Consumer medicine information

Oxycodone Juno solution for injection or infusion

Oxycodone hydrochloride

BRAND INFORMATION

Brand name

Oxycodone Juno Solution for injection or infusion

Active ingredient

Oxycodone hydrochloride

Schedule

S8

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Oxycodone Juno solution for injection or infusion.

What is in this leaflet

This leaflet answers some common questions about Oxycodone Juno solution for injection or infusion ("injection or infusion").

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given this medicine against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, talk to your doctor or pharmacist.

Keep this leaflet in a safe place.

You may need to read it again.

What Oxycodone Juno injection or infusion is given for

Oxycodone Juno solution for injection or infusion contains oxycodone hydrochloride.

Oxycodone belongs to a group of medicines called opioid analgesics.

Oxycodone Juno injection or infusion is given to relieve moderate to severe pain. It can be given as a single injection or as an infusion into a vein or into the tissue under the skin.

Your doctor, however, may prescribe it for another purpose.

Ask your doctor if you have any questions about why it has been prescribed for you.

As with all strong painkillers, your body may become used to you having oxycodone. Being given it may result in physical dependence. Physical dependence means that you may experience withdrawal symptoms if you stop having oxycodone suddenly, so it is important that you are given Oxycodone Juno injection or infusion exactly as directed by your doctor. This medicine is only available with a doctor's prescription.

Before you are given Oxycodone Juno injection or infusion

Long-term use of Oxycodone Juno injection or infusion may result in a decrease in sex hormone levels which may affect sperm production in men and the menstrual cycle in females. Talk to your doctor if you have any concerns.

When you must not have it

You should not be given Oxycodone Juno injection or infusion if you:

  • have any breathing problems such as acute asthma, respiratory depression (breathing slows or weakens) or other obstructive airways disease
  • are severely drowsy or have a reduced level of consciousness.
  • suffer from irregular or fast heartbeats or changes in the way the heart beats
  • have heart disease due to longterm lung disease
  • have just consumed a large amount of alcohol, regularly consume large amounts of alcohol or have confusion and shaking due to alcohol withdrawal
  • suffer anxiety from taking hypnotics, medicines that are given to help people sleep
  • suffer from convulsions, fits or seizures
  • have a head injury, brain tumour, or have raised pressure within the head, brain or spinal cord
  • have sudden, severe abdominal pain or chronic constipation
  • have a condition where your stomach empties more slowly than it should, or your small bowel does not work properly
  • have severe kidney disease
  • have moderate to severe liver disease
  • are about to have surgery on your spine for pain relief in the next 6 hours
  • take a medicine for depression called a 'monoamine oxidase inhibitor' or have taken any in the last two weeks.

You should not have Oxycodone Juno injection or infusion if you are allergic to oxycodone, opioid painkillers, or any of the ingredients listed at the end of this leaflet.

You should not continue to have Oxycodone Juno infusion 50 mg in 1 mL if you have been given Oxycodone Juno infusion 50 mg in 1 mL for more than 4 consecutive weeks.

Do not use this medicine after the expiry date (EXP) printed on the pack.

If you are given it after the expiry date has passed, it may not work very well.

Do not use this medicine if the packaging is torn or shows signs of tampering or if the injection shows any visible signs of deterioration.

You should not be given this medicine if you are pregnant or intend to become pregnant whilst being given this medicine.

Like most medicines of this kind, Oxycodone Juno injection or infusion is not recommended to be given during pregnancy. Your doctor will discuss the risks of having it if you are pregnant.

You should not be given this medicine if you are 18 years of age or younger.

Safety and effectiveness in children younger than 18 years of age have not been established.

Before you start to have it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes. Tell your doctor if you have or have had any medical conditions, especially the following:

  • low blood pressure
  • increased prostate size or difficulty passing urine
  • chronic lung, liver or kidney disease
  • disease of your gall bladder or bile duct
  • inflammation of the pancreas
  • underactive adrenal glands
  • underactive thyroid gland
  • inflammatory bowel disease
  • you have had recent abdominal surgery, you are about to have surgery or you have had surgery within the last 24 hours
  • severe mental condition involving losing contact with reality, hearing voices or an inability to think clearly
  • an addiction or history of abuse of alcohol, opioids or other drugs.

This medicine is not recommended to be used during labour.

Oxycodone given to the mother during labour can cause breathing problems and signs of withdrawal in the newborn Oxycodone can pass into the breast milk and can affect the baby. Your doctor can discuss the risks involved.

If you have not told your doctor about any of the above, tell them before you have Oxycodone Juno injection or infusion.

Taking other medicines

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

Some medicines, dietary supplementsand Oxycodone Juno injection or infusion may interfere with each other. These include:

  • medicines to treat depression, psychiatric or mental disorders.
  • medicines to treat depression belonging to a group called monoamine oxidase inhibitors must be stopped 14 days before Oxycodone Juno injection or infusion is given
  • medicines to help you sleep
  • medicines to put you to sleep during an operation or procedure
  • medicines to relax your muscles
  • medicines to lower blood pressure
  • quinidine and other medicines to treat the heart
  • medicines to treat convulsions e.g. phenytoin, carbamazepine
  • medicines to thin the blood e.g. coumarin derivatives such as warfarin
  • cimetidine, a medicine to treat stomach ulcers or heartburn
  • medicines to relieve stomach cramps or spasms, to prevent travel sickness,
  • medicines to treat Parkinson's disease
  • medicines to treat urinary incontinence
  • medicines to stop nausea or vomiting e.g. metoclopramide
  • other pain relievers including other opioids
  • antibiotics, e.g. clarithromycin erythromycin, rifampicin
  • medicines to treat fungal infections e.g. ketoconazole
  • alcohol
  • medicine to treat HIV infection and AIDS e.g. ritonavir
  • St John's wort (a herbal preparation)
  • grapefruit and grapefruit juice

These medicines, dietary supplements or alcohol may be affected by Oxycodone Juno injection or infusion, may affect how well Oxycodone Juno injection or infusion works or may increase side effects. You may need to use different amounts of the medicines, or take different medicines.

