OXYNORM Concentrate oral solution Ref.[90500] Active ingredients: Oxycodone

Route of administration

Oral.

Posology

If an immediate release opioid formulation is used as rescue medication in addition to prolonged-release, the need for more than two “rescues” per day could be an indication that the prolonged-release dosage requires upward titration.

Post-operative pain

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

Elderly and adults over 18 years

OxyNorm concentrate should be taken at 4-6 hourly intervals. The dosage is dependent on the severity of the pain, and the sensitivity of the individual patient. The correct dosage per individual patient is the lowest dose which sufficiently controls the pain with no or tolerable side effects. The patient’s previous history of analgesic requirements, their body weight, and sex (higher plasma concentrations are produced in females), should also be taken into account when determining the dose.

Generally, the lowest effective dose for analgesia should be selected. If higher doses are necessary, increases should be made in 25%-50% increments where possible.

Increasing severity of pain will require an increased dosage of OxyNorm concentrate. The correct dosage for any individual patient is that which controls the pain and is well tolerated throughout the dosing period. Patients should be titrated to pain relief unless unmanageable adverse drug reactions prevent this.

Should be taken at 4-6 hourly intervals. The usual starting dose for opioid naïve patients or patients presenting with severe pain uncontrolled by weaker opioids or debilitated elderly patients is 5 mg, 4-6 hourly. The dose should then be carefully titrated, as frequently as once a day if necessary, to achieve pain relief. The majority of patients will not require a daily dose greater than 400 mg. However, a few patients may require higher doses.

It is recommended that patients take the medication in a consistent manner in relation to the timing of meals (see Section 5.2).

The correct dosage per individual is that which controls the pain with no or tolerable side effects.

Treatment goals and discontinuation

Before initiating treatment with OxyNorm concentrate, 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 longer than necessary. See section 4.4 Special warnings and precautions for use regarding the need for close monitoring for development of dependence and abuse.

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 (Nichols et al. 2002). 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.

Conversion from morphine

It must be emphasized that this is a guide to the dose of oxycodone required. Inter-patient variability requires that each patient is carefully titrated to the appropriate dose. Initially, a lower-than-equivalent dose may be advisable.

Oral

Patients receiving oral morphine before oxycodone 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 must be emphasised that this is a guide to the dose of OxyNorm concentrate required. 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.

Patients with renal or hepatic impairment

The recommended adult starting dose should be reduced by 50% (for example a total daily dose of 10mg orally in opioid naïve patients), and each patient should be titrated to adequate pain control according to their clinical situation. The plasma concentration in this patient population may be increased. Therefore, dose initiation should follow a conservative approach. The starting dose for opioid naïve patients is 2.5 mg 6-hourly.

Paediatric population

Opioids must only be used for appropriate indications and prescribed by a specialist experienced in managing severe pain in children, with careful assessments of the benefits and risks.

Adolescents (from 12 years to 18 years)

Dose initiation:

The usual starting dose for opioid-naive patients, patients presenting with severe pain uncontrolled by weak opioids is 5 mg oxycodone hydrochloride at 6-hour intervals. The dose should be carefully titrated, if necessary on a daily basis, until sufficient pain control is achieved.

During this process, the dosing interval of OxyNorm concentrate may be reduced to 4 hours if required.

However, OxyNorm concentrate should not be taken more than 6 times a day.

Patients already receiving opioids may be initiated on higher doses depending on their previous opioid experience.

Children below the age of 12 years

The safety and efficacy of oxycodone in children below 12 years of age has not yet been established. No data available.

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 osteoathritic pain and intervertebral disc disease.

Signs of oxycodone toxicity and overdosage are pin-point pupils, respiratory depression and hypotension. Circulatory failure and somnolence progressing to stupor or deepening coma, skeletal muscle flaccidity, bradycardia and death may occur in more severe cases. Toxic leukoencephalopathy has been observed with oxycodone overdose.

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 2 mg for an adult and 0.01 mg/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.

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.

Additional/other considerations:

• Consider activated charcoal (50 g for adults, 10-15 g for children), if a substantial amount has been ingested within 1 hour, provided the airway can be protected.
• Gastric contents may need to be emptied as this can be useful in removing unadsorbed drug.

Four years.

Do not store above 30°C.

OxyNorm concentrate is supplied in 120 ml amber glass bottles with polyethylene/polypropylene caps. The bottles are packed into cardboard cartons. An oral syringe is also supplied.

OxyNorm concentrate may be mixed with a soft drink for ease of administration and to improve palatability.