Document: leaflet MAH GENERIC_PL 29831-0359 change

• leaflet MAH BRAND_PLPI 18799-2760
• leaflet MAH GENERIC_PL 29831-0359

---

PACKAGE LEAFLET: INFORMATION FOR THE USER Oxycodone Hydrochloride 10mg/ml Solution for Injection or Infusion

(referred to as Oxycodone Injection in this leaflet)

Read all of this leaflet carefully before you start to use this medicine.

-    Keep this leaflet. You may need to read it again while you are receiving your treatment.

-    If you have any further questions, please ask your doctor or pharmacist.

-    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

-    If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1.    What Oxycodone Injection is and what it is used for

2.    Before you use Oxycodone Injection

3.    How to use Oxycodone Injection

4.    Possible side effects

5.    How to store Oxycodone Injection

6.    Further information

1. What Oxycodone Injection is and what it is used for

The name of your medicine is Oxycodone Injection. Oxycodone belongs to a group of medicines known as opioid analgesics, these are strong painkillers (analgesic). Oxycodone Injection is used in the treatment of pain requiring the use of a strong painkiller:

•    moderate to severe pain in patients with cancer

•    pain following an operation.

2. Before you use Oxycodone Injection

You should not use Oxycodone Injection if you:

•    are allergic (hypersensitive) to oxycodone or to any of the other ingredients in Oxycodone Injection (see section 6, Further information)

•    are having difficulty breathing

•    are taking drugs called monoamine oxidase inhibitors (MAOIs) for depression or have taken them in the last 2 weeks

•    are pregnant or breast-feeding

•    have a head injury

•    have a condition where your small bowel ceases to function (paralytic ileus)

•    have an abnormally high level of carbon dioxide circulating in the blood (a condition known as hypercarbia)

•    have moderate to severe liver or kidney disease

•    suffer from a disease of the lung known as chronic obstructive pulmonary disease

•    suffer from heart failure resulting from lung disease (cor pulmonale)

•    suffer from chronic constipation

•    suffer from asthma.

Talk to your doctor before using Oxycodone Injection if you:

•    suffer from any problems with your breathing

•    suffer from an underactive thyroid gland

•    suffer from disease of the gall bladder and bile ducts

•    suffer from inflammation of the bowel

•    suffer from diseases of the adrenal glands

•    suffer from pancreatitis

•    have low blood pressure or low blood volume

•    have toxic psychoses (mental illness as a reaction to drugs, toxins or severe illness)

•    have an enlarged prostate gland

•    have raised intracranial pressure

•    have kidney or liver disease

•    are intoxicated with alcohol

•    are suffering from withdrawal symptoms of alcohol. Special care should be taken with elderly, debilitated, weak patients and patients with a history of drug or alcohol abuse. This medicine can cause dependence, if you have any concerns about whether this medicine is suitable for you speak to your doctor or nurse. Taking other medicines

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. The following medicines can affect or be affected by treatment with Oxycodone Injection:

•    tranquilisers and sleeping tablets

1.    NAME OF THE MEDICINAL PRODUCT

Oxycodone Hydrochloride10 mg/ml Solution for Injection or Infusion.

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains oxycodone hydrochloride 10 mg (equivalent to 9 mg of oxycodone base).

Each 1 ml ampoule contains oxycodone hydrochloride 10 mg (equivalent to 9 mg of oxycodone base).

Each 2 ml contains oxycodone hydrochloride 20 mg (equivalent to 18mg of oxycodone base).

This medicinal product contains less than 1 mmol sodium (23 mg) per <dose>. For full list of excipients, see Section 6.1.

3.    PHARMACEUTICAL FORM

Solution for injection or infusion (injection or infusion).

A Clear, colourless solution practically free of particles.

4.    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the treatment of moderate to severe pain in patients with cancer and post-operative pain. For the treatment of severe pain requiring the use of a strong opioid.

4.2    Posology and method of administration Route of administration:

Subcutaneous injection or infusion.

Intravenous injection or infusion.

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:

The following starting doses are recommended. A gradual increase in dose may be required if analgesia is inadequate or if pain severity increases.

i.v. (Bolus): Dilute to 1 mg/ml in 0.9% saline, 5% dextrose or water for injections. Administer a bolus dose of 1 to 10 mg slowly over one to two minutes.

