulty urinating

Allergy related

shortness of breath, swelling of the face, lips, tongue or other parts of the body

Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP contains

Active ingredient (main ingredient)	hydromorphone hydrochloride
Other ingredients (inactive ingredients)	sodium citrate citric acid monohydrate sodium chloride water for injections.
Allergen information	This medicine does not contain lactose, sucrose, gluten, tartrazine or other azo dyes.

Do not take this medicine if you are allergic to any of the ingredients contained in this product.

What HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP looks like

A clear, colourless to pale yellow solution in a clear glass ampoule.

Australian registration numbers:

HYDROMORPHONE JUNO 2 mg in 1 mL injection solution AUST R 303503.
HYDROMORPHONE JUNO-HP 10 mg in 1 mL injection solution AUST R 303502.
HYDROMORPHONE JUNO-HP 50 mg in 5 mL injection solution AUST R 303504.
HYDROMORPHONE JUNO-XHP 50 mg in 1 mL concentrated injection AUST R 303505.

Who distributes HYDROMORPHONE JUNO/JUNO-HP/JUNO-XHP

Juno Pharmaceuticals Pty Ltd
15-17 Chapel Street
Cremorne VIC 3121

This leaflet was prepared in January 2024.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

Hydromorphone JUNO/ JUNO-HP/ JUNO-XHP

Active ingredient

Hydromorphone hydrochloride

Schedule

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

4.1 Therapeutic Indications

For the short-term management of severe pain for which other treatment options have failed, are contraindicated, not tolerated, or are otherwise inappropriate to provide sufficient management of pain.

4.2 Dose and Method of Administration

Warning.

Hydromorphone JUNO-HP injection (high potency) and Hydromorphone JUNO-XHP concentrated injection (extra high potency) are highly concentrated solutions of hydromorphone intended for use in opioid-tolerant patients. Do not confuse Hydromorphone JUNO-HP injection or Hydromorphone JUNO-XHP with standard parenteral formulations of Hydromorphone JUNO or other opioids. Overdose and death could result.
Product is for single use in one patient only. Discard any residue.

General.

Hydromorphone, like other opioids, may cause clinically significant physical dependence usually after several weeks of continued opioid therapy, but in some patients it may be clinically relevant after a shorter treatment period (see Section 4.4 Special Warnings and Precautions for Use, Tolerance, dependence and withdrawal). Tolerance, i.e. when increasingly larger doses are required to produce a given clinical effect, is initially manifested as a shortened duration of action followed by a decrease in the intensity of analgesic effect. Tolerance is a normal and expected sequela of continued opioid therapy and may become a significant consideration. Hydromorphone JUNO dosage, in these patients, should be titrated to the desired analgesic effect.

Adult.

Individualisation of dosage. As with other opioid analgesics, safe and effective administration of Hydromorphone JUNO preparations to patients with pain depends upon a comprehensive assessment of the patient. The nature of the pain (severity, frequency, aetiology and pathophysiology) as well as the concurrent medical status of the patient will affect selection of the starting dosage.
Owing to the varied response observed to opioids between individuals, it is recommended that all patients be started at a conservative dose of hydromorphone and titrated to an adequate level of analgesia, balanced with an acceptable level of adverse effect(s).
Non opioid-tolerant patients. The recommended initial dose is as follows:

Intramuscular or subcutaneous.

1 to 2 mg every four to six hours.

Intravenous.

0.5 to 1.0 mg (given slowly over 2 to 3 minutes).
Intravenous or subcutaneous administration is usually not painful.

Patient-controlled analgesia (PCA).

There are limited data available on the use of intravenous hydromorphone administered as PCA. One regimen described in the literature is as follows: Adequate analgesia should be established prior to commencement of the PCA. A background continuous intravenous infusion of 0.1 mg per hour should be used together with patient-administered bolus doses of 0.2 mg at no more than 5 minutely intervals and up to a maximum of 1.2 mg per hour.

Continuous intravenous infusion.