Your doctor or pharmacist has more information on medicines to be careful with or avoid while using this medicine.

How Oxycodone Juno injection or infusion is given

How much is given

Your doctor will decide the appropriate dose for you.

How it is given

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

Oxycodone Juno injection or infusion 10 mg in 1 mL or 20 mg in 2 mL can be given as a single injection or infusion into a vein. It can also be administered through a fine needle into the tissue under the skin.

Oxycodone Juno infusion 50 mg in 1 mL can only be given as an infusion into a vein or an infusion into the tissue under the skin.

Your doctor will decide the most appropriate way to administer Oxycodone Juno injection or infusion. Using this medicine in a manner other than that prescribed by your doctor can be harmful to your health.

When it is given

You should be given Oxycodone Juno injection or infusion as directed by your doctor.

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

How long it is given for

You should be given this medicine for as long as directed by your doctor.

You should not be given Oxycodone Juno infusion 50 mg in 1 mL for more than 4 consecutive weeks.

If you stop having this medicine suddenly, the pain may worsen and you may experience withdrawal symptoms such as:

  • body aches
  • loss of appetite, nausea, stomach cramps or diarrhoea
  • fast heart rate
  • sneezing or runny nose
  • chills, tremors, shivering or fever
  • trouble sleeping
  • increased sweating and yawning
  • weakness
  • nervousness or restlessness.

If you are given too much (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (Australia: telephone 13 11 26) for advice or go to Accident and Emergency at your nearest hospital if you are not already in hospital, if you think you or anyone else may have been given too much Oxycodone Juno injection or infusion.

Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Keep telephone numbers for these places handy.

If someone is given an overdose they may experience difficulties in breathing, become drowsy and tired, lack muscle tone, have cold or clammy skin, have constricted pupils, have very low blood pressure or slow heart rate, and possibly may even become unconscious or die.

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

While you are given Oxycodone Juno injection or Infusion

Things you must do

Before you start on a new medicine, remind your doctor and pharmacist that you are being given Oxycodone Juno injection or infusion.

Tell any other doctors, dentists and pharmacists who treat you that you are having this medicine.

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

It may affect other medicines used during surgery.

If you become pregnant while being given this medicine, tell your doctor immediately.

Keep all of your doctor's appointments so that your progress can be checked.

Tell your doctor if your pain is getting worse. Always discuss any problems or difficulties you have while you are being treated with Oxycodone Juno injection or infusion. Tolerance to oxycodone may develop which means that the effect of the medicine may decrease. If this happens, your doctor may review the dose so that you get adequate pain relief.

Things you must not do

Do not drink alcohol while you are being given this medicine.

Drinking alcohol whilst using Oxycodone Juno injection or infusion may make you feel more sleepy and increase the risk of serious side effects, such as shallow breathing with the risk of stopping breathing and loss of consciousness.

Do not use Oxycodone Juno injection or infusion to treat any other complaint unless your doctor tells you to.

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

Oxycodone Juno injection or infusion is intended for use in one patient only.

Do not stop using the medicine, exceed the dose recommended or change the dosage without checking with your doctor.

Over time your body may become used to oxycodone so if it is stopped suddenly, the pain may worsen and you may have unwanted side effects such as withdrawal symptoms. This is called physical dependence. If you need to stop having this medicine, your doctor will gradually reduce the amount each day, if possible, before stopping the medicine completely.

Things to be careful of

Do not drive or operate machinery until you know how Oxycodone Juno injection or infusion affects you.

Oxycodone Juno injection or infusion may cause drowsiness, dizziness, hallucinations, disorientation, blurred vision or other vision problems or may affect alertness. If you are affected, you should not drive or operate machinery. Discuss these effects with your doctor.

Be careful if you are elderly, unwell or taking other medicines.

Some people may experience side effects such as drowsiness, confusion, dizziness and unsteadiness, which may increase the risk of a fall.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly.

Standing up slowly will help your body get used to the change in position and blood pressure. If this problem continues or gets worse, talk to your doctor.

Tell your doctor if you suffer from nausea or vomiting when having Oxycodone Juno injection or infusion.

Your doctor may prescribe some medicine to help you stop vomiting.

Tell your doctor if having Oxycodone Juno injection or infusion causes constipation.

Your doctor can advise you about your diet, the proper use of laxatives and suitable exercise you can do to help you manage this.

Tell your doctor if you find that you cannot concentrate or that you feel more sleepy than normal when you are being treated with Oxycodone Juno injection or infusion or when the dose is increased.

This feeling should wear off after a few days.

There is potential for abuse of oxycodone and the development of addiction to oxycodone. It is important that you discuss this issue with your doctor.

Side effects

All medicines may have some unwanted side effects. Sometimes they are serious but most of the time they are not. As for many other medicines of this type, that is opioid analgesics, many side effects tend to reduce over time, with the exception of constipation. This means that the longer you have this medicine, the less it may cause problems for you. Your doctor has weighed the risks of this medicine against the benefits they expect it will have for you.

