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Increasing severity of pain will require an increased dosage of OxyNorm capsules. 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.
Oxynorm 10mg should be taken at 4-6 hourly intervals. The dosage is dependent on the severity of the pain, and the patient’s previous history of analgesic requirements.
Increasing severity of pain will require an increased dosage of Oxynorm 10mg capsules. 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.
The usual starting dose for opioid naive patients or patients presenting with severe pain uncontrolled by weaker opioids 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.
Conversion from oral morphine:
Patients receiving oral morphine before Oxynorm 10mg 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 10mg capsules required. Inter-patient variability requires that each patient is carefully titrated to the appropriate dose.
A dose adjustment is not usually necessary in elderly patients.
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 plasma concentration in this patient population may be increased. 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.
Oxynorm 10mg capsules should not be used in patients under 18 years.
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.
Method of administration
Oxynorm 10mg capsules are for oral use.
Duration of treatment
Oxycodone should not be used for longer than necessary. In common with other strong opioids, the need for continued treatment should be assessed at regular intervals.
Discontinuation of treatment
When a patient no longer requires therapy with oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.
Hypersensitivity to oxycodone or to any of the excipients listed in section 6.1. Oxycodone must not be used in any situation where opioids are contraindicated: severe respiratory depression with hypoxia, paralytic ileus, acute abdomen, delayed gastric emptying, severe chronic obstructive lung disease, cor pulmonale, severe bronchial asthma, elevated carbon dioxide levels in the blood , moderate to severe hepatic impairment, chronic constipation.
4.4 Special warnings and precautions for use
The major risk of opioid excess is respiratory depression. Caution must be exercised when administering oxycodone to the debilitated elderly; opioid-dependent patients; patients with severely impaired pulmonary function, patients with impaired hepatic or renal function; patients with myxedema, hypothyroidism, Addison’s disease, toxic psychosis, prostate hypertrophy, adrenocortical insufficiency, alcoholism, delirium tremens, diseases of the biliary tract, pancreatitis, inflammatory bowel disorders, hypotension, hypovolaemia, raised increased intracranial pressure, head injury (due to risk of increased intracranial pressure) or patients taking MAO inhibitors.
Oxynorm 10mg capsules should not be used where there is a possibility of paralytic ileus occurring. Should paralytic ileus be suspected or occur during use, Oxynorm 10mg capsules should be discontinued immediately.
Oxynorm 10mg capsules should be used with caution pre-operatively and within the first 12-24 hours post-operatively.
As with all opioid preparations, oxycodone products 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.
Patients about to undergo additional pain relieving procedures (e.g. surgery, plexus blockade) should not receive Oxynorm 10mg capsules for 6 hours prior to the intervention. If further treatment with oxycodone is indicated then the dosage should be adjusted to the new post-operative requirement.
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.
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 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.
The patient may develop tolerance to the drug with chronic use and require progressively higher doses to maintain pain control. Prolonged use of this product 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, mydriasis and palpitations. 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.
Hyperalgesia that will not respond to a further dose increase of oxycodone may occur, particularly in high doses. An oxycodone dose reduction or change to an alternative opioid may be required.
Oxycodone has an abuse profile similar to other strong agonist opioids. Oxycodone may be sought and abused by people with latent or manifest addiction disorders. There is potential for development of psychological dependence [addiction] to opioid analgesics, including oxycodone. Oxynorm 10mg should be used with particular care in patients with a history of alcohol and drug abuse.
As with other opioids, infants who are born to dependent mothers may exhibit withdrawal symptoms and may have respiratory depression at birth.
The capsules should be swallowed whole, and not chewed or crushed.
Abuse of oral dosage forms by parenteral administration can be expected to result in serious adverse events, which may be fatal.
Concomitant use of alcohol and Oxynorm 10mg capsules may increase the undesirable effects of OxyNorm capsules; concomitant use should be avoided.
Sunset yellow, a constituent of the 5mg capsule, can cause allergic-type reactions such as asthma. This is more common in people who are allergic to aspirin.
4.5 Interaction with other medicinal products and other forms of interaction
There can be an enhanced CNS depressant effect during concomitant therapy with drugs which affect the CNS such as tranquillisers, anaesthetics, hypnotics, anti-depressants, sedatives, phenothiazines, neuroleptic drugs, other opioids, muscle relaxants and antihypertensives.
