Important Safety Information

The primary risk of opioid excess is respiratory depression

Exercise caution when administering oxycodone to elderly or debilitated patients or any patients with

• Severely impaired pulmonary function,
• Impaired hepatic or renal function;
• Myxoedema,
• 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 intracranial pressure,
• Intracranial lesions,
• Head injury (due to risk of increased intracranial pressure),
• Reduced level of consciousness of uncertain origin, sleep apnoea or patients taking benzodiazepines, other CNS depressants (including alcohol) or MAO inhibitors

Opioids may cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia.

Concomitant use of oxycodone and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death. Concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible.

The patient 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).

Oxeltra is not recommended for pre-operative use or within the first 12-24 hours post-operatively.

Oxeltra 80mg tablets should not be used in patients not previously exposed to opioids. This tablet strength may cause fatal respiratory depression when administered to opioid naïve patients.

Patients about to undergo additional pain relieving procedures (e.g. surgery, plexus blockade) should not receive Oxeltra tablets for 12 hours prior to the intervention. If further treatment with Oxeltra tablets is indicated then the dosage should be adjusted to the new post-operative requirement.

Oxeltra tablets must be swallowed whole, and not broken, chewed or crushed. The administration of broken, chewed or crushed controlled release oxycodone tablets leads to a rapid release and absorption of a potentially fatal dose of oxycodone.

Concomitant use of alcohol and Oxeltra may increase the undesirable effects of Oxeltra; concomitant use should be avoided.

Abuse of oral dosage forms by parenteral administration can be expected to result in serious adverse events, such as local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis, and valvular heart injury, which may be fatal.

Oxeltra tablets contain lactose monohydrate (63.20 mg). Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Empty matrix (tablets) may be seen in the stools.

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 manifest from these hormonal changes.

OPIOID USE DISORDER (ABUSE AND DEPENDENCE)

Tolerance and physical and/or psychological dependence may develop upon repeated administration of opioids such as oxycodone. Iatrogenic addiction following therapeutic use of opioids is known to occur.

Repeated use of Oxeltra may lead to Opioid Use Disorder (OUD). Abuse or intentional misuse of Oxeltra 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).

Patients will require monitoring for signs of drug-seeking behaviour (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.

A comprehensive patient history should be taken to document concomitant medications, including over-the-counter medicines and medicines obtained on-line, and past and present medical and psychiatric conditions.

TOLERANCE

Patients may find that treatment is less effective with chronic use and express a need to increase the dose to obtain the same level of pain control as initially experienced. Patients may also supplement their treatment with additional pain relievers. These could be signs that the patient is developing tolerance. The risks of developing tolerance should be explained to the patient.

Overuse or misuse may result in overdose and/or death. It is important that patients only use medicines that are prescribed for them at the dose they have been prescribed and do not give this medicine to anyone else.

Patients should be closely monitored for signs of misuse, abuse, or addiction.

The clinical need for analgesic treatment should be reviewed regularly.

DRUG WITHDRAWAL SYNDROME

Prior to starting treatment with any opioids, a discussion should be held with patients to put in place a withdrawal strategy for ending treatment with oxycodone.

Drug withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction. When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months.

The opioid drug withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.

If women take this drug during pregnancy, there is a risk that their newborn infants will experience neonatal withdrawal syndrome.

HYPERALGESIA

Hyperalgesia may be diagnosed if the patient on long-term opioid therapy presents with increased pain. This might be qualitatively and anatomically distinct from pain related to disease progression or to breakthrough pain resulting from development of opioid tolerance.

Pain associated with hyperalgesia tends to be more diffuse than the pre-existing pain and less defined in quality. Symptoms of hyperalgesia may resolve with a reduction of opioid dose.