Limited data are available. An infusion of up to 0.3 mg per hour has been used in a small number of patients.
In general, and irrespective of route of administration, elderly patients may require lower doses of Hydromorphone JUNO preparations (see Section 4.4 Special Warnings and Precautions for Use, Use in the elderly).
Patients currently receiving opioids. When converting patients currently receiving opioids to a Hydromorphone JUNO preparation, both the dose of hydromorphone and the duration of its analgesic effect will vary substantially depending on the patient's opioid tolerance. A hydromorphone dose should be selected and adjusted so that at least 3-4 hours of pain relief is achieved. In patients taking opioid analgesics, the starting dose of hydromorphone should be based on the prior daily opioid dose. This should be done by converting the total daily dose of the previous opioid to an equivalent total daily dose of hydromorphone using the Equianalgesic table. For opioids not in the table, first estimate the equivalent total daily dose of morphine, then use the table to determine the equivalent total daily dose of hydromorphone (see Table 1).

Once the total daily dosage of hydromorphone has been estimated, it should be divided into the desired number of doses. Since there is individual variation in response to different opioid drugs, only 1/2 to 2/3 of the estimated dose of hydromorphone calculated from the Equianalgesic table should be given for the first few doses, then increased as needed according to the patient's response to its analgesic effect.
The Hydromorphone JUNO range of products (see Section 2 Qualitative and Quantitative Composition) provides total flexibility in respect of dose and route of administration. Hence, the appropriate Hydromorphone JUNO dosage form should be carefully considered, consistent with the route of administration, to achieve the pain relief sought for the patient.
Periodic reassessment after initial dosing is always required. If pain management is not satisfactory and, in the absence of significant opioid-induced adverse events, the hydromorphone dose may be increased gradually. If excessive opioid side effects are observed early during the dosing interval, the hydromorphone dose should be reduced. If this results in breakthrough pain at the end of the dosing interval, the dosing interval may need to be shortened. Dose titration should be guided by the need for analgesia rather than the absolute dose of opioid employed.
Hydromorphone JUNO-HP injection (HP = high potency) and Hydromorphone JUNO-XHP concentrated injection (XHP = extra high potency) are only recommended for patients who are already receiving high doses of parenteral opioids where the volume required for parenteral administration (to achieve the high dose) becomes unacceptably large for the chosen route of administration (e.g. subcutaneous).
Hydromorphone JUNO-XHP 50 mg/1 mL concentrated injection must be diluted with an appropriate sterile diluent (e.g. 0.9% sodium chloride solution (saline), 5% glucose solution, water for injection solution) to a suitable concentration that can be tolerated by the patient.
Continuous subcutaneous infusion has also been used as a method of delivering large daily doses of hydromorphone in opioid-tolerant patients with severe pain.
Transferring patients between oral and parenteral hydromorphone. Switching patients from parenteral hydromorphone to oral hydromorphone (available from other sponsors) should be guided by the sensitivity of the individual patient. The oral starting dose should not be overestimated (for oral bioavailability, see Section 5.2 Pharmacokinetic Properties, Metabolism).

Children.

Safety and efficacy have not been established in children.

4.3 Contraindications

Hydromorphone JUNO preparations are contraindicated in patients with: known hypersensitivity to hydromorphone or to any of the ingredients; severe respiratory disease, acute respiratory disease, respiratory depression, status asthmaticus, paralytic ileus, concurrent monoamine oxidase inhibitors (MAOIs) or within 14 days of such therapy, pregnancy; premature infants and children, or during labour for delivery of premature infants.

4.4 Special Warnings and Precautions for Use

Tolerance and opioid use disorder (abuse and dependence).

Tolerance, physical and psychological dependence, and opioid use disorder (OUD) may develop upon repeated administration of opioids.

Hazardous and harmful use.

Hydromorphone JUNO preparations contain the opioid hydromorphone, a potential drug of abuse, misuse and addiction. Addiction can occur in patients appropriately prescribed hydromorphone at recommended doses.
Abuse or intentional misuse of hydromorphone may result in overdose and/or death. The risk of developing OUD is increased in patients with a personal or family history (parents or siblings) of substance abuse disorders (including alcohol and prescription and illicit drugs) in current tobacco users or in patients with a personal history of other mental health disorders (e.g. major depression, anxiety and personality disorders). The risk also increases the longer the drug is used and with higher doses. Patients should be assessed for their risks for opioid abuse or addiction prior to being prescribed hydromorphone.
All patients receiving opioids should be routinely monitored for signs of drug-seeking behaviour (e.g. too early requests for refills), misuse and abuse. Opioids are sought by people with addiction and may be subject to diversion. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the safe storage and proper disposal of any unused drug (see Section 6.4 Special Precautions for Storage; Section 6.6 Special Precautions for Disposal). Caution patients that abuse or intentional misuse of oral or transdermal forms of opioids by parenteral administration can result in serious adverse events, such as overdose and/or death. For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered.
Patients should be advised not to share hydromorphone with anyone else.