Do not be alarmed by this list of possible side effects.

Not everybody experiences them.

Tell your doctor as soon as possible if you do not feel well while you are having Oxycodone Juno injection or infusion.

This medicine helps most people with moderate to severe pain, but it may have unwanted side effects in a few people. Other side effects not listed here may also occur in some people.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • mild abdominal symptoms such as diarrhoea, feeling sick (nausea), decreased appetite, constipation or excessive wind
  • dry mouth, hiccups or trouble swallowing
  • excessive sweating
  • feeling anxious or nervous or have trouble sleeping
  • trouble with your balance (vertigo)
  • looking pale or feeling excessively tired
  • new problems with your eyesight
  • skin rash, itching, chills or fever
  • unusually reduced or slow body movements
  • muscle problems such as spasms, twitching or tremors
  • swelling of legs or ankles
  • pain and sensitivity at the injection site
  • absence of menstrual periods
  • erectile dysfunction
  • decreased sexual drive.

Tell your doctor as soon as possible if you notice any of the following and they worry you:

  • stomach discomfort, vomiting, indigestion or abdominal pain
  • abnormal thinking, changes in mood or feeling deep sadness
  • drowsiness, fainting or dizziness especially when standing up
  • slow or noticeable heartbeats
  • headache, confusion, hallucinations, disorientation, sleepiness or impaired consciousness
  • unusual weakness or loss of strength
  • fatigue, feeling of tiredness, drowsiness or lack of energy
  • changes in passing urine such as the volume passed, pain or feeling the need to urinate urgently or difficulty passing urine

The above list includes serious side effects that may require medical treatment.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at the nearest hospital:

  • your breathing slows or weakens
  • you have an allergic reaction: shortness of breath, wheezing, shallow or difficult breathing; swelling of the face, lips, tongue, throat or other parts of the body; rash, itching or hives on the skin
  • seizures, fits or convulsions
  • fast or irregular heartbeats
  • chest pain or chest tightness.

The above list includes very serious side effects. You may need urgent medical attention or hospitalization.

When seeking medical attention take this leaflet and any remaining medicine with you to show the doctor.

After having it

Storage

Oxycodone Juno injection or infusion should be given immediately after opening the ampoule. Once opened, any unused portion should be discarded.

If you are being given Oxycodone Juno injection or infusion in hospital, unopened ampoules will be stored in the pharmacy or on the ward.

If you have some of this medicine at home, keep the unopened ampoules in a cool, dry place where the temperature stays below 30°C and protected from light.

Do not store it or any other medicine in the bathroom, near a sink or on a window sill.

Do not leave it in the car.

Heat and damp can destroy some medicines.

Keep it where children cannot reach it.

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

Disposal

If your doctor tells you to stop having this medicine or the medicine has passed the expiry date, ask your pharmacist how to dispose of medicines no longer required.

Product description

What it looks like

Oxycodone Juno® solution for injection or infusion is available in glass ampoules containing a clear, colourless solution. It is available in two presentations:

10 mg in 1 mL
20 mg in 2 mL.

Oxycodone Juno® solution for infusion is available in glass ampoules containing a clear, colourless solution. It is available in one presentation:

50 mg in 1 mL.

Oxycodone Juno® solution for injection or infusion and Oxycodone Juno® solution for infusion are supplied in packs of 5 ampoules.

Ingredients

Active ingredient:

1 mL of Oxycodone Juno solution for injection or infusion 10 mg in 1 mL and 20 mg in 2 mL both contain 10 mg of oxycodone hydrochloride.

1 mL of Oxycodone Juno solution for infusion 50 mg in 1 mL contains 50 mg of oxycodone hydrochloride.

Inactive ingredients:

  • citric acid monohydrate
  • sodium citrate
  • sodium chloride
  • hydrochloric acid
  • sodium hydroxide
  • water for injections.

This medicine does not contain lactose, sucrose, gluten, tartrazine or other azo dyes.

Manufacturer / Sponsor

Oxycodone Juno solution for injection or infusion and OXYCODONE JUNO solution for infusion are supplied in Australia by:

Juno Pharmaceuticals Pty Ltd
Level 2, 6 Bond Street,
South Yarra, VIC – 3141.

This leaflet was prepared in August 2016.

Doc ID:117.JU.M.1.0

BRAND INFORMATION

Brand name

Oxycodone Juno Solution for injection or infusion

Active ingredient

Oxycodone hydrochloride

Schedule

S8

 

1 Name of Medicine

Oxycodone hydrochloride.

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.


CAS number.

124-90-3.

2 Qualitative and Quantitative Composition

Oxycodone Juno 10 mg/1 mL solution for injection ampoule contains 10 mg of oxycodone hydrochloride.
Oxycodone Juno 20 mg/2 mL solution for injection ampoule contains 20 mg of oxycodone hydrochloride.
Oxycodone Juno 200 mg/20 mL solution for injection ampoule contains 200 mg of oxycodone hydrochloride.
Oxycodone Juno 50 mg/1 mL solution for infusion ampoule contains 50 mg of oxycodone hydrochloride.
The inactive ingredients in Oxycodone Juno solution for injection or infusion are: citric acid monohydrate, sodium citrate, sodium chloride, hydrochloric acid, sodium hydroxide and water for injections.