Doses should not be administered more frequently than every four hours. i.v. (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. i.v. (PCA): Dilute to 1 mg/ml in 0.9% saline, 5% dextrose or water for injections. Bolus doses of 0.03 mg/kg should be administered with a minimum lock-out time of five minutes.

s.c. (Bolus): Use as 10 mg/ml concentration. A starting dose of 5 mg is recommended, repeated at four-hourly intervals as required. s.c. (Infusion): Dilute in 0.9% saline, 5% dextrose or water for injections if required. A starting dose of 7.5 mg/day is recommended in opioid naive patients, titrating gradually according to symptom control. Cancer patients transferring from oral oxycodone may require much higher doses (see below).

Transferring patients between oral and parenteral oxycodone:

The dose should be based on the following ratio: 2 mg of oral oxycodone is equivalent to 1 mg of parenteral oxycodone. It must be emphasised that this is a guide to the dose required. Inter-patient variability requires that each patient is carefully titrated to the appropriate dose.

Elderly:

Elderly patients should be treated with caution. The lowest dose should be administered with careful titration to pain control.

Patients with renal and hepatic impairment:

Patients with mild to moderate renal impairment and/or mild hepatic impairment should be treated with caution. The lowest dose should be given with careful titration to pain control.

Children under 18 years:

There are no data on the use of Oxycodone injection in patients under 18 years of age.

Use in non-malignant pain:

Opioids are not first-line therapy for chronic non-malignant pain, nor are they recommended as the only treatment. Types of chronic pain which have been shown to be alleviated by strong opioids include chronic osteoarthritic pain and intervertebral disc disease. The need for continued treatment in non-malignant pain should be assessed at regular intervals. Cessation of therapy:

When a patient no longer requires therapy with oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

4.3    Contraindications

Oxycodone injection is contraindicated in patients with known hypersensitivity to oxycodone or any of the other constituents, or in any situation where opioids are contraindicated; respiratory depression; head injury; paralytic ileus; acute abdomen; chronic obstructive airways disease; cor pulmonale; chronic bronchial asthma; hypercarbia; moderate to severe hepatic impairment; severe renal impairment (creatinine clearance <10 ml/min); chronic constipation; concurrent administration of monoamine oxidase inhibitors or within 2 weeks of discontinuation of their use; pregnancy; lactation.

4.4    Special warnings and precautions for use

The major risk of opioid excess is respiratory depression. As with all opioids, a reduction in dosage may be advisable in hypothyroidism. Use with caution in patients with raised intracranial pressure, hypotension, hypovolaemia, toxic psychoses, diseases of the biliary tract, inflammatory bowel disorders, prostatic hypertrophy, adrenocortical insufficiency, acute alcoholism, delirium tremens, pancreatitis, chronic renal and hepatic disease or severe pulmonary disease and debilitated, elderly and infirm patients. Oxycodone injection should not be used where there is a possibility of paralytic ileus occurring. Should paralytic ileus be suspected or occur during use, Oxycodone injection should be discontinued immediately. The patient may develop tolerance to oxycodone with chronic use and require progressively higher doses to maintain pain control. The patient may develop physical dependence, in which case an abstinence syndrome may be seen following abrupt cessation.

For appropriate patients who suffer with chronic non-malignant pain, opioids should be used as part of a comprehensive treatment programme involving other medications and treatment modalities. A crucial part of the assessment of a patient with chronic non-malignant pain is the patient’s addiction and substance abuse history. Oxycodone injection should be used with particular care in patients with a history of alcohol and drug abuse.

If opioid treatment is considered appropriate for the patient, then the main aim of treatment is not to minimise the dose of opioid but rather to achieve a dose which provides adequate pain relief with a minimum of side effects. There must be frequent contact between physician and patient so that dosage adjustments can be made. It is strongly

•    anaesthetics

•    anti-depressants

•    phenothiazines (often used to treat severe mental illness)

•    neuroleptic drugs (often used to treat severe mental illnesses such as psychosis and schizophrenia)

•    alcohol

•    other opioid painkillers

•    muscle relaxants

•    monoamine oxidase inhibitors (MAOIs) (used in depression) - wait at least 2 weeks after stopping MOAIs before using this medicine.

Taking Oxycodone Injection with food and drink

As with all medicines that act on the central nervous system, it is advised that you do not drink alcohol while using this medicine.

