Consumer medicine information

OxyContin Tablets

Oxycodone hydrochloride

BRAND INFORMATION

Brand name

OxyContin

Active ingredient

Oxycodone hydrochloride

Schedule

S8

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using OxyContin Tablets.

What is in this leaflet

This leaflet answers some common questions about OxyContin tablets.

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 taking this medicine against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What OxyContin tablets are taken for

OxyContin tablets contain oxycodone hydrochloride. Oxycodone belongs to a group of medicines called opioid analgesics.

OxyContin tablets are used to relieve severe pain when other forms of treatment have failed or are otherwise inappropriate to provide sufficient management of pain.

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 taking OxyContin tablets. Taking it may result in physical dependence. Physical dependence means that you may experience withdrawal symptoms if you stop taking OxyContin tablets suddenly, so it is important to take it exactly as directed by your doctor.

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

Before you take it

Long-term use of OxyContin tablets may result in a decrease in sex hormone levels which may affect sperm production in men and the menstrual cycles in females. Talk to your doctor if you have concerns.

When you must not take it

Do not take OxyContin tablets 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 heartbeats or changes in the way the heart beats
  • have heart disease due to long term 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 from convulsions, fits or seizures
  • have a head injury, a brain tumour or have raised pressure within the head, brain or spinal cord
  • have sudden, severe abdominal pain
  • have a condition where your stomach empties more slowly than it should or any condition that obstructs the stomach/bowel or affects bowel transit (movement of food or ingested material along the bowel)
  • have swallowing difficulties or narrowing of the oesophagus
  • have severe liver or kidney disease
  • are about to have an operation (including surgery on your spine for pain relief in the next 24 hours) or have had an operation within the last 24 hours
  • take a medicine for depression called a 'monoamine oxidase inhibitor' or have taken any in the last two weeks.

Do not take OxyContin tablets if you are allergic to oxycodone, opioid painkillers, or any of the ingredients listed at the end of this leaflet.

Do not take this medicine after the expiry date (EXP) printed on the pack. If you take it after the expiry date has passed, it may not work very well.

Do not take it if the packaging is torn or shows signs of tampering.

Do not give this medicine to a child younger than 12 years of age. Safety and effectiveness in children younger than 12 years of age have not been established.

Before you start to take 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:

  • Have sleep apnoea (temporarily stopping breathing while you sleep)
  • 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 or recent abdominal surgery
  • diverticulitis (inflammation of bowel wall)
  • oesophageal, stomach or intestinal disorders (including cancer in these areas) resulting in narrowing of the oesophagus, stomach or intestines
  • 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.

Pregnancy and breastfeeding

This medicine is not recommended to be taken during labour.

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

Tell your doctor if you are breastfeeding or planning to breastfeed.

Oxycodone can pass into the breast milk and can affect the baby.

Your doctor can discuss with you the risks involved.

If you have not told your doctor about any of the above, tell them before you take any OxyContin tablets.

Do not take this medicine if you are pregnant or intend to become pregnant whilst taking this medicine.

Like most medicines of this kind, OxyContin tablets are not recommended to be taken during pregnancy. Your doctor will discuss the risks of taking it if you are pregnant.

Addiction
You can become addicted to OxyContin even if you take it exactly as prescribed. OxyContin 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 taking OxyContin. Taking it may result in physical dependence. Physical dependence means that you may experience withdrawal symptoms if you stop taking OxyContin suddenly, so it is important to take it exactly as directed by your doctor.

Tolerance
Tolerance to OxyContin 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 taking 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.

Taking other medicines

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

Some medicines and OxyContin tablets 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 OxyContin tablets are taken
  • antidepressants e.g. fluoxetine, paroxetine
  • 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 or symptoms of allergies
  • 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
  • antifungals e.g. ketoconazole
  • antibiotics e.g. clarithromycin, rifampin
  • medicine to treat HIV infection and AIDS e.g. ritonavir
  • alcohol
  • St John's wort (a herbal preparation)
  • grapefruit and grapefruit juice.
  • medicines to treat epilepsy, pain, and anxiety e.g. gabapentin and pregabalin.

These medicines, dietary supplements or alcohol may be affected by OxyContin tablets, may affect how well OxyContin tablets work or may increase side effects. You may need to use different amounts of your medicines, or take different medicines.

Your doctor or pharmacist has more information on medicines and dietary supplements to be careful with or avoid while taking this medicine.

How to take OxyContin tablets

How much to take

Your doctor will tell you exactly how much to take.

Follow the instructions given to you by your doctor and pharmacist exactly.

How to take it

Swallow OxyContin tablets whole with a full glass of water or other fluid.

OxyContin tablets should be taken one tablet at a time with enough water to ensure complete swallowing immediately after placing it in the mouth.

Do not pre-soak, lick or wet the tablet before placing in your mouth.

Do not break, cut, chew, crush or dissolve the tablets. OxyContin tablets are only designed to work properly if swallowed whole. The tablets may release all their contents at once if broken, cut, chewed, crushed or dissolved which can be dangerous and cause serious problems, such as an overdose, which may be fatal.

If you have trouble swallowing your tablets whole, talk to your doctor.

You must only take OxyContin tablets by mouth. Taking this medicine in a manner other than that prescribed by your doctor can be harmful to your health.

There are no data on rectal administration of OxyContin tablets, therefore rectal administration of OxyContin tablets is not recommended.

When to take it

Take OxyContin tablets every 12 hours.

Take OxyContin tablets regularly to control the pain. Taking them at the same time each day will assist in ensuring the best effect in improving your pain. If however, you begin to experience worsening pain and you are taking your OxyContin tablets as prescribed, contact your doctor as your dosage may have to be reviewed.