3 Pharmaceutical Form

10 mg in 1 mL is available as solution for injection ampoule.
20 mg in 2 mL is available as solution for injection ampoule.
50 mg in 1 mL is available as solution for infusion ampoule.
200 mg in 20 mL is available as solution for injection ampoule.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Oxycodone is a full opioid agonist with no antagonist properties whose principal therapeutic action is analgesia. It has affinity for kappa, mu and delta opiate receptors in the brain and spinal cord. Oxycodone is similar to morphine in its action. Other pharmacological actions of oxycodone are in the CNS (respiratory depression, antitussive, anxiolytic, sedative and miosis), smooth muscle (constipation, reduction in gastric, biliary and pancreatic secretions, spasm of sphincter of Oddi and transient elevations in serum amylase) and cardiovascular system (release of histamine and/or peripheral vasodilation, possibly causing pruritus, flushing, red eyes, sweating and/or orthostatic hypotension).

Clinical trials.

Oxycodone Juno solution for injection or infusion 10 mg in 1 mL.

A randomised, double-blind, parallel group study was performed to compare the tolerability, safety and efficacy of IV oxycodone with IV morphine in patients using patient-controlled analgesia (PCA) for acute postoperative pain. The intention to treat and safety populations included 133 patients (64 oxycodone, 69 morphine); 117 patients completed, 56 on oxycodone and 61 on morphine. Oxycodone 10 mg/mL or morphine solution for injection was diluted to 1 mg/mL with 0.9% saline, and 2 mg IV bolus doses were used during stabilisation. The PCA machine delivered bolus doses of 1 mg on demand, with a 5 minute lockout. The treatment duration was intended to be 24-72 hours.
The primary efficacy endpoint of the intensity of pain on movement or deep breathing at 24 hours post-operatively, using the BS-11 pain scores was 4.6 ± 2.6 for oxycodone and 4.1 ± 2.0 for morphine with a pain intensity difference of 0.55 (95% CI: -0.37 to 1.48). The 95% CI for the treatment difference was within the established equivalence limits (-1.5 to 1.5) (see Table 1).
There was no significant difference in the median drug use, which was 69.0 mg (12-336 mg) for oxycodone and 54.0 mg (7-212 mg) for morphine in the PP population, and similar in the ITT population. The common adverse drug reactions were all known opioid side-effects, but respiratory depression was uncommon. Further details are provided, see Section 4.8 Adverse Effects (Undesirable Effects).

5.2 Pharmacokinetic Properties

Absorption.

The Tmax for subcutaneous administration was 0.25-0.5 hours. Considerable inter-individual variability was seen in pharmacokinetic studies.
Pharmacokinetic studies with Oxycodone Juno solution for injection or infusion in healthy subjects demonstrated an equivalent availability of oxycodone by intravenous (IV) and subcutaneous (SC) routes, when administered as a single bolus dose or continuous infusion over 8 hours. Following absorption, oxycodone is distributed throughout the entire body. As expected, the Cmax for subcutaneous bolus was lower than for intravenous administration.

Distribution.

Approximately 45% is bound to plasma proteins. The plasma concentrations are only minimally affected by age, being 15% greater in the elderly compared with young subjects.

Metabolism and excretion.

Oxycodone has an elimination half-life of approximately 3 hours and is metabolised principally in the liver to noroxycodone and oxymorphone. Oxymorphone has some analgesic activity but is present in plasma in low concentrations and is not considered to contribute to oxycodone’s pharmacological effect.
Oxycodone hydrochloride is metabolised in the liver to form noroxycodone, oxymorphone, noroxymorphone, 6 α and β oxycodol and conjugated glucuronides. CYP3A4 and CYP2D6 are involved in the formation of noroxycodone and oxymorphone, respectively (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). The contribution of these metabolites to the analgesic effect is insignificant.
CYP2D6 is expressed as two phenotypes, extensive and poor metabolisers. Poor metabolisers, constituting about 5-10% of the White population, may have increased plasma concentrations of oxycodone because of the decreased oxidation by CYP2D6 and therefore a lower dosage may be needed. See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.
Patients with mild to severe hepatic or renal dysfunction may have an increase in elimination half-life compared with normal subjects, and therefore, may have higher plasma concentrations of oxycodone and noroxycodone, and lower concentrations of oxymorphone compared with normal subjects. This may be accompanied by an increase in drug effects. Considerable inter-individual variability may be seen in these patients.

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.

Studies of oxycodone in animals to evaluate the carcinogenic potential have not been conducted.

4 Clinical Particulars

4.1 Therapeutic Indications

The management of opioid-responsive moderate to severe pain.

4.3 Contraindications

Hypersensitivity to opioids or any of the constituents of Oxycodone Juno solution for injection or infusion, acute respiratory depression, cor pulmonale, cardiac arrhythmias, acute asthma or other obstructive airways disease, paralytic ileus, suspected surgical abdomen, severe renal impairment (creatinine clearance < 10 mL/min), moderate to severe hepatic impairment (see Section 4.4 Special Warnings and Precautions for Use, Special risk groups), acute abdominal pain, chronic constipation, delayed gastric emptying, acute alcoholism, coma, brain tumour, increased cerebrospinal or intracranial pressure, head injury (due to risk of raised intracranial pressure), severe CNS depression, convulsive disorders, delirium tremens, hypercarbia, concurrent administration of monoamine oxidase inhibitors or within 2 weeks of discontinuation of their use, anxiety states under the influence of alcohol or hypnotics and pregnancy.