Tolerance, dependence and withdrawal.

Neuroadaptation of the opioid receptors to repeated administration of opioids can produce tolerance and physical dependence. Tolerance is the need for increasing doses to maintain analgesia. Tolerance may occur to both the desired and undesired effects of the opioid.
Physical dependence, which can occur after several days to weeks of continued opioid usage, results in withdrawal symptoms if the opioid is ceased abruptly or the dose is significantly reduced. Withdrawal symptoms can also occur following the administration of an opioid antagonist (e.g. naloxone) or partial agonist (e.g. buprenorphine). Withdrawal can result in some or all of the following symptoms: dysphoria, restlessness/agitation, lacrimation, rhinorrhoea, yawning, sweating, chills, myalgia, mydriasis, irritability, anxiety, increasing pain, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhoea, increased blood pressure, increased respiratory rate and increased heart rate.
Opioid withdrawal has been well described in the literature and its severity in a particular patient can vary from mild discomfort to potential cardiovascular collapse. Without treatment most observable symptoms resolve in 5-14 days. A period of "subacute withdrawal" lasting up to 6 months has also been described in which previously dependent patients experience difficulty concentrating, insomnia, irritability, myalgias and autonomic instability.
Various regimens have been described for treatment of withdrawal, including but not limited to methadone substitution, clonidine, benzodiazepines, and phenothiazines. Supportive care is essential and associated symptoms, such as dehydration and gastrointestinal disturbances, should be treated accordingly.
When discontinuing hydromorphone in a person who may be physically-dependent, the drug should not be ceased abruptly but withdrawn by tapering the dose gradually (see Ceasing opioids; see Section 4.2 Dose and Method of Administration).

Respiratory depression.

Serious, life-threatening or fatal respiratory depression can occur with the use of opioids even when used as recommended. It can occur at any time during the use of hydromorphone, but the risk is greatest during initiation of therapy or following an increase in dose. Patients should be monitored closely for respiratory depression at these times.
The risk of life-threatening respiratory depression is also higher in elderly, frail, or debilitated patients and in patients with existing renal or hepatic impairment, or impairment of respiratory function (e.g. chronic obstructive pulmonary disease; asthma). Opioids should be used with caution and with close monitoring in these patients (see Section 4.2 Dose and Method of Administration). The use of opioids is contraindicated in patients with severe respiratory disease, acute respiratory disease and respiratory depression (see Section 4.3 Contraindications).
Respiratory depression occurs most frequently in overdose situations, and in those suffering from conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic doses may dangerously decrease pulmonary ventilation.
Hydromorphone should be used with extreme caution in patients with cor pulmonale, patients having a substantially decreased respiratory reserve (e.g. kyphoscoliosis), hypoxia or hypercapnia. In such patients even usual therapeutic doses of opioid analgesics may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnoea.
The risk of respiratory depression is greater with the use of high doses of opioids, especially high potency and modified release formulations, and in opioid naïve patients. Initiation of opioid treatment should be at the lower end of the dosage recommendations with careful titration of doses to achieve effective pain relief. Careful calculation of equianalgesic doses is required when changing opioids or switching from immediate release to modified release formulations, (see Section 4.2 Dose and Method of Administration), together with consideration of pharmacological differences between opioids. Consider starting the new opioid at a reduced dose to account for individual variation in response.

Sleep-related breathing disorders.

Opioids may cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent manner in some patients. Opioids may also cause worsening of pre-existing sleep apnoea (see Section 4.8 Adverse Effects (Undesirable Effects)). In patients who present with CSA consider decreasing the total opioid dosage.

Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol.

Concomitant use of opioids and benzodiazepines or other CNS depressants, including alcohol, may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of hydromorphone with CNS depressant medicines, such as other opioid analgesics, benzodiazepines, gabapentinoids, cannabis, sedatives, hypnotics, tricyclic antidepressants, antipsychotics, antihistamines, centrally-active antiemetics and other CNS depressants, should be reserved for patients for whom other treatment options are not possible. If a decision is made to prescribe hydromorphone concomitantly with any of the medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible. Patients should be followed closely for signs and symptoms of respiratory depression and sedation. Patients and their caregivers should be made aware of these symptoms. Patients and their caregivers should also be informed of the potential harms of consuming alcohol while receiving hydromorphone.