How long to take it

Continue taking your medicine for as long as your doctor tells you.

If you stop taking this medicine suddenly, your 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 forget to take it

If you forget to take your tablets, contact your doctor or pharmacist for advice.

Do not take a double dose to make up for the dose you have missed. This will increase the chance of you getting unwanted side effects.

If you have trouble remembering when to take your medicine, ask your pharmacist for hints. For example, take your medicine at the same time each morning and evening such as 8 a.m. and 8 p.m.

If you take too much (overdose)

If you or someone else receive 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 steps even if someone other than you have accidentally used OxyContin 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 taken too much OxyContin, you should immediately telephone your doctor or the Poisons Information Centre (Australia: telephone 13 11 26) , or go to Emergency Department at your nearest hospital.

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

While you are taking it

Things you must do

Take OxyContin tablets exactly as your doctor has prescribed.

Before you start on a new medicine, remind your doctor and pharmacist that you are taking OxyContin tablets.

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

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.

If you become pregnant while taking 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. Also tell your doctor if you are having any problems or difficulties while you are being treated with OxyContin tablets.

Tolerance to oxycodone may develop which means that the effect of the medicine may decrease. If this happens, your doctor may review your dose so that you get adequate pain relief.

Keep enough OxyContin tablets with you to last over weekends and holidays.

Things you must not do

Do not drink alcohol while you are taking OxyContin tablets. Drinking alcohol whilst taking OxyContin tablets 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 take OxyContin tablets to treat any other complaint unless your doctor tells you to.

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

Do not stop taking your medicine, exceed the dose recommended or change the dosage without checking with your doctor. Over time your body may become used to oxycodone. If you stop taking it suddenly, your pain may worsen and you may experience unwanted side effects such as withdrawal symptoms. This is called physical dependence.

If you need to stop taking this medicine, your doctor will gradually reduce the amount you take each day, if possible, before stopping the medicine completely.

Things to be careful of

Do not drive or operate machinery until you know how OxyContin tablets affect you. OxyContin tablets 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 taking OxyContin tablets. If you vomit after your dose, your pain may come back, as you may not have absorbed your medicine. If this happens, speak to your doctor. Your doctor may prescribe some medicine to help you stop vomiting.

Tell your doctor if taking OxyContin tablets causes constipation. Your doctor can advise about your diet, the proper use of laxatives or alternative treatments, and suitable exercise you can do to help manage this.

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 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 take 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 or pharmacist as soon as possible if you do not feel well while you are taking OxyContin tablets. 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 problems such as diarrhoea, feeling sick (nausea), decreased appetite or constipation
  • dry mouth, hiccups, sore throat, or changes in voice
  • excessive sweating
  • feeling anxious or nervous, trouble sleeping or abnormal dreams
  • trouble with your balance
  • new problems with your eyesight
  • skin rash, itching, chills or fever
  • muscle problems such as spasms, twitching or tremors
  • swelling of legs or ankles
  • absence of menstrual periods
  • impotence
  • 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
  • choking, gagging, regurgitation, tablets stuck in throat or trouble swallowing the tablets
  • abnormal thinking, changes in mood or feeling deep sadness
  • drowsiness, feeling faint or fainting, or dizziness especially when standing up
  • slow or noticeable heartbeats
  • headache or confusion
  • unusual weakness, loss of strength or trouble walking
  • 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.

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 your 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 hospitalisation.

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

After taking it

Storage

Keep your tablets in the blister pack until it is time to take them. If you take the tablets out of the blister pack they may not keep as well.

Keep your tablets in a cool, dry place, where the temperature stays below 25°C.

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 on hot days. 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 you no longer need to use 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.

Product description

What it looks like

The reformulated OxyContin® tablets are round, film-coated tablets. They are available in six strengths which are as follows:

10 mg - white, marked "ON" on one side and 10 on the other

15 mg - grey, marked "ON" on one side and 15 on the other

20 mg - pink, marked "ON" on one side and 20 on the other

30 mg - brown, marked "ON" on one side and 30 on the other

40 mg - yellow, marked "ON" on one side and 40 on the other

80 mg - green, marked "ON" on one side and 80 on the other.

OxyContin® tablets come in boxes containing blister packs of 28 tablets.

Ingredients

Active ingredients:

  • 10 mg tablets contain 10 mg oxycodone hydrochloride
  • 15 mg tablets contain 15 mg oxycodone hydrochloride
  • 20 mg tablets contain 20 mg oxycodone hydrochloride
  • 30 mg tablets contain 30 mg oxycodone hydrochloride
  • 40 mg tablets contain 40 mg oxycodone hydrochloride
  • 80 mg tablets contain 80 mg oxycodone hydrochloride.

Inactive ingredients (reformulated tablets):

  • polyethylene oxide
  • butylated hydroxytoluene (BHT)
  • magnesium stearate.

In addition, the reformulated tablets also contain the ingredients listed below:

  • 10 mg - Opadry White
  • 15 mg - Opadry complete film coating system Grey
  • 20 mg - Opadry Pink
  • 30 mg - Opadry Brown
  • 40 mg - Opadry Yellow
  • 80 mg - Opadry Green.

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

Sponsor

OxyContin® tablets are supplied in Australia by:

Mundipharma Pty Limited
ABN 87 081 322 509
10 Carrington Street
Sydney, NSW, 2000
Phone: 1800 188 009

® OXYCONTIN is a trade mark of MUNDIPHARMA.

This leaflet was updated in July 2023

Please check with your pharmacist that this is the latest version of the leaflet available.