4.4 Special Warnings and Precautions for Use

The major risk of opioid excess is respiratory depression, including subclinical respiratory depression. As with all opioids, a reduction in dosage may be advisable in hypothyroidism. Use with caution in opioid-dependent patients and in patients with hypotension, hypovolaemia, diseases of the biliary tract, pancreatitis, inflammatory bowel disorders, prostatic hypertrophy, adrenocortical insufficiency (Addison’s disease), toxic psychosis, chronic pulmonary, renal and hepatic disease, myxoedema and debilitated elderly or infirm patients or patients taking benzodiazepines, other CNS depressants (including alcohol) or MAO inhibitors. As with all opioid preparations, patients who are to undergo cordotomy or other pain-relieving neural blockade procedures should not receive Oxycodone Juno solution for injection or infusion for 6 hours before surgery. As with all opioid preparations, Oxycodone Juno solution for injection or infusion should be used with caution following abdominal 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, Oxycodone Juno solution for injection or infusion should be discontinued immediately. Oxycodone Juno solution for injection or infusion should be used with caution pre- or intra-operatively and within the first 12-24 hours post-operatively. Oxycodone Juno solution for infusion 50 mg/mL should not be used for more than 4 weeks consecutively.
Hyperalgesia that will not respond to a further dose increase of oxycodone may very rarely occur in particular at high doses. An oxycodone dose reduction or change in opioid may be required.
Opioids, such as oxycodone hydrochloride, 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.

Drug dependence.

As with other opioids, tolerance and physical dependence tend to develop upon repeated administration of oxycodone. There is potential for abuse of the drug and for development of strong psychological dependence. Oxycodone Juno solution for injection or infusion should therefore be prescribed and handled with a high degree of caution appropriate to the use of a drug with strong abuse potential.
In the absence of a clear indication for a strong opioid analgesic, drug-seeking behaviour must be suspected and resisted, particularly in individuals with a history of, or propensity for, drug abuse. Withdrawal symptoms may occur following abrupt discontinuation of oxycodone therapy or upon administration of an opioid antagonist. Therefore, patients on prolonged therapy should be withdrawn gradually from the drug if it is no longer required.
Oxycodone should be used with caution and under close supervision in patients with pain not due to malignancy who have a prior history of substance abuse. However, in such cases, prior psychological assessment is essential and the prescribing doctor should consider that the benefit of treatment outweighs the risk of abuse.

Special risk groups.

Use in renal and hepatic impairment.

In renal and hepatic impairment, the administration of Oxycodone Juno solution for injection or infusion does not result in significant levels of active metabolites. However, the plasma concentration of oxycodone in this patient population may be increased compared with patients having normal renal or hepatic function. Therefore, initiation of dosing in patients with renal impairment (CLcr < 60 mL/min) or hepatic impairment should be reduced to 1/3 to ½ of the usual dose with cautious titration.

Use in the elderly.

The plasma concentrations of oxycodone are only nominally affected by age, being approximately 15% greater in elderly as compared with young subjects. There were no differences in adverse event reporting between young and elderly subjects.

Paediatric use.

Oxycodone Juno solution for injection or infusion should not be used in patients under 18 years as there are no data on use in children under 18 years of age. (see Section 4.2 Dose and Method of Administration, Adults, elderly and children over 18 years).

Use in elderly, debilitated patients.

As with other opioid initiation and titration, doses in elderly patients who are debilitated should be reduced to 1/3 to ½ of the usual doses.

Gender.

Female subjects have, on average, plasma oxycodone concentrations up to 25% higher than males on a body weight adjusted basis. The reason for this difference is unknown. There were no significant male/female differences detected for efficacy or adverse events in clinical trials.

Effect on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Anticholinergic agents.

Concurrent use with oxycodone with anticholinergics or medications with anticholinergic activity (e.g. tricyclic antidepressants, antihistamines, antipsychotics, muscle relaxants, anti-Parkinson medications) may result in increased anticholinergic adverse effects, including an increased risk of severe constipation and/or urinary retention.

Antihypertensive agents.

Hypotensive effects of these medications may be potentiated when used concurrently with oxycodone, leading to an increased risk of orthostatic hypotension.

CNS depressants (including non-benzodiazepines sedatives or hypnotics, general anaesthetics, phenothiazines, other tranquillisers, alcohol, other opioids, benzodiazepines and neuroleptic drugs, etc.).

Concurrent use with oxycodone may result in increased respiratory depression, hypotension, profound sedation, death or coma. Caution is recommended and the dosage of one or both agents should be reduced. Intake of alcoholic beverages while being treated with Oxycodone Juno solution for injection or infusion should be avoided because this may lead to more frequent undesirable effects such as somnolence and respiratory depression. Oxycodone hydrochloride containing products should be avoided in patients with a history of or present alcohol, drug or medicines abuse.

Coumarin derivatives.

Although there is little substantiating evidence, opiate agonists have been reported to potentiate the anticoagulant activity of coumarin derivatives.

CYP3A4 and CYP2D6 inducers and inhibitors.