Use of opioids in chronic (long-term) non-cancer pain (CNCP).

Opioid analgesics have an established role in the treatment of acute pain, cancer pain and palliative and end-of-life care. Current evidence does not generally support opioid analgesics in improving pain and function for most patients with chronic non-cancer pain. The development of tolerance and physical dependence and risks of adverse effects, including hazardous and harmful use, increase with the length of time a patient takes an opioid. The use of opioids for long-term treatment of CNCP is not recommended.
The use of an opioid to treat CNCP should only be considered after maximised non-pharmacological and non-opioid treatments have been tried and found ineffective, not tolerated or otherwise inadequate to provide sufficient management of pain. Opioids should only be prescribed as a component of comprehensive multidisciplinary and multimodal pain management.
Opioid therapy for CNCP should be initiated as a trial in accordance with clinical guidelines and after a comprehensive biopsychosocial assessment has established a cause for the pain and the appropriateness of opioid therapy for the patient (see Hazardous and harmful use, above). The expected outcome of therapy (pain reduction rather than complete abolition of pain, improved function and quality of life) should be discussed with the patient before commencing opioid treatment, with agreement to discontinue treatment if these objectives are not met.
Owing to the varied response to opioids between individuals, it is recommended that all patients be started at the lowest appropriate dose and titrated to achieve an adequate level of analgesia and functional improvement with minimum adverse reactions. Immediate-release products should not be used to treat chronic pain, but may be used for a short period in opioid-naïve patients to develop a level of tolerance before switching to a modified-release formulation. Careful and regular assessment and monitoring is required to establish the clinical need for ongoing treatment. Discontinue opioid therapy if there is no improvement of pain and/or function during the trial period or if there is any evidence of misuse or abuse.
Treatment should only continue if the trial has demonstrated that the pain is opioid responsive and there has been functional improvement. The patient's condition should be reviewed regularly and the dose tapered off slowly if opioid treatment is no longer appropriate (see Ceasing opioids).

Accidental ingestion/exposure.

Accidental ingestion or exposure of hydromorphone, especially by children, can result in a fatal overdose. Patients and their caregivers should be given information on safe storage and disposal of unused hydromorphone (see Section 6.4 Special Precautions for Storage; Section 6.6 Special Precautions for Disposal).

Hyperalgesia.

Hyperalgesia may occur with the use of opioids, particularly at high doses. Hyperalgesia may manifest as an unexplained increase in pain, increased levels of pain with increasing opioid dosages or diffuse sensitivity not associated with the original pain. Hyperalgesia should not be confused with tolerance (see Tolerance, dependence and withdrawal). If opioid induced hyperalgesia is suspected, the dose should be reduced and tapered off if possible. A change to a different opioid may be required.

Ceasing opioids.

Abrupt discontinuation or rapid decreasing of the dose in a person physically dependent on an opioid may result in serious withdrawal symptoms and uncontrolled pain (see Tolerance, dependence and withdrawal). Such symptoms may lead the patient to seek other sources of licit or illicit opioids. Opioids should not be ceased abruptly in a patient who is physically dependent but withdrawn by tapering the dose slowly. Factors to take into account when deciding how to discontinue or decrease therapy include the dose and duration of the opioid the patient has been taking, the type of pain being treated and the physical and psychological attributes of the patient. A multimodal approach to pain management should be in place before initiating an opioid analgesic taper. During tapering, patients require regular review and support to manage any increase in pain, psychological distress and withdrawal symptoms.
There are no standard tapering schedules suitable for all patients and an individualised plan is necessary. In general, tapering should involve a dose reduction of no more than 10 percent to 25 percent every 2 to 4 weeks (see Section 4.2 Dose and Method of Administration). If the patient is experiencing increased pain or serious withdrawal symptoms, it may be necessary to go back to the previous dose until stable before proceeding with a more gradual taper.
When ceasing opioids in a patient who has a suspected opioid use disorder, the need for medication assisted treatment and/or referral to a specialist should be considered.

Endocrine effects.

Opioids may influence the hypothalamic-pituitary-adrenal or -gonadal axes. Some changes that can be seen include an increase in serum prolactin, and decreases in plasma cortisol and testosterone. Clinical symptoms may manifest from these hormonal changes.

Special risk patients.