Australian Registration Numbers for OxyContin® tablets:

10 mg: AUST R 200031

15 mg: AUST R 200026

20 mg: AUST R 200033

30 mg: AUST R 200025

40 mg: AUST R 200024

80 mg: AUST R 200030

OXYCONTIN-CMIv1- CCDSv18, 19 & 20

Published by MIMS October 2023

BRAND INFORMATION

Brand name

OxyContin

Active ingredient

Oxycodone hydrochloride

Schedule

S8

 

1 Name of Medicine

Oxycodone hydrochloride.

2 Qualitative and Quantitative Composition

OxyContin modified release tablets contain the following quantities of oxycodone hydrochloride:
OxyContin 10 mg contains oxycodone hydrochloride 10 mg;
OxyContin 15 mg contains oxycodone hydrochloride 15 mg;
OxyContin 20 mg contains oxycodone hydrochloride 20 mg;
OxyContin 30 mg contains oxycodone hydrochloride 30 mg;
OxyContin 40 mg contains oxycodone hydrochloride 40 mg;
OxyContin 60 mg contains oxycodone hydrochloride 60 mg;
OxyContin 80 mg contains oxycodone hydrochloride 80 mg.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Modified release tablets:
10 mg: round, unscored, white-coloured, bi-convex tablets, debossed with ON (underscored) on one side and 10 on the other.
15 mg: round, unscored, grey-coloured, bi-convex tablets, debossed with ON (underscored) on one side and 15 on the other.
20 mg: round, unscored, pink-coloured, bi-convex tablets, debossed with ON (underscored) on one side and 20 on the other.
30 mg: round, unscored, brown-coloured, bi-convex tablets, debossed with ON (underscored) on one side and 30 on the other.
40 mg: round, unscored, yellow-coloured, bi-convex tablets, debossed with ON (underscored) on one side and 40 on the other.
60 mg: round, unscored, red-coloured, bi-convex tablets, debossed with ON (underscored) on one side and 60 on the other.
80 mg: round, unscored, green-coloured, bi-convex tablets, debossed with ON (underscored) on one side and 80 on the other.
OxyContin tablets are modified release tablets designed to provide delivery of oxycodone over 12 hours.
OxyContin 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg* and 80 mg tablets comprise a matrix formulation with a hydrogelling property (i.e. particles or whole tablets become highly viscous (gel-like) in water), intended to be crush-deterrent and to reduce the rapid release of oxycodone upon accidental or intentional misuse. The tablets have been heat-treated to increase the mechanical strength of the tablet.
The physical properties of the reformulated OxyContin tablets were examined following an extensive battery of physical manipulations. Beyond demonstrating that the reformulated OxyContin tablets are harder to crush than another controlled release oxycodone formulation, testing over the range of the reformulated OxyContin tablets fragment sizes showed that some of the controlled release properties were still retained. Hydrogelling properties continued to be demonstrated.
*OxyContin 60 mg tablets are not marketed in Australia.

4 Clinical Particulars

4.1 Therapeutic Indications

OxyContin modified release tablet is indicated for the management of severe pain where:
other treatment options have failed, are contraindicated, not tolerated or are otherwise inappropriate to provide sufficient management of pain, and
the pain is opioid-responsive; and
requires daily, continuous, long term treatment.
OxyContin modified release tablet is not indicated for use in chronic non-cancer pain other than in exceptional circumstances.
OxyContin modified release tablet is not indicated as an as-needed (PRN) analgesia.

4.2 Dose and Method of Administration

OxyContin tablets 60 mg* and 80 mg should only be used in opioid-tolerant patients. These tablet strengths may cause fatal respiratory depression in patients not previously exposed to opioids (opioid naïve).
OxyContin tablets are to be swallowed whole, and are not to be cut, broken, chewed, crushed or dissolved. The tablets have been hardened to reduce the risk of being accidently or intentionally broken, chewed or crushed. Taking cut, broken, chewed, crushed or dissolved OxyContin tablets could lead to the rapid release and absorption of a potentially fatal dose of oxycodone.
To avoid difficulty swallowing, OxyContin tablets should not be pre-soaked, licked or otherwise wetted prior to placing in the mouth and should be taken one tablet at a time with enough water to ensure complete swallowing immediately after placing it in the mouth.
There are no data on rectal administration of OxyContin tablets, therefore rectal administration of OxyContin tablets is not recommended.
Do not administer OxyContin tablets via nasogastric, gastric or other feeding tubes as it may cause obstruction of feeding tubes.
It is recommended that patients take the medication in a consistent manner in relation to the timing of meals.
Alcoholic beverages should be avoided by patients while being treated with OxyContin tablets.

Treatment goals and discontinuation.

Before initiating treatment with oxycodone, a treatment strategy including treatment duration and treatment goals, and a plan for end of the treatment, should be agreed together with the patient, in accordance with pain management guidelines. During treatment, there should be frequent contact between the physician and the patient to evaluate the need for continued treatment, consider discontinuation and to adjust dosages if needed. When a patient no longer requires therapy with oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal. In absence of adequate pain control, the possibility of hyperalgesia, tolerance and progression of underlying disease should be considered (see Section 4.4 Special Warnings and Precautions for Use).
*OxyContin 60 mg tablets are not marketed in Australia.