Pregnancy and breast-feeding You should not use this medicine if you are pregnant or breast feeding. Babies born to women dependent on this medicine may experience withdrawal symptoms as well as breathing difficulties.

Driving and using machinery

Oxycodone Injection may cause drowsiness and reduced alertness, do not drive or operate machinery while using this medicine.

This medicine can affect your ability to drive.

Do not drive whilst taking this medicine until you know how this medicine affects you.

It may be an offence to drive if your ability to drive safely is affected.

There is further information for patients who are intending to drive in Great Britain -go to http://www.gov.uk/drug-driving-law Important information about some of the ingredients in Oxycodone Injection

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially sodium-free’.

3. How to use Oxycodone Injection

Your doctor will determine the dose you require. The usual doses in adults are:

Injected into a vein as a single dose:

•    1-10mg given slowly over 1 to 2 minutes

•    this dose may be repeated after 4 hours if required. Infusion through a drip in a vein:

•    starting dose 2mg/hour recommended.

Patient Controlled Analgesia (a drip which allows the patient to top-up the medicine when required):

•    single doses of 0.03mg per kg body weight should be used with a minimum lock-out time of five minutes. Injected under the skin as a single dose:

•    a starting dose of 5mg is recommended

•    repeat every 4 hours as required Infusion through a drip under the skin:

•    in patients new to these painkillers a starting dose of 7.5mg/day is recommended, gradually increasing to control symptoms

•    cancer patients transferring to an infusion from oral oxycodone may require much higher doses.

Transferring patients from oral Oxycodone to Oxycodone Injection

The dose should be based on the following ratio (please note this is only a guide, the dose should be altered depending on patient’s response to treatment):

•    2mg of oral Oxycodone is equivalent to 1mg of Oxycodone Injection.

--------------------

recommended that the physician defines treatment outcomes in accordance with pain management guidelines. The physician and patient can then agree to discontinue treatment if these objectives are not met. Oxycodone has an abuse liability similar to other strong opioids and should be used with caution in opioid-dependent patients. Oxycodone may be sought and abused by people with latent or manifest addiction disorders. As with other opioids, infants who are born to dependent mothers may exhibit withdrawal symptoms and may have respiratory depression at birth. Oxycodone injection contains approximately 5mg sodium per ml i.e. essentially ‘sodium-free’.

4.5    Interaction with other medicinal products and other forms of interaction

There is an enhanced CNS depressant effect with drugs such as tranquillisers, anaesthetics, hypnotics, anti-depressants, sedatives, phenothiazines, neuroleptic drugs, alcohol, other opioids, muscle relaxants and antihypertensives. Monoamine oxidase inhibitors are known to interact with narcotic analgesics, producing CNS excitation or depression with hypertensive or hypotensive crisis.

Oxycodone is metabolised in part via the CYP2D6 and CYP3A4 pathways. While these pathways may be blocked by a variety of drugs, such blockade has not yet been shown to be of clinical significance with this agent.

4.6    Pregnancy and lactation Pregnancy

The effect of oxycodone in human reproduction has not been adequately studied. No studies on fertility or the post-natal effects of intrauterine exposure have been carried out. However, studies in rats and rabbits with oral doses of oxycodone equivalent to 3 and 47 times an adult dose of 160 mg/day, respectively, did not reveal evidence of harm to the foetus due to oxycodone. Oxycodone injection is not recommended for use in pregnancy nor during labour. Infants born to mothers who have received opioids during pregnancy should be monitored for respiratory depression. Lactation

Oxycodone is secreted in breast milk and may cause harmful effects in the newborn (respiratory depression, somnolence, lethargy). Oxycodone is contraindicated during lactation.

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. Therefore patients should not drive or operate machinery, if affected. This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:

•    The medicine is likely to affect your ability to drive

•    Do not drive until you know how the medicine affects you

•    I t is an offence to drive while under the influence of this medicine

•    However, you would not be committing an offence (called ‘statutory defence’) if:

° The medicine has been prescribed to treat a medical or dental problem and

° You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and ° It was not affecting your ability to drive safely

4.8    Undesirable effects

Adverse drug reactions are typical of full opioid agonists. Tolerance and dependence may occur (see Tolerance and Dependence, below). Constipation may be prevented with an appropriate laxative. If nausea or vomiting are troublesome, oxycodone may be combined with an antiemetic. The adverse drug reactions seen whilst being treated with oxycodone were: Endocrine disorders:

Uncommon (>1/1,000, <1/100): syndrome of inappropriate antidiuretic hormone secretion.