In general, opioids should be given with caution and the initial dose should be reduced in the debilitated and those with severe impairment of pulmonary function; sleep apnoea, myxoedema or hypothyroidism; adrenocortical insufficiency (e.g. Addison's Disease); CNS depression or coma; toxic psychosis; prostatic hypertrophy or urethral stricture; gall bladder disease; acute alcoholism; delirium tremens; pancreatitis, constipation or following gastrointestinal surgery as opioids are known to impair intestinal motility and should not be used until the physician is assured of normal bowel function. Should paralytic ileus be suspected or occur during use, hydromorphone preparations should be discontinued immediately. The administration of opioid analgesics including hydromorphone may obscure the diagnoses or clinical course in patients with acute abdominal conditions and may aggravate pre-existing convulsions in patients with convulsive disorders. Reports of mild to severe seizures and myoclonus have been reported in severely compromised patients, administered high doses of parenteral hydromorphone, for cancer and severe pain.

Head injury and increased intracranial pressure.

The respiratory depressant effects of hydromorphone with carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or pre-existing increase in intracranial pressure. Opioid analgesics, including hydromorphone, may produce effects which can obscure the clinical course and neurologic signs of further increase in intracranial pressure in patients with head injuries.

Hypotensive effect.

Opioid analgesics, including hydromorphone, may cause severe hypotension in an individual whose ability to maintain blood pressure has already been compromised by depleted blood volume or a concurrent administration of drugs such as phenothiazines or general anaesthetics (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Therefore, hydromorphone should be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure. Hydromorphone may produce orthostatic hypotension in ambulatory patients.

Use in surgery.

Hydromorphone injections should be used with caution pre- or intra-operatively and within the first 24 hours post-operatively.
Opioid analgesics including hydromorphone should also be used with caution in patients requiring biliary tract procedures since it may cause spasm of the sphincter of Oddi.

Use in hepatic impairment.

Opioids should be given with caution and the initial dose should be reduced in those with hepatic impairment.

Use in renal impairment.

Opioids should be given with caution and the initial dose should be reduced in those with renal impairment.

Use in the elderly.

Elderly subjects have been shown to have at least twice the sensitivity (as measured by EEG changes) of young adults to some opioids. When administering hydromorphone preparations to the elderly, the initial dose should be reduced (see Section 4.2 Dose and Method of Administration).

Paediatric use.

Safety and efficacy have not been established in children.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Central nervous system (CNS).

The concomitant use of other central nervous system depressants which include, but are not limited to sedatives (including benzodiazepines), cannabis, antihistamines, anxiolytics, hypnotics, general anaesthetics (e.g. barbiturates), phenothiazines, tranquillisers, antiemetics, antidepressants (including tricyclic antidepressants), antipsychotics, neuroleptics, other opioids or alcohol may produce additive depressant effects. Respiratory depression, hypotension and profound sedation, coma or death may occur (see Section 4.4 Special Warnings and Precautions for Use, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol). The dose and duration of concomitant use should be limited (see Section 4.4 Special Warnings and Precautions for Use).
The concomitant use of opioids and gabapentinoids (gabapentin and pregabalin) increases the risk of opioid overdose, respiratory depression and death.
Hydromorphone should not be given to patients taking non-selective MAOIs or within 14 days of stopping such treatment.
Opioid analgesics including hydromorphone may enhance the action of neuromuscular blocking agents and produce an extensive degree of respiratory depression.
See Section 6.2 Incompatibilities for further information on pharmaceutical incompatibility.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No effects have been observed on male or female fertility or sperm parameters in rats.
(Category C)
Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing harmful effects on the human foetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.
Literature reports of hydromorphone hydrochloride administered to pregnant golden hamsters showed that hydromorphone is teratogenic at subcutaneous (SC) doses greater than 14 mg/kg. Evidence of a teratogenic effect has also been reported in the literature in mice and hamsters but was not observed in rat and rabbit studies conducted by the sponsor. The relevance of these findings to humans is unknown since there are no well-controlled studies of hydromorphone in pregnant women.
A pre- and post-natal study in rats showed that there was an increase in pup mortality and reduced body weight gain in the early post-natal period, associated with maternal toxicity. No effects on continued pup development or reproductive performance were observed.
Like other opioid analgesics, hydromorphone may cause respiratory depression in the newborn infant. Hydromorphone should only be used during labour after considering the needs of the mother against the risk to the foetus. In long-term treatment during pregnancy, the risk of neonatal withdrawal should be considered.
Low levels of opioid analgesics have been detected in human milk. As a general rule, breast feeding should not be undertaken while a patient is receiving hydromorphone since it, and other drugs in this class, may be excreted in the milk.