Adults, elderly and children over 12 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. OxyContin tablets should be taken at 12-hourly intervals. Appropriate pain management principles of careful assessment and ongoing monitoring should be followed at regular intervals, including reassessing the need for continued opioid therapy. The dosage is dependent on the severity of the pain, and the patient's previous history of analgesic requirements.
The usual starting dose for opioid-naïve patients or patients presenting with severe pain uncontrolled by weaker opioids (especially if they are receiving concurrent sedatives, muscle relaxants or other CNS medicines) is 10 mg 12-hourly.
The dose should then be carefully titrated with longitudinal patient monitoring, assessing whether the pain is opioid responsive and providing the patient significant pain relief.
Increasing severity of pain may require an increased dosage of OxyContin tablets to achieve a stable dose that provides acceptable pain relief. The correct dosage for any individual patient is that which controls the pain and is well-tolerated, for a full 12 hours. If higher doses are necessary, increases should be made, where possible, in 25%-50% increments.
Patients who experience breakthrough pain may require dosage adjustment or rescue medication. The need for rescue medication more than twice a day indicates that the patient should be reassessed and, only if appropriate, the dosage of OxyContin tablets should be increased. There are no well-controlled clinical studies evaluating the safety and efficacy with dosing more frequently than every 12 hours.
Patients receiving oral morphine before OxyContin tablet therapy should have their daily dose based on the following ratio: 10 mg of oral oxycodone is equivalent to 20 mg of oral morphine. It is emphasised that this is a guide to the dose of OxyContin tablets required only. Inter-patient variability requires that each patient is carefully titrated to the appropriate dose.
Controlled pharmacokinetic studies in elderly patients (aged over 65 years) have shown that compared with younger adults the clearance of oxycodone is only slightly reduced. No untoward adverse drug reactions were seen based on age, therefore adult doses and dosage intervals are appropriate.

Children under 12 years.

OxyContin tablets are not recommended for children under 12 years of age.

Patients with renal or hepatic impairment.

The dose initiation should follow a conservative approach in these patients. The recommended adult starting dose should be reduced by 1/3 to 1/2, and each patient should be titrated to adequate pain control according to their clinical situation (see Section 4.4 Special Warnings and Precautions for Use).

Patients transferring from other opioid formulations.

Patients receiving other oral oxycodone formulations may be transferred to OxyContin tablets at the same total daily dosage, equally divided into two 12-hourly OxyContin tablet doses. For patients who are receiving an alternative opioid, the "oral oxycodone equivalent" of the analgesic presently being used should be determined. Having determined the total daily dosage of the present analgesic, Table 1 can be used to calculate the approximate daily oral oxycodone dosage that should provide equivalent analgesia. The total daily oral oxycodone dosage should then be equally divided into two 12-hourly OxyContin tablet doses.

4.3 Contraindications

Hypersensitivity to opioids or to any of the constituents of OxyContin tablets, acute respiratory disease, severe respiratory disease, respiratory depression, cor pulmonale, cardiac arrhythmias, acute asthma or other obstructive airways disease, suspected mechanical gastrointestinal obstruction (e.g. bowel obstruction, strictures) or any diseases/conditions that affect bowel transit (e.g. ileus of any type), suspected surgical abdomen, severe renal impairment (creatinine clearance < 10 mL/min), severe hepatic impairment (see Section 4.4 Special Warnings and Precautions for Use), delayed gastric emptying, acute alcoholism, 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 two weeks of discontinuation of their use. Not recommended for pre-operative use or for the first 24 hours post-operatively.
Pregnancy.

4.4 Special Warnings and Precautions for Use

Hazardous and harmful use.

OxyContin contains the opioid oxycodone hydrochloride and is a potential drug of abuse, misuse and addiction. Addiction can occur in patients appropriately prescribed OxyContin at recommended doses.
The risk of addiction is increased in patients with a personal or family history of substance abuse (including alcohol and prescription and illicit drugs) or mental illness. 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 OxyContin.
All patients receiving opioids should be routinely monitored for signs of 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 of oral or transdermal forms of opioids by parenteral administration can result in serious adverse events, which may be fatal.
Tolerance and physical and/or psychological dependence may develop upon repeated administration of opioids such as oxycodone. Repeated use of oxycodone can lead to Opioid Use Disorder (OUD). A higher dose and longer duration of opioid treatment can increase the risk of developing OUD. Abuse or intentional misuse of oxycodone 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 use disorders (including alcohol use disorder), in current tobacco users or in patients with a personal history of other mental health disorders (e.g. major depression, anxiety and personality disorders).
Before initiating treatment with oxycodone and during the treatment, treatment goals and a discontinuation plan should be agreed with the patient (see Section 4.2 Dose and Method of Administration). Before and during treatment the patient should also be informed about the risks and signs of OUD. If these signs occur, patients should be advised to contact their physician.
Patients will require monitoring for signs of drug-seeking behaviour (e.g. too early requests for refills). This includes the review of concomitant opioids and psycho-active drugs (like benzodiazepines). For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered.
Patients should be advised not to share OxyContin with anyone else.

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 OxyContin 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, in patients with renal and hepatic impairment and in patients with existing 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).
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 can 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 fashion. In patients who present with CSA, consider decreasing the total opioid dosage. Opioids may also cause worsening of pre-existing sleep apnoea (see Section 4.8 Adverse Effects (Undesirable Effects)).

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 OxyContin modified release tablets with CNS depressant medicines, such as other opioid analgesics, benzodiazepines, gabapentinoids, cannabis, sedatives, hypnotics, tricyclic antidepressants, antipsychotics, antihistamines, centrally-active anti-emetics and other CNS depressants, should be reserved for patients for whom other treatment options are not possible. If a decision is made to prescribe OxyContin modified release tablets 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 taking OxyContin modified release tablets.

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 Section 4.4 Special Warnings and Precautions for Use, Hazardous and harmful use). 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 Section 4.4 Special Warnings and Precautions for Use, Ceasing opioids).