Metabolism and nutrition disorders:

Common (>1/100, <1/10): anorexia

Uncommon (>1/1,000, <1/100): dehydration, weight change, peripheral oedema, oedema, thirst.

Psychiatric disorders (see tolerance and dependence below):

Common (>1/100, <1/10): abnormal dreams, anxiety, confusion, insomnia, nervousness, abnormal thinking.

Uncommon (>1/1,000, <1/100): libido decreased, depression, hallucinations, depersonalisation, euphoria, mood changes, agitation, emotional lability. Nervous system disorders:

Very common (>1/10): somnolence, dizziness.

Common (>1/100, <1/10): faintness, asthenia, headache.

Uncommon (>1/1,000, <1/100): abnormal gait, amnesia, hyperkinesia, hypertonia, hypoaesthesia, hypotonia, speech disorder, stupor, tremor, twitching, vertigo, epileptic seizures, paraesthesia, withdrawal syndrome, malaise, muscle contractions involuntary.

Eye disorders:

Uncommon (>1/1,000, <1/100): lacrimation disorder, miosis, abnormal vision. Ear and labyrinth disorders:

Uncommon (>1/1,000, <1/100): tinnitus.

Cardiac disorders:

Common (>1/100, <1/10): Orthostatic hypotension.

Uncommon (>1/1,000, <1/100): palpitations (in the context of withdrawal syndrome), hypotension, syncope.

Vascular disorders:

Uncommon (>1/1,00, < 1/100): vasodilation.

Respiratory, thoracic and mediastinal disorders:

Common (>1/100, <1/10): dyspnoea, bronchospasm.

Uncommon (>1/1,000, <1/100): rhinitis, epistaxis, hiccup, voice alteration, respiratory depression.

Gastrointestinal disorders:

Very common (>1/10): constipation, nausea, vomiting.

Common (>1/100, <1/10): abdominal pain, anorexia, diarrhoea, dry mouth, dyspepsia,

Uncommon (>1/1,000, <1/100): dysphagia, flatulence, gastritis, mouth ulceration, eructation, ileus, stomatitis, biliary spasm, gastrointestinal disorders, taste perversion.

Skin and subcutaneous tissue disorders:

Very common (>1/10): pruritus.

Common (>1/100, <1/10): rash, sweating.

Uncommon (>1/1,000, <1/100): dry skin, urticaria.

Renal and urinary disorders:

Common (>1/100, <1/10): urinary disorders.

Uncommon (>1/1,000, <1/100): urinary retention, ureteral spasm.

Elderly and patients with kidney and liver disease

The lowest dose needed for symptom control should be used. Not to be used in patients under 18 years of age If you take more Oxycodone Injection than you should This medicine will be given to you by your doctor so it is unlikely you will receive too much. Your doctor has information on how to recognise and treat an overdose.

If you stop using Oxycodone Injection Patients can become tolerant to the effects of oxycodone if used over a long time or if they are already using Oxycodone and may require progressively higher doses in order to maintain pain control.

Prolonged use of this medicine may also lead to dependence and if treatment is stopped abruptly the patient may experience withdrawal symptoms. These symptoms include restlessness, running nose and eyes, yawning, sweating, chills, muscle pain, abdominal pain, diarrhoea and prolonged dilation of the pupils. When a patient no longer requires this medicine it is advised to stop treatment gradually over some time in order to prevent withdrawal symptoms.