4.7 Effects on Ability to Drive and Use Machines

Hydromorphone may cause drowsiness and may increase the effects of alcohol. If affected, do not drive a motor vehicle or operate machinery.

4.8 Adverse Effects (Undesirable Effects)

The adverse effects of hydromorphone are similar to those of other opioid agonist analgesics, and represent established pharmacological effects of the drug class. The major hazards include respiratory depression and apnoea. To a lesser degree, circulatory depression, respiratory arrest, shock and cardiac arrest have occurred.
Adverse effects reported commonly (frequency > 1%) seem to be more prominent in ambulatory patients and in those not experiencing severe pain. Syncopal reactions and related symptoms in ambulatory patients may be alleviated if the patient lies down.

Cardiovascular disorders.

Common: hypotension.
Uncommon: bradycardia, hypertension, palpitation, tachycardia.
Unknown: flushing.

Eye disorders.

Uncommon: blurred vision, diplopia, miosis, visual impairment.

Gastrointestinal disorders.

Very common: constipation, nausea.
Common: abdominal pain, dry mouth, vomiting.
Uncommon: cramps, diarrhoea, dysgeusia (taste alteration), paralytic ileus.

General disorders and administration site conditions.

Common: asthenia, injection site reactions (following parenteral administration only).
Uncommon: chills, drug tolerance, drug withdrawal syndrome, drug withdrawal syndrome neonatal, peripheral oedema, fatigue, malaise.

Hepatobiliary disorders.

Uncommon: biliary colic, increased hepatic enzymes.

Immune system disorders.

Uncommon: anaphylactic reactions, hypersensitivity reactions (including oropharyngeal swelling).

Metabolism and nutrition disorders.

Common: anorexia.

Nervous system disorders.

Very common: dizziness, somnolence.
Common: headache, light-headedness, sedation.
Uncommon: convulsions, dyskinesia, faintness, hyperalgesia, increased intracranial pressure, myoclonus, uncoordinated muscle movement, muscle rigidity, paraesthesia, syncope, tremor, weakness.
Rare: lethargy.
Not known: central sleep apnoea syndrome.

Psychiatric disorders.

Common: anxiety, confusional state, dysphoria, euphoria, insomnia, nervousness.
Uncommon: agitation, drug dependence, alterations of mood (apprehension, depression, floating feelings), transient hallucinations, disorientation, nightmares.

Renal and urinary disorders.

Common: urinary retention.
Uncommon: antidiuretic effects, urinary hesitancy.

Reproductive system and breast disorders.

Uncommon: erectile dysfunction.

Respiratory, thoracic and mediastinal disorders.

Uncommon: bronchospasm, dyspnoea, laryngospasm, respiratory depression.

Skin and subcutaneous tissue disorders.

Common: hyperhidrosis (sweating), pruritus, rash.
Uncommon: urticaria and other skin rashes.
Key: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).

Other.

In clinical trials, neither local tissue irritation nor induration was observed at the site of subcutaneous injection of hydromorphone-HP injection; pain at the injection site was rarely observed.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

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.
Toxic leukoencephalopathy has been observed with hydromorphone overdose.

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

5.1 Pharmacodynamic Properties

Mechanism of action.