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.
When discontinuing OxyContin modified release tablets in a person who may be physically-dependent, the drug should not be ceased abruptly but withdrawn by tapering the dose gradually (see Section 4.4 Special Warnings and Precautions for Use, Ceasing opioids).
One doctor only should be responsible for the prescription and monitoring of the patient's opioid use.

Accidental ingestion/exposure.

Accidental ingestion or exposure of OxyContin modified release tablets, especially by children, can result in a fatal overdose of OxyContin modified release tablets. Patients and their caregivers should be given information on safe storage and disposal of unused OxyContin (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 Section 4.4 Special Warnings and Precautions for Use, 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 Section 4.4 Special Warnings and Precautions for Use, 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. 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.

Drug abuse studies.

Intranasal abuse.

In a human abuse liability study, milled OxyContin 30 mg tablets produced subjective responses on each of the four established primary measures that were greater than placebo but significantly less than the responses for another, conventional finely crushed controlled release oxycodone tablets formulation 30 mg, or a fine powder of oxycodone 30 mg when administered intranasally in healthy recreational opioid users with a history of intranasal drug abuse/misuse (n = 27). The primary measures were: 'drug liking at this moment'; 'overall drug liking'; 'subjective drug value'; 'Addiction Research Centre Inventory (ARCI) Morphine Benzedrine Group (MBG)' scales.
Objective measures of pupil diameter and other subjective measures were consistent with a lower opioid effect. Measurements of intranasal irritation showed increased irritation, particularly related to nasal stuffiness, with OxyContin tablets compared with another conventional controlled release oxycodone tablets formulation or oxycodone powder.
In a tolerability and safety study with healthy subjects under fasting conditions, milled OxyContin tablets were shown to cause increased nasal discomfort, particularly related to increased nasal stuffiness, and a decrease in runny nose scores when compared with another finely milled controlled release oxycodone tablets formulation, when administered intranasally. Although total AUC was similar for all treatments, Cmax was 67% for coarsely and 77.6% for finely milled OxyContin tablets (ratio of metric means expressed as a percent, transformed back to the linear scale) compared with the other finely milled conventional controlled release oxycodone tablets formulation and Tmax was later with OxyContin tablets.
An additional study was conducted to assess the administration site safety and tolerability of intranasally administered milled OxyContin tablets placebo vs another crushed conventional controlled release oxycodone tablets formulation placebo. Endoscopy photographs showed residual particles in the nasal cavity at 30 minutes following administration of OxyContin tablets placebo.

Accidental or intentional oral misuse.

A study in healthy subjects was conducted to characterize the impact of chewing intact and tampered tablets and subsequent swallowing, on the pharmacokinetics of OxyContin tablets under fasting conditions. The manufacturing process for OxyContin tablets imparts increased hardness to the tablets. Subjects were required to complete a chewing qualification assessment prior to receiving their initial study doses.
The results showed that under both normal and vigorous chewing conditions, OxyContin tablets retained some of their controlled release characteristics. Peak plasma levels of oxycodone (Cmax) for OxyContin tablets were 13.5% lower when swallowed after vigorous chewing and 23.6% lower when swallowed after normal chewing (ratio of metric means expressed as a percent, transformed back to the linear scale) when compared with another chewed conventional formulation of controlled release oxycodone tablets. The time to reach peak plasma levels (Tmax) was also delayed for OxyContin tablets compared with the other conventional controlled release oxycodone tablet formulation, under both vigorous (1.5 vs 1.0 hours respectively) and normal (2.38 vs 1.13 hours respectively) chewing conditions.

Formulation.

OxyContin tablets are intended for oral use only. The modified release tablets must be swallowed whole, and not broken, chewed or crushed. The administration of broken, chewed or crushed modified release oxycodone tablets leads to a rapid release and absorption of a potentially fatal dose of oxycodone. Parenteral venous injection of the tablet constituents can be expected to result in local tissue necrosis, pulmonary granulomas and serious adverse reactions which may be fatal.

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.

Use in hepatic impairment.

In hepatic impairment, the administration of OxyContin tablets 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 hepatic function. Therefore, initiation of dosing in patients with hepatic impairment should be reduced to 1/3 to 1/2 of the usual dose with cautious titration.

Use in renal impairment.

In renal impairment, the administration of OxyContin tablets 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 function. Therefore, initiation of dosing in patients with renal impairment (CrCl < 60 mL/min) should be reduced to 1/3 to 1/2 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.
As with other opioid initiation and titration, doses in elderly patients who are debilitated should be reduced to 1/3 to 1/2 of the usual doses.

Paediatric use.

OxyContin tablets are not recommended for use in children under 12 years of age (see Section 4.2 Dose and Method of Administration).

Effects on laboratory tests.

No data available.

Special risk patients.

As with all opioids, a reduction in dosage may be advisable in hypothyroidism. Use with caution in patients with hypotension, hypovolaemia, diseases of the biliary tract, pancreatitis, inflammatory bowel disorders, prostatic hypertrophy, adrenocortical insufficiency (Addison's disease), toxic psychosis, sleep apnoea, constipation, myxoedema. As with all opioid preparations, patients who are to undergo cordotomy or other pain-relieving surgical procedures should not receive OxyContin tablets for 24 hours before surgery. Pain in the immediate pre-operative period, and any symptoms of opioid withdrawal, should be managed with short-acting analgesic agents. If further treatment with OxyContin tablets is then indicated the dosage should be adjusted to the new post-operative requirement.
As with all opioid preparations, OxyContin tablets 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, OxyContin tablets should be discontinued immediately.
Use caution when prescribing OxyContin tablets for patients who have any underlying GI disorders that may predispose them to intestinal obstruction. Patients with underlying GI disorders such as oesophageal cancer or colon cancer with a small gastrointestinal lumen are at greater risk.
OxyContin tablets should not be taken by patients with difficulty in swallowing or who have been diagnosed with narrowing of the oesophagus. If patients experience swallowing difficulties (e.g. choking, gagging, discomfort, regurgitation, tablets stuck in the throat) after taking OxyContin tablets, they should be advised to seek immediate medical attention.