Concomitant administration of oxycodone with anticholinergics or medicines with anticholinergic activity (e.g. tricyclic anti-depressants, antihistamines, antipsychotics, muscle relaxants, anti-Parkinson drugs) may result in increased anticholinergic adverse effects. Oxycodone should be used with caution and the dosage may need to be reduced in patients using these medications.
MAO inhibitors are known to interact with narcotic analgesics. MAO-inhibitors cause CNS excitation or depression associated with hypertensive or hypotensive crisis (see section 4.4).
Alcohol may enhance the pharmacodynamic effects of OxyNorm, concomitant use should be avoided.
Oxycodone is metabolised mainly by CYP3A4, with a contribution from CYP2D6. The activities of these metabolic pathways may be inhibited or induced by various co-administered drugs or dietary elements.
CYP3A4 inhibitors, such as macrolide antibiotics (e.g. clarithromycin, erythromycin and telithromycin), azole-antifungals (e.g. ketoconazole, voriconazole, itraconazole, and posaconazole), protease inhibitors (e.g. boceprevir, ritonavir, indinavir, nelfinavir and saquinavir), cimetidine and grapefruit juice may cause a reduced clearance of oxycodone that could cause an increase of the plasma concentrations of oxycodone. Therefore the oxycodone dose may need to be adjusted accordingly.
Some specific examples are provided below:
• Itraconazole, a potent CYP3A4 inhibitor, administered 200 mg orally for five days, increased the AUC of oral oxycodone. On average, the AUC was approximately 2.4 times higher (range 1.5 – 3.4).
• Voriconazole, a CYP3A4 inhibitor, administered 200 mg twice-daily for four days (400 mg given as first two doses), increased the AUC of oral oxycodone. On average, the AUC was approximately 3.6 times higher (range 2.7 – 5.6).
• Telithromycin, a CYP3A4 inhibitor, administered 800 mg orally for four days, increased the AUC of oral oxycodone. On average, the AUC was approximately 1.8 times higher (range 1.3 – 2.3).
• Grapefruit Juice, a CYP3A4 inhibitor, administered as 200 ml three times a day for five days, increased the AUC of oral oxycodone. On average, the AUC was approximately 1.7 times higher (range 1.1 – 2.1).
CYP3A4 inducers, such as rifampicin, carbamazepine, phenytoin and St John´s Wort may induce the metabolism of oxycodone and cause an increased clearance of oxycodone that could cause a reduction of the plasma concentrations of oxycodone. The oxycodone dose may need to be adjusted accordingly.
Some specific examples are provided below:
• St Johns Wort, a CYP3A4 inducer, administered as 300 mg three times a day for fifteen days, reduced the AUC of oral oxycodone. On average, the AUC was approximately 50% lower (range 37-57%).
• Rifampicin, a CYP3A4 inducer, administered as 600 mg once-daily for seven days, reduced the AUC of oral Oxynorm 10mg. On average, the AUC was approximately 86% lower
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 resulted in an increase in oxycodone Cmax by 11%, AUC by 13%, and t½ elim. by 14%. Also an increase in noroxycodone level was observed, (Cmax by 50%; AUC by 85%, and t½ elim. by 42%). The pharmacodynamic effects of Oxynorm 10mg were not altered.
4.6 Fertility, pregnancy and lactation
Oxynorm 10mg capsules are not recommended for use in pregnancy nor during labour.
There are limited data from the use of Oxynorm 10mg in pregnant women. Infants born to mothers who have received opioids during the last 3 to 4 weeks before giving birth should be monitored for respiratory depression. Withdrawal symptoms may be observed in the newborn of mothers undergoing treatment with Oxynorm 10mg.
Oxynorm 10mg may be secreted in breast milk and may cause respiratory depression in the newborn. Oxynorm 10mg capsules should, therefore, not be used in breast-feeding mothers.
4.7 Effects on ability to drive and use machines
Oxynorm 10mg may impair the ability to drive and use machines. Oxynorm 10mg 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.
• It is an offence to drive while you have this medicine in your body over a specified limit unless you have a defence (called the ‘statutory defence’).
• This defence applies when:
o The medicine has been prescribed to treat a medical or dental problem; and
o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine.
• Please note that it is still an offence to drive if you are unfit because of the medicine (i.e. your ability to drive is being affected).”