4. Possible side effects

• sleepiness	• dizziness
• constipation	• nausea
• vomiting	• itching.
Common (occurs in more than 1 in 100 patients)
• abnormal thinking	• breathlessness
• wheezing	• stomach pains
• loss of appetite	• diarrhoea
• dry mouth	• indigestion
• rash	• sweating
• problems passing water	• fever
• chills	• abnormal dreams
• anxiety	• confusion
• problems sleeping	• faintness
• extreme fatigue	• headache
• nervousness	• low blood pressure on
• anorexia	standing.
Uncommon (occurs in fewer than 1 in 100 patients)
• hormone disturbances	• mouth ulcers
• weight change	• change of taste
• decreased sex-drive	• inflammation of the mouth
• hallucinations	• hives or itchy rash
• memory loss	• impotence
• fits	• chest pain
• euphoria	• anaphylaxis
• twitching	• dehydration
• speech problems	• swelling of the legs
• decreased muscle tone	• depression
• excitedness	• problems walking
• agitation	• mood changes
• general malaise	• vertigo
• constricted pupils	• depersonalisation
• ringing in the ears	• involuntary movements
• low blood pressure	• increased muscle tone
• dilated blood vessels	• drug dependence
• hiccups	• unresponsiveness
• difficulty breathing	• withdrawal
• flatulence	• running eyes
• abnormal vision	• problems swallowing
• abnormal heart rhythm	• inflammation of stomach
• blackouts	• belching
• nosebleeds	• stops menstrual period
• voice alteration	• allergy
• gall bladder problems	• changed or reduced
• dry skin	sensation

Reproductive system and breast disorders:

Uncommon (>1/1,000, <1/100): impotence, amenorrhoea.

General disorders and administration site conditions:

Common (>1/100, <1/10): fever, chills.

Uncommon (>1/1,000, <1/100): chest pain, allergic reaction, anaphylactic reaction, anaphylactoid reaction, drug dependence.

Tolerance and Dependence:

The patient may develop tolerance to the drug with chronic use and require progressively higher doses to maintain pain control. Prolonged use of Oxycodone injection may lead to physical dependence and a withdrawal syndrome may occur upon abrupt cessation of therapy. When a patient no longer requires therapy with oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal. The opioid abstinence or withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia and mydriasis. Other symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhoea, or increased blood pressure, respiratory rate or heart rate.

The development of psychological dependence (addiction) to opioid analgesics in properly managed patients with pain has been reported to be rare. However, data are not available to establish the true incidence of psychological dependence (addiction) in chronic pain patients.

Oxycodone injection should be used with particular care in patients with a history of alcohol and drug abuse.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal roduct is important. It allows continued monitoring of the benefit/risk alance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: United Kingdom Yellow Card Scheme www.mhra.gov.uk/yellowcard Ireland

HPRA Pharmacovigilance Earlsfort Terrace IRL - Dublin 2 Tel: +353 1 6764971 Fax: +353 1 6762517 Website: www.hpra.ie e-mail: medsafety@hpra.ie

Malta

ADR Reporting

www.medicinesauthority.gov.mt/adrportal

4.9 Overdose Symptoms of overdosage

Signs of oxycodone toxicity and overdosage are pin-point pupils, respiratory depression, hypotension and hallucinations. Nausea and vomiting are common in less severe cases. Non-cardiac pulmonary oedema and rhabdomyolysis are particularly common after intravenous injection of opioid analgesics. Circulatory failure and somnolence progressing to stupor or coma, skeletal muscle flaccidity, bradycardia and death may occur in more severe cases.

The effects of overdosage will be potentiated by the simultaneous ingestion of alcohol or other psychotropic drugs.

Treatment of overdosage

Primary attention should be given to the establishment of a patent airway and institution of assisted or controlled ventilation.

In the case of massive overdosage, administer naloxone intravenously (0.4 to 2mg for an adult and 0.01mg/kg body weight for children) if the patient is in a coma or respiratory depression is present. Repeat the dose at 2 minute intervals if there is no response. If repeated doses are required then an infusion of 60% of the initial dose per hour is a useful starting point. A solution of 10 mg made up in 50 ml dextrose will produce 200 micrograms/ml for infusion using an IV pump (dose adjusted to the clinical response). Infusions are not a substitute for frequent review of the patient’s clinical state.

Intramuscular naloxone is an alternative in the event that IV access is not possible. As the duration of action of naloxone is relatively short, the patient must be carefully monitored until spontaneous respiration is reliably re-established. Naloxone is a competitive antagonist and large doses (4 mg) may be required in seriously poisoned patients.

For less severe overdosage, administer naloxone 0.2 mg intravenously followed by increments of 0.1 mg every 2 minutes if required.

The patient should be observed for at least 6 hours after the last dose of naloxone.

Naloxone should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to oxycodone overdosage. Naloxone should be administered cautiously to persons who are known, or suspected, to be physically dependent on oxycodone.