Endocrine effects.

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.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Anticholinergic agents.

Concurrent use with oxycodone with anticholinergics or medications with anticholinergics activity (e.g. tricyclic antidepressants, antihistamines, antipsychotics, muscle relaxants, antiparkinson 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 increased risk of orthostatic hypotension.

CNS depressants.

Concurrent use of oxycodone with CNS depressants (include, but are not limited to: sedatives (including benzodiazepines, antipsychotics, antidepressants, anxiolytics, centrally-active anti-emetics, cannabis, hypnotics, general anaesthetics, phenothiazines, other tranquillisers, alcohol, other opioids, gabapentinoids such as pregabalin and neuroleptic drugs, etc.) increases the risk of profound sedation, respiratory depression, hypotension, death or coma because of additive CNS depressant effects (see Section 4.4 Special Warnings and Precautions for Use, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol).
Intake of alcoholic beverages while being treated with OxyContin tablets 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.

CYP2D6 and CYP3A4 inhibitors and inducers.

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 oxycodone 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 and antidepressants), although such blockade has not yet been shown to be of clinical significance with OxyContin tablets.
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 overexpression 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.

Selective serotonin re-uptake inhibitor (SSRI) or a serotonin norepinephrine re-uptake inhibitor (SNRI).

Concurrent administration of oxycodone with serotonin agents, such as a selective serotonin re-uptake inhibitor (SSRI) or a serotonin norepinephrine re-uptake inhibitor (SNRI) may cause serotonin toxicity. The symptoms of serotonin toxicity may include mental-status changes (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g. hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhea). Oxycodone should be used with caution and the dosage may need to be reduced in patients using these medications.

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 oral 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 Pregnancy Category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing 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 embryofetal 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 pre-natal 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 neonatal opioid withdrawal. 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. OxyContin tablets 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.

4.7 Effects on Ability to Drive and Use Machines

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

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.

Cardiac disorders.

Uncommon: bradycardia, chest pain, palpitations (as part of withdrawal syndrome), ST depression, supraventricular tachycardia.

Ear and labyrinth disorders.

Uncommon: tinnitus, vertigo.

Eye disorders.

Uncommon: miosis, visual impairment.

Gastrointestinal disorders.

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

General disorders and administration site conditions.

Common: asthenia, fatigue, chills, fever.
Uncommon: accidental injury, facial flushing, lymphadenopathy, malaise, muscular rigidity, neck pain, oedema, peripheral oedema, pain, thirst.
Not known: drug withdrawal syndrome neonatal, opioid tolerance*, opioid withdrawal syndrome*.

Hepatobiliary disorders.

Uncommon: biliary spasm, cholestasis, hepatic enzyme increased.

Immune system disorders.

Uncommon: allergic reaction, anaphylactic reaction, anaphylactoid reaction, hypersensitivity.

Injury, poisoning and procedural complications.

Uncommon: medication struck in throat.

Metabolism and nutrition disorders.

Common: decreased appetite.
Uncommon: increased appetite, dehydration, hyponatraemia.

Nervous system disorders.

Very common: dizziness, headache, somnolence.
Common: faintness, sedation, twitching, tremor, lethargy.
Uncommon: amnesia, drowsiness, abnormal gait, convulsion, dysgeusia (taste perversion), hyperkinesia, hypertonia, hypoaesthesia, hypothermia, raised intracranial pressure, muscle contractions involuntary, paraesthesia, seizures, speech disorder, stupor, syncope.
Not known: hyperalgesia.

Psychiatric disorders.

Common: abnormal dreams, anxiety, confusional state, insomnia, nervousness, thinking abnormal, depression.
Uncommon: affect lability, agitation, disorientation, dysphoria, euphoric mood, hallucination, libido decreased, mood altered, restlessness.
Not known: aggression, drug dependence* (see Section 4.4 Special Warnings and Precautions for Use).

Renal and urinary disorders.

Uncommon: ureteric spasm, urinary abnormalities, urinary retention, urinary tract infection.

Reproductive system and breast disorders.

Uncommon: amenorrhoea, erectile dysfunction, hypogonadism.

Respiratory, thoracic and mediastinal disorders.

Common: bronchospasm, dyspnoea, pharyngitis, voice alteration.
Uncommon: respiratory depression, choking.
Not known: central sleep apnoea syndrome.

Skin and subcutaneous tissue disorders.

Very common: pruritus.
Common: hyperhidrosis, rash.
Uncommon: dry skin, exfoliative dermatitis, urticaria and other skin rashes.

Vascular disorders.

Common: orthostatic hypotension.
Uncommon: hypotension, migraine, vasodilatation.

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).
If nausea and vomiting are troublesome, oxycodone may be combined with an antiemetic. Constipation must be treated with appropriate laxatives. Overdose may produce respiratory depression. Compared with other opioids, oxycodone is associated with low histamine release although urticaria and pruritus may occur.
*The frequency of drug dependence, opioid tolerance and opioid withdrawal syndrome cannot be estimated from available evidence (e.g. clinical trials, spontaneous reporting, and the medical literature) and therefore is classified as "not known". 'Not known' should not be interpreted as an indication of the rarity of the occurrence of drug dependence, opioid tolerance and opioid withdrawal syndrome, but a reflection of the limitations in the available evidence that do not support a precise estimate of frequency.