Hydromorphone is an opioid agonist with no antagonist activity. Many of the effects described below for hydromorphone are common to the class of mu-opioid agonist analgesics (e.g. morphine). In some instances, data may not exist to distinguish the effects of hydromorphone from those observed with other opioid analgesics. However, in the absence of data to the contrary, it is assumed that hydromorphone would mirror the pharmacological effects of mu-agonist opioids.
Although estimates vary, hydromorphone is thought to be approximately eight times as potent (by weight) as morphine. It is estimated that 1.3 mg of intramuscular (IM) hydromorphone is equianalgesic to 10 mg of IM morphine. The relative potency, (based on a single dose bioassay) of oral hydromorphone was found to be approximately one-fifth that of IM hydromorphone - this ratio being similar to that for morphine. However, clinical experience with morphine indicates that this 1:5 ratio changes to 1:2 with chronic oral dosing. Such a change in oral-parenteral relative potency may also occur with hydromorphone.
Opioid analgesics exert their primary effects on the central nervous system (CNS) and organs containing smooth muscle. The principal actions of therapeutic value are analgesia and sedation. A significant feature of the analgesia is that it can occur without loss of consciousness. Opioid analgesics also suppress the cough reflex and may cause respiratory depression, mood changes, mental clouding, euphoria, dysphoria, nausea, vomiting and electroencephalographic changes. The precise mode of analgesic action of opioid analgesics is unknown. However, specific CNS opiate receptors have been identified. Opioids are believed to express their pharmacological effects through interaction with these receptors.
Opioids depress the respiratory reflex by a direct effect on brain stem respiratory centres and reducing the responsiveness of these centres to increases in carbon dioxide.
Opioids can cause a marked increase in biliary tract pressure as a result of spasm of the sphincter of Oddi. Gastric, biliary and pancreatic secretions are decreased by opioids. Opioids cause a reduction in gastrointestinal motility. Digestion of food in the small intestine is delayed and propulsive contractions are decreased resulting in constipation.
Certain opioids produce peripheral vasodilation which may result in orthostatic hypotension. Release of histamine may occur with opioids and may contribute to drug-induced hypotension. Other manifestations of histamine release may include pruritus, flushing and red eyes.
Effects on the myocardium after intravenous (IV) administration of opioids are not significant in normal persons, vary with different opioid analgesic agents and vary with the haemodynamic state of the patient, state of hydration and sympathetic drive.
In vitro and animal studies indicate various effects of natural opioids, such as morphine, on components of the immune system; the clinical significance of these findings is unknown. Whether hydromorphone, a semisynthetic opioid, has immunological effects similar to morphine is unknown.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Adult.

Absorption.

When administered in tablet form (in dosage forms available from other sponsors), hydromorphone (8 mg) is rapidly absorbed after oral administration and the plasma half-life ranges from 2.3-2.6 hours.

Distribution.

Following intravenous administration of hydromorphone to normal volunteers, the mean half-life of elimination was 2.64 ± 0.88 hours. The mean volume of distribution was 301 L, suggesting extensive tissue uptake. Hydromorphone is rapidly removed from the blood stream and distributed to skeletal muscle, kidneys, liver, intestinal tract, lungs, spleen and brain. Hydromorphone also crosses the placental membranes. Total plasma clearance following IV administration is approximately 1.85 L/min.

Metabolism.

Hydromorphone undergoes extensive first-pass metabolism resulting in oral bioavailability of about 25%.
Hydromorphone metabolism is typical of that seen for the 5-ring morphinan derivatives - the primary pathway being glucuronidation in the liver.

Excretion.

The major metabolite, hydromorphone-3-glucuronide (H3G), small amounts of parent drug and the minor 6-hydroxy reduction metabolites are excreted primarily in the urine.
The 3-glucuronide metabolite of hydromorphone (H3G) can be isolated in a ratio of roughly 25:1 to parent drug after oral administration of hydromorphone to patients with normal renal function. In patients with renal impairment, suspected of having adverse reactions due to the accumulation of metabolite, H3G levels were identified at levels more than four times higher than predicted. Such accumulation of H3G may be responsible for the psychomimetic reactions occasionally reported in patients taking high doses of hydromorphone. Accumulation of neuroexcitatory metabolites is also postulated as the aetiology of similar and occasionally severe dystonic reactions reported with high doses of morphine and semi-synthetic opioids.

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

6.1 List of Excipients

Sodium citrate dihydrate; citric acid monohydrate; sodium chloride; water for injections.

6.2 Incompatibilities

Hydromorphone hydrochloride injection is physically compatible and chemically stable for at least 24 hours at 25°C protected from light in most common large volume parenteral solutions which do not have a pH > 7.
Hydromorphone hydrochloride injection is incompatible with soluble barbiturates.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

Container type.

Hydromorphone JUNO 2 mg/1 mL injection is presented in clear glass ampoules.
Hydromorphone JUNO-HP 10 mg/1 mL injection is presented in clear glass ampoules.
Hydromorphone JUNO-HP 50 mg/5 mL injection is presented in clear glass ampoules.
Hydromorphone JUNO-XHP 50 mg/1 mL concentrated injection is presented in clear glass ampoules.

Pack sizes.

5 ampoules per pack.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

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.

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