In such cases, an abrupt or complete reversal of opioid effects may precipitate pain and an acute withdrawal syndrome.

5. PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: Natural opium alkaloids ATC code: N02A A05

Oxycodone is a full opioid agonist with no antagonist properties. It has an affinity for kappa, mu and delta opioid receptors in the brain and spinal cord. Oxycodone is similar to morphine in its action. The therapeutic effect is mainly analgesic, anxiolytic, antitussive and sedative.

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

In vitro and animal studies indicate various effects of natural opioids, such as morphine, on components of the immune system; the clinical significance of these findings is unknown. Whether oxycodone, a semisynthetic opioid, has immunological effects similar to morphine is unknown.

5.2    Pharmacokinetic properties

Pharmacokinetic studies in healthy subjects demonstrated an equivalent availability of oxycodone from Oxycodone injection when administered by the intravenous and subcutaneous routes, as a single bolus dose or a continuous infusion over 8 hours.

Following absorption, oxycodone is distributed throughout the entire body. Approximately 45% is bound to plasma protein. It is metabolised in the liver to produce noroxycodone, oxymorphone and various conjugated glucuronides. The analgesic effects of the metabolites are clinically insignificant.

The active drug and its metabolites are excreted in both urine and faeces.

United Kingdom

Yellow Card Scheme

www.mhra.gov.uk/yellowcard

Ireland

HPRA Pharmacovigilance Earlsfort Terrace IRL - Dublin 2 Tel: +353 1 6764971 Fax: +353 1 6762517 Website: www.hpra.ie e-mail:medsafety@hpra.ie Malta

ADR Reporting

www.medicinesauthority.gov.mt/

adrportal

By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Oxycodone Injection

Keep out of the reach and sight of children.

•    This medicinal product does not require any special temperature storage conditions.

•    Keep the ampoules in the outer carton in order to protect from light.

•    Do not use after the expiry date (shown as Exp. on the packaging). The expiry date refers to the last day of the month, your doctor or nurse will check for this.

•    This medicine should be used immediately after opening. Medicines should not be disposed of via wastewater or household waste. These measures will help protect the environment.

6. Further information

What Oxycodone Injection contains

The active ingredient is oxycodone hydrochloride. Each ml contains oxycodone hydrochloride 10mg (equivalent to 9mg oxycodone base).

Each 1 ml ampoule contains oxycodone hydrochloride 10 mg (equivalent to 9 mg of oxycodone base).

Each 2 ml contains oxycodone hydrochloride 20 mg (equivalent to 18mg of oxycodone base).

The other ingredients are: citric acid monohydrate, sodium citrate, sodium chloride, hydrochloric acid, sodium hydroxide and water for injections.

What Oxycodone Injection looks like and the contents of the pack

Oxycodone Injection is a clear colourless solution and is supplied in packs of 5 containing either 1ml or 2ml clear glass ampoules.

Marketing Authorisation Holder: Wockhardt UK Ltd, Ash Road North, Wrexham, LL13 9UF, UK. Manufacturer: CP Pharmaceuticals Ltd, Ash Road North, Wrexham, LL13 9UF, UK.

This medicinal product is authorised in the Member States of the EEA under the following names:

UK: Oxycodone Hydrochloride 10mg/ml

Solution for Injection or Infusion

Ireland: Oxycodone Hydrochloride 10mg/ml

Solution for Injection or Infusion

Cyprus: Oxycodone Hydrochloride 10mg/ml

Solution for Injection or Infusion

Malta: Oxycodone Hydrochloride 10mg/ml

Solution for Injection or Infusion

Poland: Oxycodone Hydrochloride Wockhardt

Other formats:

To listen to or request a copy of this leaflet in Braille, large print or audio please call, free of charge: 0800 198 5000 (UK Only). Please be ready to give the following information:

Product name	Reference number
Oxycodone 10mg/ml Solution for Injection	PL 29831/0359

This is a service provided by the Royal National Institute of Blind People.

For the Republic of Ireland please call UK +44 1978 669272

This leaflet was last revised in 03/2016.

105210/8    fwOCKHARDT

--------------------

The plasma concentrations of oxycodone are only minimally affected by age, being 15% greater in elderly as compared to young subjects.