Oxycodone is metabolised in part via the CYP2D6 and CYP3A4 pathways. The activities of these metabolic pathways may be inhibited or induced by various co-administered drugs or dietary elements, which may alter plasma concentrations. Oxycodone doses may need to be adjusted accordingly. Drugs that inhibit CYP2D6 activity, such as paroxetine and quinidine, may cause decreased clearance of oxycodone which could lead to an increase in oxycodone plasma concentrations. Concurrent administration of quinidine does not alter the pharmacodynamic effects of oxycodone. CYP3A4 inhibitors such as macrolide antibiotics (e.g. clarithromycin), azole antifungal agents (e.g. ketoconazole), protease inhibitors (e.g. ritonavir) and grapefruit juice may cause decreased clearance of oxycodone which could lead to an increase in oxycodone plasma concentrations. Oxycodone metabolism may be blocked by a variety of drugs (e.g. cimetidine, certain cardiovascular drugs, fluoxetine and other antidepressants and erythromycin), although such blockade has not yet been shown to be of clinical significance with Oxycodone Juno solution for injection or infusion.
CYP3A4 inducers, such as rifampin, carbamazepine, phenytoin and St. John's wort, may induce the metabolism of oxycodone and cause increased clearance of the drug, resulting in a decrease in oxycodone plasma concentrations. Oxycodone did not inhibit the activity of P450 isozymes 2D6, 3A4, 1A2, 2A6, 2C19 or 2E1 in human liver microsomes in vitro. Non-clinical data in vitro and in vivo indicate that oxycodone can act as a P-glycoprotein substrate and can induce over-expression of P-glycoprotein in rats.

Metoclopramide.

Concurrent use with oxycodone may antagonise the effects of metoclopramide on gastrointestinal motility.

Monoamine oxidase inhibitors (MAOIs).

Non-selective MAOIs intensify the effects of opioid drugs which can cause anxiety, confusion and significant respiratory depression. Severe and sometimes fatal reactions have occurred in patients concurrently administered MAOIs and pethidine. Oxycodone should not be given to patients taking non-selective MAOIs or within 14 days of stopping such treatment. As it is unknown whether there is an interaction between selective MAOIs (e.g. selegiline) and oxycodone, caution is advised with this drug combination.

Neuromuscular blocking agents.

Oxycodone may enhance the effects of neuromuscular blocking agents resulting in increased respiratory depression.

Opioid agonist analgesics (including morphine, pethidine).

Additive CNS depressant, respiratory depressant and hypotensive effects may occur if two or more opioid agonist analgesics are used concurrently.

Opioid agonist-antagonist analgesics (including pentazocine, butorphanol, buprenorphine).

Mixed agonist/antagonist analgesics may reduce the analgesic effect of oxycodone and/or may precipitate withdrawal symptoms.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In reproductive toxicology studies, no evidence of impaired fertility was seen in male or female rats at oxycodone doses of 8 mg/kg/day, with estimated exposure (plasma AUC) equivalent to 8 mg/day in men and 17 mg/day in women.
Despite these fertility studies in animals, prolonged use of opioids may result in impairment of reproductive function, including fertility and sexual dysfunction in both sexes, and irregular menses in women.
(Category C)
Australian characterisation of pregnancy definition: 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 cause of malformations. These effects may be reversible.
Oxycodone used during pregnancy or labour may cause withdrawal symptoms and/or respiratory depression in the newborn infant. Oral administration of oxycodone during the period of organogenesis did not elicit teratogenicity or embryofoetal toxicity in rats or rabbits at doses up to 8 mg/kg/day in rats (equivalent to 17 mg/day in women, based on estimated plasma AUC values) or 125 mg/kg/day in rabbits.
Oral administration of oxycodone to rats from early gestation to weaning did not affect postnatal development parameters at doses up to 6 mg/kg/day (equivalent to 9 mg/day in women, based on estimated AUC values). In a study designed specifically to investigate the effect of prenatal oxycodone on the hypothalamic-pituitary-adrenal axis in adolescent rats, intravenous administration of oxycodone 0.8 mg/kg/day (equivalent to 11 mg/day in pregnant women, based on estimated AUC values) had no effect on the corticosterone response, but delayed and enhanced the peak ACTH response to corticotrophin releasing hormone in males, but not females. The clinical significance of this observation is unknown.
There are no adequate and well-controlled studies with oxycodone in pregnant women. Because animal reproduction studies are not always predictive of human responses, oxycodone should not be used during pregnancy unless clearly needed. Prolonged use of oxycodone during pregnancy can result in neonatial opioid withdrawal syndrome. Oxycodone is not recommended for use in women during or immediately prior to labour. Infants born to mothers who have received opioids during pregnancy should be monitored for respiratory depression.
Oxycodone accumulates in human milk, with a median maternal milk:plasma ratio of 3:1 recorded in one study. Oxycodone (7.5 nanogram/mL) was detected in the plasma of one of forty-one infants 72 hours after Caesarean section. Opioids may cause respiratory depression in the newborn and withdrawal symptoms can occur in breastfeeding infants when maternal administration of an opioid analgesic is stopped. Oxycodone Juno solution for injection or infusion should not be used in breastfeeding mothers unless the benefits outweigh the risks. Breastfed infants should be monitored for respiratory depression, sedation, poor attachment and gastrointestinal signs.

4.8 Adverse Effects (Undesirable Effects)

Adverse drug reactions are typical of full opioid agonists, and tend to reduce with time, with the exception of constipation. Anticipation of adverse drug reactions and appropriate patient management can improve acceptability.

Injectable formulation.

In a clinical trial where intravenous oxycodone was delivered via patient-controlled analgesia, 50 of 64 (78%) patients on oxycodone had at least one adverse drug reaction rated treatment-related or not determined. The very common adverse drug reactions included nausea (50%), vomiting (17%) and pruritus (14%), and the more common reactions included headache (6%), constipation (5%) and insomnia (5%). All of the adverse drug reactions were mild or moderate in intensity, except for one report of vomiting and one of nausea which were rated severe. One treatment-related serious adverse event (abdominal pain caused by postoperative constipation) was noted 17 days after intravenous oxycodone was ceased. In two smaller trials, the very common adverse reactions included headache, dizziness and somnolence.
Drowsiness often abates after a few days, and nausea and vomiting after use for a sustained period. Spasms in the bile duct and urinary tract may arise in predisposed individuals. The respiratory depressive effect is dose dependent.