Drug dependence.

The frequency in the above table regarding drug dependence reflects the current evidence, including cumulative data from clinical trials and additional post marketing sources, and indicates that the risk of drug dependence with opioids is highly variable depending upon: definition of drug dependence; duration of treatment; dose; individual patient risk factors; and clinical settings. 'Not known' should not be interpreted as an indication of the rarity of the occurrence of drug dependence, but a reflection of the limitations in the available evidence that do not support a precise estimate of frequency.
Repeated use of oxycodone may lead to drug dependence, even at therapeutic doses. The risk of drug dependence may vary depending on a patient's individual risk factors, dosage, and duration of opioid treatment (see Section 4.4 Special Warnings and Precautions for Use).
As an opioid, oxycodone exposes users to the risks of dependence (both physical and psychological), addiction, abuse, and misuse, as well as opioid use disorder and problematic opioid use. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed oxycodone. Addiction can occur at recommended doses, and if the drug is misused or abused. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g. major depression). The frequency of drug dependence also increases with longer term use or higher doses of oxycodone. (See Section 4.4 Special Warnings and Precautions for Use.)

Opioid tolerance and opioid withdrawal syndrome.

The frequency of in the above table regarding opioid tolerance and opioid withdrawal syndrome reflects the high variability of risk depending upon: definition of tolerance and withdrawal syndrome; dose and duration of treatment; and assessment and monitoring methods (specific to withdrawal syndrome). 'Not known' should not be interpreted as an indication of the rarity of the occurrence of opioid tolerance and opioid withdrawal syndrome, but a reflection of the limitations in the available evidence that do not support a precise estimate of frequency. As an opioid, oxycodone exposes users to the risks of dependence (both physical and psychological), tolerance and withdrawal syndrome (See Section 4.4 Special Warnings and Precautions for Use.)

Post-marketing.

There have been rare post-marketing cases of intestinal obstruction, and exacerbation of diverticulitis, some of which have required medical intervention to remove the tablet.
There have been uncommon post-marketing reports of difficulty swallowing OxyContin 10 mg to 80 mg tablets, potentially due to the swelling and hydrogelling property of the tablets: choking, gagging, regurgitation, tablets stuck in the throat and difficulty swallowing the tablet.

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 www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

Acute overdosage with oxycodone can be manifested by respiratory depression (reduced respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, hypotonia, cold and/or clammy skin, miosis (dilated if hypoxia is severe), and sometimes bradycardia, hypotension, and death. Severe overdose may result in apnoea, pulmonary oedema, circulatory collapse and death. Toxic leukoencephalopathy has been observed with oxycodone overdose. The features of overdose may be delayed with a sustained release product such as OxyContin tablets.

Treatment of oxycodone overdosage.

Primary attention should be given to immediate supportive therapy with the establishment of adequate respiratory exchange through the provision of a patent airway and institution of assisted or controlled ventilation. Adequate body temperature and fluid balance should be maintained. Oxygen, intravenous fluids, vasopressors and other supportive measures should be used as indicated, to manage the circulatory shock accompanying an overdose. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation.
Activated charcoal may reduce absorption of the drug if given within one to two hours after ingestion. Administration of activated charcoal should be restricted to patients who are fully conscious with an intact gag reflex or protected airway. A saline cathartic or sorbitol added to the first dose of activated charcoal may speed gastrointestinal passage of the product. In patients who are not fully conscious or have an impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected.
Whole bowel irrigation (e.g. 1 or 2 litres of polyethylene glycol solution orally per hour until rectal effluent is clear) may be useful for gut decontamination. Whole bowel irrigation is contraindicated in patients with bowel obstruction, perforation, ileus, haemodynamic instability or compromised, unprotected airways and should be used cautiously in debilitated patients and where the condition may be further compromised. Concurrent administration of activated charcoal and whole bowel irrigation may decrease the effectiveness of the charcoal (there may be competition for the charcoal binding site between the polyethylene glycol and the ingested drugs) but the clinical relevance is uncertain. Prolonged periods of observation (days) may be required for patients who have overdosed with long-acting oxycodone preparations.
If there are signs of clinically significant respiratory or cardiovascular depression, the use of an opioid antagonist should be considered. The opioid antagonist naloxone hydrochloride is a specific antidote for respiratory depression due to overdosage or as a result of unusual sensitivity to opioid. The usual intravenous adult dose of naloxone is 0.4 mg or higher (please refer to naloxone product information for further information). The onset of naloxone effect may be delayed by 30 minutes or more. Concomitant efforts at respiratory resuscitation should be carried out. Since the duration of action of oxycodone, particularly sustained release formulations, may exceed that of the antagonist, the patient should be under continued surveillance and doses of the antagonist should be repeated as needed, or an antagonist infusion established, to maintain adequate respiration.
In an individual physically dependent on, or tolerant to, opioids, the administration of the usual dose of opioid antagonist can precipitate an acute withdrawal syndrome. This may lead to agitation, hypertension, tachycardia and risk of vomiting with possible aspiration. The severity of this syndrome will depend on the degree of physical dependence and the dose of antagonist administered. The use of opioid antagonists in such individuals should be avoided if possible. If an opioid antagonist must be used to treat serious respiratory depression in the physically dependent patient, the antagonist should be administered with extreme care by using dosage titration, commencing with 10 to 20% of the usual recommended initial dose.