Female subjects have, on average, plasma oxycodone concentrations up to 25% higher than males on a body weight adjusted basis.

The drug penetrates the placenta and can be found in breast milk.

When compared to normal subjects, patients with mild to severe hepatic dysfunction may have higher plasma concentrations of oxycodone and noroxycodone, and lower plasma concentrations of oxymorphone. There may be an increase in the elimination half-life of oxycodone and this may be accompanied by an increase in drug effects.

When compared to normal subjects, patients with mild to severe renal dysfunction may have higher plasma concentrations of oxycodone and its metabolites. There may be an increase in the elimination half-life of oxycodone and this may be accompanied by an increase in drug effects.

5.3 Preclinical safety data

Oxycodone was not mutagenic in the following assays: Ames Salmonella and E. Coli test with and without metabolic activation at doses of up to 5000 pg, chromosomal aberration test in human lymphocytes (in the absence of metabolic activation and with activation after 48 hours of exposure) at doses of up to 1500 pg/ml, and in the in vivo bone marrow micronucleus assay in mice (at plasma levels of up to 48 pg ml). Mutagenic results occurred in the presence of metabolic activation in the human chromosomal aberration test (at greater than or equal to 1250 pg ml) at 24 but not 48 hours of exposure and in the mouse lymphoma assay at doses of 50 pg/ml or greater with metabolic activation and at 400 pg/ml or greater without metabolic activation. The data from these tests indicate that the genotoxic risk to humans may be considered low.

Studies of oxycodone in animals to evaluate its carcinogenic potential have not been conducted owing to the length of clinical experience with the drug substance.

6.    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Citric acid monohydrate Sodium citrate Sodium chloride

Hydrochloric acid (for pH adjustment)

Sodium hydroxide (for pH adjustment)

Water for injections

6.2    Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

Cyclizine at concentrations of 3 mg/ml or less, when mixed with Oxycodone injection, either undiluted or diluted with water for injections, shows no sign of precipitation over a period of 24 hours storage at room temperature. Precipitation has been shown to occur in mixtures with Oxycodone injection at cyclizine concentrations greater than 3 mg/ml or when diluted with 0.9% saline. It is recommended that water for injections be used as a diluent when cyclizine and oxycodone hydrochloride are co-administered either intravenously or subcutaneously as an infusion. Prochlorperazine is chemically incompatible with Oxycodone injection.

6.3    Shelf life Unopened: 2 years.

The injection should be given immediately after opening the ampoule. Once opened, any unused portion should be discarded. Chemical and physical in-use stability has been demonstrated for 24 hours at room temperature. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution, dilution, etc has taken place in controlled and validated aseptic conditions.

6.4    Special precautions for storage

This medicinal product does not require any special temperature storage conditions.

Keep the ampoules in the outer carton in order to protect from light.

6.5    Nature and contents of container Type I clear glass ampoules: 1 ml and 2 ml.

Pack size: 5 ampoules.

6.6    Special precautions for disposal

Oxycodone injection has been shown to be compatible with the following drugs:

Hyoscine butylbromide Hyoscine hydrobromide Dexamethasone sodium phosphate Haloperidol

Midazolam hydrochloride Metoclopramide hydrochloride Levomepromazine hydrochloride

Oxycodone injection, undiluted or diluted to 1 mg/ml with 0.9% w/v saline, 5% w/v dextrose or water for injections, is physically and chemically stable when in contact with representative brands of polypropylene or polycarbonate syringes, polyethylene or PVC tubing, and PVC or EVA infusion bags, over a 24 hour period at room temperature.

The injection, whether undiluted or diluted to 1 mg/ml in the infusion fluids used in these studies and contained in the various assemblies, does not need to be protected from light.

Inappropriate handling of the undiluted solution after opening of the original ampoule, or of the diluted solutions may compromise the sterility of the product.

7.    MARKETING AUTHORISATION HOLDER

Wockhardt UK Ltd Ash Road North Wrexham LL13 9UF UK

8.    MARKETING AUTHORISATION NUMBER(S)

PL 29831/0359 PA 1339/25/1 MA 154/05101

9.    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

UK: 07/05/2010 Ireland: 16/07/2010 Malta: 22/07/2010

10.    DATE OF REVISION OF THE TEXT 03/2016.

105210/8    Twockhardt