Cardiac disorders.

Common: tachycardia.
Uncommon: palpitations (as part of withdrawal syndrome).

Ear and labyrinth disorders.

Common: vertigo.

Endocrine disorders.

Common: increased ADH release.

Eye disorders.

Common: miosis, visual impairment.

Gastrointestinal disorders.

Very common: nausea, vomiting, constipation.
Common: abdominal pain, diarrhoea, dry mouth, dyspepsia, flatulence, hiccup.
Uncommon: dental caries, dysphagia, eructation, gastrointestinal disorder, ileus, flatulence.

General disorders and administration site conditions.

Common: asthenia, fatigue, chills, fatigue, hot/warm, injection site hypersensitivity/pain, oedema, pain, pallor.
Uncommon: drug tolerance, drug withdrawal syndrome, malaise, peripheral oedema, thirst.
Not known: drug withdrawal syndrome neonatal.

Hepatobiliary disorders.

Uncommon: biliary spasm, cholestasis, hepatic enzyme increased.

Immune system disorders.

Uncommon: anaphylactic reaction, anaphylactoid reaction, hypersensitivity.

Metabolism and nutrition disorders.

Common: decreased appetite.
Uncommon: dehydration.

Nervous system disorders.

Very common: dizziness, drowsiness, headache, somnolence.
Common: hypokinesia, stupor, tremor, lethargy.
Uncommon: amnesia, convulsion, grogginess, hypertonia, hypoaesthesia, muscle contractions involuntary, paraesthesia, speech disorder, syncope, dysgeusia (taste perversion).
Not Known: hyperalgesia.

Psychiatric disorders.

Very common: euphoric mood.
Common: anxiety, confusional state, disorientation, insomnia, nervousness, thinking abnormal, depression.
Uncommon: affect lability, agitation, drug dependence, dysphoria, hallucination, libido decreased.
Not known: aggression.

Renal and urinary disorders.

Common: urinary retention.
Uncommon: urinary spasm.

Reproductive system and breast disorders.

Uncommon: amenorrhoea, erectile dysfunction, hypogonadism.

Respiratory, thoracic and mediastinal disorders.

Common: dyspnoea, hyperventilation.
Uncommon: bronchoconstriction, respiratory depression.

Skin and subcutaneous tissue disorders.

Very common: pruritus.
Common: hyperhidrosis, rash.
Uncommon: dry skin, urticaria.

Vascular disorders.

Common: hypotension, vasodilatation.
Uncommon: orthostatic hypotension.

Key.

Very common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1000 to < 1/100); Rare (≥ 1/10,000 to < 1/1000); Very rare (< 1/10,000); Not known (cannot be estimated from the available data).

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.

4.2 Dose and Method of Administration

Non-malignant pain.

In common with other strong opioids, the need for continued treatment should be assessed at regular intervals.

Adults, elderly and children over 18 years.

Prior to initiation and titration of doses, see Section 4.4 Special Warnings and Precautions for Use for information on special risk groups such as females and the elderly. The lowest dose should be administered with careful titration to pain control. Oxycodone Juno solution for injection or infusion should not be used in patients under 18 years as there are no data on use in children under 18 years of age.

Routes of administration.

Oxycodone Juno solution for injection or infusion 10 mg in 1 mL and 20 mg in 2 mL.

Intravenous injection or infusion, and subcutaneous injection or infusion.

Oxycodone Juno solution for infusion 50 mg in 1 mL.

Intravenous infusion and subcutaneous infusion, suitable for use in a palliative care setting.

Posology.

The dose should be adjusted according to the severity of pain, the total condition of the patient and previous or concurrent medication.

Adults over 18 years.

Oxycodone Juno solution for injection or infusion 10 mg in 1 mL and 20 mg in 2 mL.

The following starting doses are recommended for the 10 mg in 1 mL and 20 mg in 2 mL solution for injections, although the starting dose will vary with age, medical status, surgery, pre-existing opioid tolerance, concomitant medications, individual tolerability, severity of pain and the indication, and may require subsequent dosage adjustment. A gradual increase in dose may be required if analgesia is inadequate or if pain severity increases.

IV (injection).

Dilute to 1 mg/mL in 0.9% saline, 5% dextrose or water for injections.
To establish analgesia, administer an intravenous bolus dose of 1 to 5 mg slowly over 1-2 minutes. Incremental bolus doses may be required at 5-10 min intervals, with monitoring of the patient. Previous studies have indicated that higher single bolus doses (5-15 mg) oxycodone have been associated with significant sedation and respiratory depression.
For maintenance analgesia, doses should not be administered more frequently than every 4 hours.

IV (infusion).

Dilute to 1 mg/mL in 0.9% saline, 5% dextrose or water for injections. A starting dose of 2 mg/hour is recommended.

IV (PCA).

Dilute to 1 mg/mL in 0.9% saline, 5% dextrose or water for injections. A starting PCA bolus dose of up to 0.03 mg/kg (e.g. 1-2 mg per 70 kg) should be administered with a minimum lock-out time of 5 minutes.

SC (injection).