Toxicity.

Oxycodone toxicity may result from overdosage but because of the great interindividual variation in sensitivity to opioids it is difficult to determine an exact dose of any opioid that is toxic or lethal. Crushing and taking the contents of a modified release dosage form leads to the release of oxycodone in an immediate fashion; this might result in a fatal overdose. 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.

Oxycodone is a full opioid agonist with no antagonist properties whose principal therapeutic action is analgesia. It has an 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 central nervous system (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 vasodilatation, possibly causing pruritus, flushing, red eyes, sweating and/or orthostatic hypotension).

Clinical trials.

A double-blind, placebo-controlled, fixed-dose, parallel group, two-week study was conducted in 133 patients with persistent, moderate to severe pain, who were judged as having inadequate pain control with their current therapy. In this study, OxyContin 20 mg tablets, but not 10 mg tablets, was statistically significant in pain reduction compared with placebo (text from OxyContin US Prescribing Information dated April 2013).

5.2 Pharmacokinetic Properties

Absorption.

Compared with morphine, which has an absolute bioavailability of approximately 30%, oxycodone has a high absolute bioavailability of up to 87% following oral administration.
The mean apparent half-life of OxyContin tablets is 6.5 hours and steady-state is achieved in about one day.
Release of oxycodone from OxyContin tablets is independent of pH under physiological conditions.
OxyContin tablets have an oral bioavailability comparable with immediate release oral oxycodone, but achieve maximal plasma concentrations at about three-five hours compared with 1-1.5 hours for immediate release oral oxycodone. Peak and trough concentrations of oxycodone from OxyContin tablets 10 mg administered 12-hourly are similar to those achieved from immediate release oxycodone 5 mg administered 6-hourly.
Dose proportionality has been established for the 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg* and 80 mg tablet strengths for both peak plasma concentrations (Cmax) and extent of absorption (AUC).
Following ingestion of a high fat meal, peak plasma concentrations may be increased relative to dosing in the fasting state particularly with the higher doses. To minimise potential variability in peak concentrations if interchangeably administered with or without food, it is important that patients take the medication in a consistent manner in relation to the timing of meals.
OxyContin should either always be taken in a fasted state, or always with or just after food, usually with the same standard size of food each time.

Distribution.

Following absorption, oxycodone is distributed throughout the entire body. Approximately 45% is bound to plasma protein.

Metabolism.

Oxycodone is metabolised in the liver to form noroxycodone, oxymorphone, noroxymorphone, 6α 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.
*OxyContin 60 mg tablets are not marketed in Australia.

Excretion.

Oxycodone has an elimination half-life of between 3 - 5 hours, or approximately 4.5 hours. The plasma concentrations are only minimally affected by age, being 15% greater in the elderly compared with young subjects.
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.

5.3 Preclinical Safety Data

Genotoxicity.

Oxycodone was not genotoxic in bacterial gene mutation assays but was positive in the mouse lymphoma assay. In assays of chromosomal damage, genotoxic effects occurred in the human lymphocyte chromosomal aberration assay in vitro, but not in the in vivo bone marrow micronucleus assay in mice.

Carcinogenicity.

Carcinogenicity was evaluated in a 2-year oral gavage study conducted in Sprague-Dawley rats. Oxycodone did not increase the incidence of tumours in male and female rats at doses up to 6 mg/kg/day (equivalent to 6.8 mg/day in men and 24.6 mg/day in women, based on estimated AUC values). The doses were limited by opioid-related pharmacological effects of oxycodone.

6 Pharmaceutical Particulars

6.1 List of Excipients

The inactive ingredients in OxyContin 10, 15, 20, 30, 40, 60 and 80 mg tablets are: polyethylene oxide and magnesium stearate.
The tablets' film coating also contains:
10 mg - Opadry white Y-5R-18024-A (ARTG PI No: 3585);
15 mg - Opadry complete film coating system 05B97512 gray (ARTG PI No: 12507);
20 mg - Opadry complete film coating system YS-1R-14518-A pink (ARTG PI No: 109767);
30 mg - Opadry complete film coating system YS-1-16518-A brown (ARTG PI No: 12505);
40 mg - Opadry yellow YS-1R-12525-A (ARTG PI No: 3587);
60 mg - Opadry complete film coating system 15B25501 red (ARTG PI No: 12506);
80 mg - Opadry green Y-5R-11167-A (ARTG PI No: 3588).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

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.

6.5 Nature and Contents of Container

OxyContin modified release tablets are presented in PVC/PVDC/Al blister packs.
Not all strengths and pack sizes are available in Australia:
10 mg - 20 and 28 tablets in blister packs;
15 mg - 20 and 28 tablets in blister packs;
20 mg - 20 and 28 tablets in blister packs;
30 mg - 20 and 28 tablets in blister packs;
40 mg - 20 and 28 tablets in blister packs;
60 mg - 20 and 28 tablets in blister packs;
80 mg - 20 and 28 tablets in blister packs.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Oxycodone hydrochloride is a white, crystalline odourless powder readily soluble in water, sparingly soluble in ethanol and nearly insoluble in ether.

Chemical name.

4,5α-epoxy-14-hydroxy-3-methoxy-17- methylmorphinan-6-one hydrochloride.

Molecular formula.

Anhydrous form: C18H21NO4.HCl.
Monohydrate form: C18H21NO4.HCl.H2O.

Molecular weight.

Monohydrate form: 369.84.
Anhydrous form: 351.83.

Chemical structure.

Anhydrous form.

CAS number.

124-90-3.

7 Medicine Schedule (Poisons Standard)

S8.

Summary Table of Changes