OXYCODONE HYDROCHLORIDE 50 mg/ml Solution for injection or infusion Ref.[8078] Active ingredients: Oxycodone

Prior to starting treatment with opioids, a discussion should be held with patients to put in place a strategy for ending treatment with oxycodone in order to minimise the risk of addiction and drug withdrawal syndrome (see section 4.4).

Posology

The dose should be adjusted according to the severity of pain, the total condition of the patient and previous or concurrent medication. The patient’s previous history of analgesic requirements should be taken into account when determining the dose.

Adults

The following starting doses are recommended. Generally, the lowest effective dose for analgesia should be selected. A gradual increase in dose may be required if analgesia is inadequate or if pain severity increases.

Intravenous – Bolus

Dilute in 0.9% saline, 5% dextrose or water for injections. Administer a bolus dose of 1 to 10 mg slowly over 1-2 minutes.

Doses should not be administered more frequently than every 4 hours.

Intravenous – Infusion

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

Intravenous – Patient Controlled Analgesia (PCA)

Dilute 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 5 minutes.

Subcutaneous – Bolus

Dilute in 0.9% saline, 5% dextrose or water for injections. A starting dose of 5 mg is recommended, repeated at 4-hourly intervals as required.

Subcutaneous – 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 naïve patients, titrating gradually according to symptom control. Cancer patients transferring from oral oxycodone may require higher doses (see below).

Conversion from morphine

Patients switching from parenteral morphine to parenteral oxycodone therapy should do so on the basis of a one to one dose ratio. It must be emphasised that this is a guide to the dose of Oxycodone Hydrochloride 50 mg/ml solution for injection or infusion required. Inter-patient variability requires that each patient is carefully titrated to the appropriate dose.

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

The dose initiation should follow a conservative approach in these patients. The recommended adult starting dose should be reduced by 50% (for example a total daily dose of 10 mg orally in opioid naïve patients), and each patient should be titrated to adequate pain control according to their clinical situation.

Paediatric population

There are no data on the use of Oxycodone Hydrochloride 50 mg/ml solution for injection or infusion 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.

Method of administration

Subcutaneous injection or infusion.

Intravenous injection or infusion.

For instruction on dilution of the medicinal product before administration, see section 6.6.

Treatment goals and discontinuation

Before initiating treatment with Oxycodone Hydrochloride 50 mg/ml solution for injection or infusion, 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).

Duration of treatment

Oxycodone should not be used for longer than necessary.

Symptoms

Patients should be informed of the signs and symptoms of overdose and to ensure that family and friends are also aware of these signs and to seek immediate medical help if they occur.

Acute overdose with oxycodone can be manifested by miosis, 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. Toxic leukoencephalopathy has been observed with oxycodone overdose.

Circulatory failure and somnolence progressing to stupor or coma, hypotonia, bradycardia, pulmonary oedema 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

Primary attention should be given to the establishment of a patent airway and institution of assisted or controlled ventilation. The pure opioid antagonists such as naloxone are specific antidotes against symptoms from opioid overdose. Other supportive measures should be employed as needed.

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.

Unopened ampoules: 3 years.

Opened ampoules: The product should be used immediately after opening the ampoule.

Prepared infusion solutions:

Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C.

For instructions on dilution of the medicinal product before administration, see section 6.6.

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 dilution has taken place in controlled and validated aseptic conditions.

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

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

For storage conditions after first opening or dilution of the medicinal product, see section 6.3.

Colourless glass ampoules with a nominal volume of 1 ml.

Pack size: 5, 10 ampoules.

Not all pack sizes may be marketed.

Each ampoule is for single use in a single patient. This medicine should be given immediately after opening the ampoule and any unused portion should be discarded.

The medicinal product should be examined visually and should not be used if particulate matter or discolouration are present.

Oxycodone Hydrochloride 50 mg/ml solution for injection or infusion has been shown to be compatible with the following drugs:

Hyoscine butylbromide
Hyoscine hydrobromide
Dexamethasone sodium phosphate
Haloperidol
Midazolam hydrochloride
Metoclopramide hydrochloride
Levomepromazine hydrochloride
Glycopyrronium bromide
Ketamine hydrochloride

Oxycodone Hydrochloride 50 mg/ml solution for injection or infusion, undiluted or diluted to 3 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 25°C.

The 50 mg/ml injection, whether undiluted or diluted to 3 mg/ml in the infusion fluids and containers detailed above, does not need to be protected from light over a 24 hour period.

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