Use as 10 mg/mL concentration. A starting dose of 5 to 10 mg is recommended, depending on age and medical status, repeated at 4-hourly intervals as required.

SC (infusion).

Dilute in 0.9% saline, 5% dextrose or water for injections if required. For non-surgical pain in palliative care in opioid-tolerant patients, titrate gradually according to pain control.

Oxycodone Juno solution for infusion 50 mg in 1 mL.

The use of Oxycodone Juno solution for infusion 50 mg in 1 mL is indicated for opioid-tolerant patients in a palliative care setting. The following starting doses are recommended, although the starting dose will vary with age, medical status, surgery, pre-existing opioid tolerance, concomitant medications, individual tolerability, severity of pain and the indication, and may require subsequent dosage adjustment. A gradual increase in dose may be required if analgesia is inadequate or if pain severity increases. Oxycodone Juno 50 mg in 1 mL solution for infusion should not be used for more than 4 consecutive weeks.

IV (infusion).

Dilute to 1 mg/mL in 0.9% saline, 5% dextrose or water for injections. A starting dose of 2 mg/hour is recommended.

IV (PCA).

Dilute to 1 mg/mL in 0.9% saline, 5% dextrose or water for injections. A starting PCA bolus dose of up to 0.03 mg/kg (e.g. 1-2 mg per 70 kg) should be administered with a minimum lock-out time of 5 minutes.

SC (infusion).

Dilute in 0.9% saline, 5% dextrose or water for injections. Continuous subcutaneous infusion of a strong opioid is typically commenced via a syringe driver apparatus.

Transferring patients from oral to parenteral oxycodone.

The dose should be based on the following ratio: 2 mg of oral oxycodone is approximately equivalent to 1 mg of parenteral oxycodone. The approximate conversion ratio between oral and parenteral oxycodone is 2:1 (oral:parenteral), based on an oral liquid bioavailability of 46% (90% CI 41% to 51%). It is emphasised that this is a guide to the required dose only. Inter- patient variability requires that each patient is carefully titrated to the appropriate dose. For cancer patients transferring from oral oxycodone, or rotating from other opioid infusions, dosage requirements may be higher.

Transferring patients from IV morphine to IV oxycodone.

The dose should be based on the following ratio: 1 mg of IV oxycodone is approximately equivalent to 1 mg of IV morphine. The approximate conversion ratio between IV oxycodone and IV morphine is 1:1, based on the PCA study described, see Section 5.1 Pharmacodynamic Properties, Clinical trials. It is emphasised that this is a guide to the required dose only. Inter-patient variability requires that each patient is carefully titrated to the appropriate dose. For cancer patients transferring from oral oxycodone, or rotating from other opioid injections or infusions, the dosage requirements may be higher.

Elderly.

Elderly patients should be treated with caution. The lowest dose should be administered with careful titration to pain control.
As with other opioid initiation and titration, doses in elderly patients who are debilitated should be reduced to 1/3 to ½ of the usual doses.

Adults with mild to moderate renal impairment and mild hepatic impairment.

The plasma concentration in this patient population may be increased. Therefore, dose initiation should follow a conservative approach with careful titration to pain control (see Section 4.4 Special Warnings and Precautions for Use).
As with other opioid initiation and titration, doses in patients with renal impairment (CLcr < 60 mL/min) or hepatic impairment should be reduced to 1/3 to ½ of the usual doses.

Use in non-malignant pain.

Opioids are not first-line therapy for chronic non-malignant pain, nor are they recommended as the only treatment. The need for continued treatment in non-malignant pain should be assessed at regular intervals (see Section 4.4 Special Warnings and Precautions for Use, Drug dependence).

Cessation of therapy.

When a patient no longer requires therapy with oxycodone, it is advisable to reduce the daily dose gradually to minimise or prevent symptoms of withdrawal.

Instructions for storage and handling.

The solution for injection or infusion should be given immediately after opening the ampoule. The diluted solution should be used immediately after dilution. Once opened, any unused portion should be discarded. Inappropriate handling of the undiluted solution after opening of the original ampoule, or of the diluted solutions may compromise the sterility of the product. Oxycodone Juno solution for injection or infusion is for single use in one patient only.

4.7 Effects on Ability to Drive and Use Machines

Oxycodone may modify patients' reactions to a varying extent depending on the dosage and individual susceptibility. If affected, patients should not drive or operate machinery.

4.9 Overdose

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, hypotension, pulmonary oedema, and death. Severe overdose may result in apnoea, pulmonary oedema, circulatory collapse and death.

Treatment.

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 inter-individual 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).

7 Medicine Schedule (Poisons Standard)

S8.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Oxycodone Juno solution for injection or infusion is formulated at acidic pH and is likely to be incompatible with alkaline pH formulations such as fluorouracil (5-FU) which may lead to precipitation. In addition, Oxycodone Juno solution for injection or infusion has been shown to be chemically incompatible with prochlorperazine.
It is recommended that Oxycodone Juno solution for injection or infusion should not be administered in combination with other parenteral formulations unless there is compatibility data to support the combination.

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

Oxycodone Juno solution for injection or infusion should be stored below 30°C and protected from light.

6.5 Nature and Contents of Container

Clear glass ampoules containing the following strengths of oxycodone hydrochloride:
10 mg in 1 mL and 20 mg in 2 mL in packs of 5 ampoules;
50 mg in 1 mL in packs of 5 ampoules;
200 mg in 20 mL in packs of 4 ampoules.
Not all presentations may be marketed.

6.6 Special Precautions for Disposal

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

Summary Table of Changes