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

As with all narcotics, a reduction in dosage may be advisable in hypothyroidism. Use with caution in opioid-dependent patients, debilitated elderly and in patients with severely impaired respiratory function, sleep apnoea, tolerance, physical dependence, withdrawal, psychological dependence [addiction], abuse profile, history of substance and/or alcohol abuse, head injury, intracranial lesions or raised intracranial pressure, reduced level of consciousness of uncertain origin, alcoholism, constipation, hypotension, hypovolaemia, toxic psychosis, diseases of the biliary tract, pancreatitis, inflammatory bowel disorders, prostatic hypertrophy, adrenocortical insufficiency, acute alcoholism, delirium tremens, severely impaired renal and hepatic function or severe pulmonary disease and debilitated, elderly and infirm patients, myxedema, Addison’s disease, patients taking benzodiazepines, other CNS depressants (including alcohol) or MAO inhibitors (see below and Section 4.5). OxyNorm concentrate should not be used where there is a possibility of paralytic ileus occurring. Should paralytic ileus be suspected or occur during use, OxyNorm concentrate should be discontinued immediately.

As with all opioid preparations, patients about to undergo additional pain relieving procedures (e.g. surgery, plexus blockade) should not receive OxyNorm concentrate 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.

Respiratory depression

The primary risk of opioid excess is respiratory depression.

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 dose-dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage.

Opioid may also cause worsening of pre-existing sleep apnoea (see section 4.8).

CNS depressants co-administration

Concomitant use of oxycodone and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe oxycodone concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.

The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5).

MAOIs

Oxycodone must be administered with caution in patients taking MAOIs or who have received MAOIs within the previous two weeks.

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 be manifest from these hormonal changes.

Oxycodone 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.

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. There is potential for development of psychological dependence (addiction) to opioid analgesics, including oxycodone.

If opioid treatment is considered appropriate for the patient, then the main aim of treatment is not to minimize the dose of opioid but rather to achieve a dose which provides adequate pain relief with a minimum of side effects.

Tolerance and withdrawal

The patient may develop tolerance to the drug with chronic use and require 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.

Opioids are not first-line therapy for chronic non-malignant pain, nor are they recommended as the only treatment. Opioids should be used as part of a comprehensive treatment programme involving other medications and treatment modalities. Patients with chronic non-malignant pain should be assessed and monitored for addiction and substance abuse.

As with other opioids, infants who are born to dependent mothers may exhibit withdrawal symptoms and may have respiratory depression at birth.

Parenteral abuse of dosage forms not approved for parenteral administration can be expected to result in serious adverse events, which may be fatal.

Opioid Use Disorder (abuse and dependence)

Tolerance and physical and/or psychological dependence may develop upon repeated administration of opioids such as oxycodone.

Repeated use of OxyNorm concentrate may 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 OxyNorm concentrate may result in overdose and/or death. The risk of developing OUD is increased in patients with a personal or a 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 OxyNorm concentrate and during the treatment, treatment goals and a discontinuation plan should be agreed with the patient (see section 4.2). 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 behavior (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.

This medicinal product contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium-free’.

This medicinal product contains 1 mg sodium benzoate in each ml. Benzoate salt may increase jaundice in new-born babies (up to 4 weeks old).

Sunset yellow, a constituent of OxyNorm concentrate, can cause allergic-type reactions such as asthma. This is more common in people who are allergic to aspirin.

The concomitant use of opioids with sedative medicines such as benzodiasepines or related drugs increases the risk of sedation, respiratory depression, coma and death because of addictive CNS depressant effect. The dose and duration of concomitant use should be limited (see section 4.4). Drugs which depress the CNS include, but are not limited to: other opioids, gabapentinoids such as pregabalin, anxiolytics, hypnotics and sedatives (incl. benzodiazepines), antipsychotics, antidepressants, phenothiazines and alcohol.

Co-administration with monoamine oxidase inhibitors or within two weeks of discontinuation of their use is inappropriate.

Concomitant 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, diarrhoea). Oxycodone should be used with caution and the dosage may need to be reduced in patients using these medications.

Concomitant administration of oxycodone with anticholinergics or medications with anticholinergic activity (e.g tricyclic antidepressants, antihistamines, antipsychotics, muscle relaxants, anti-Parkinson drugs) may result in increased anticholinergic adverse effects.

Oxycodone, like other opioids, potentiates the effects of 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. Concurrent administration of quinidine, an inhibitor of cytochrome P450-2D6 with a modified release oxycodone tablet, resulted in an increase in oxycodone C_max by 11%, AUC by 13% and t_1/2 elim. by 14%. Also an increase in noroxycodone level was observed, (C_max by 50%; AUC by 85%, and t_1/2 elim. by 42%). The pharmacodynamic effects of oxycodone were not altered. This interaction may be observed for other potent inhibitors of cytochrome P450-2D6 enzyme. Cimetidine and inhibitors of cytochrome P450-3A4 such as ketoconazole and erythromycin may inhibit the metabolism of oxycodone.

OxyNorm concentrate 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.

Oxycodone may be secreted in breast milk and may cause respiratory depression in the newborn. OxyNorm concentrate should therefore not be used in breast-feeding mothers.

Fertility

No human data on the effect of oxycodone on fertility are available. In rats, there was no effect on mating or fertility with oxycodone treatment (see section 5.3).

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. 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:
  • 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.
• 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)."

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 and vomiting are troublesome, oxycodone may be combined with an anti-emetic.

The undesirable effects listed below are classified by body system according to their incidence (common or uncommon). The following frequencies are basis for assessing undesirable effects: Very Common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1000 to <1/100), Rare (≥1/10000 to <1/1000), Very Rare (<1/10000), Not Known (cannot be estimated from the available data).

The undesirable effects listed below are classified by body system according to their incidence. Common adverse drug reactions have an incidence of 21% and uncommon adverse drug experiences have an incidence of <1%.

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 OxyNorm concentrate 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.

Drug dependence

Repeated use of OxyNorm concentrate can 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).

Paediatric population

The frequency, type and severity of adverse reactions in adolescents (12 to 18 years of age) appear similar to those in adults(see section 5.1).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be reported to: Pharmaceutical Services, Ministry of Health, CY-1475, Nicosia, Cyprus, Tel: +357 22608607, Fax: +357 22608669, Website: www.moh.gov.cy/phs.

Not applicable.