OXYACT Film-coated tablet Ref.[27781] Active ingredients: Oxycodone

Caution should be exercised in:

• elderly or debilitated patients,
• patients with severe impairment of lung,
• patients with impaired liver or kidney function,
• myxoedema, hypothyroidism,
• Addison’s disease (adrenal insufficiency),
• intoxication psychosis (e.g. alcohol),
• prostatic hypertrophy,
• alcoholism, known opioid dependence,
• delirium tremens,
• pancreatitis,
• diseases of the biliary tract, biliary or ureteric colic,
• conditions with increased brain pressure,
• disturbances of circulatory regulation,
• epilepsy or seizure tendency and
• in patients taking MAO inhibitors.

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.

Respiratory depression

The major risk of opioid excess is respiratory depression.

Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs

Concomitant use of Oxyact 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 Oxyact 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).

Paralytic ileus

In case of paralytic ileus or suspicion thereof Oxyact should be discontiuned straight away.

Tolerance and dependence

The patient may develop tolerance to the medicinal product with chronic use and require progressively higher doses to maintain pain control.

Oxycodone hydrochloride has a primary dependence potential. However, when used as intended the risk of developing physical or psychological dependence is markedly reduced. There are no data available on the actual incidence of psychological dependence in chronic pain patients.

Prolonged use of oxycodone hydrochloride 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 withdrawal symptoms. Withdrawal symptoms may include yawning, mydriasis, lacrimation, rhinorrhoea, tremor, hyperhidrosis, anxiety, agitation, convulsions and insomnia.

Hyperalgesia that will not respond to a further dose increase of oxycodone may very rarely occur, particularly in high doses. An oxycodone dose reduction or change to an alternative opioid may be required.

Abuse

Oxycodone has an abuse profile similar to other strong opioid agonists. Oxycodone may be sought and abused by people with latent or manifest addictive disorders. There is potential for the development of psychological dependence [addiction] to opioid analgesics, including oxycodone. Oxyact should be used with particular care in patients with a history of alcohol and drug abuse.

Abuse of oral dosage forms by parenteral administration can be expected to result in serious adverse events, which may be fatal.

Surgical procedures

Special care should be taken when oxycodone is used in patients undergoing bowel-surgery. Opioids should only be administered post-operatively when the bowel function has been restored.

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

Patients with severe hepatic impairment

Patients with severe hepatic impairment should be closely monitored.

Alcohol

The intake of oxycodone hydrochloride with alcoholic beverages has to be avoided as alcohol may enhace the frequency of adverse reactions.

Lactose

Oxyact contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Soya

Oxyact contains soya. If you are allergic to peanut or soya, do not use this medicinal product.

Central nervous system depressants (e.g. sedatives, hypnotics, phenothiazines, neuroleptics, anaesthetics, antidepressants, muscle relaxants, antihistamines, antiemetics) and other opioids or alcohol can enhance the CNS depressant effect of oxycodone, in particular respiratory depression.

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 serotoin 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.

Sedative medicines such as benzodiazepines or related drugs

The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dose and duration of concomitant use should be limited (see section 4.4).

Anticholinergics (e.g. neuroleptics, antihistamines, antiemetics, antiparkinson medicinal products) can enhance the anticholinergic undesirable effects of oxycodone (such as constipation, dry mouth or micturition disorders).

Cimetidine can inhibit the metabolism of oxycodone.

Monoaminoxidase (MAO) inhibitors are known to interact with narcotic analgesics, producing CNS excitation or depression with hyper- or hypotensive crisis. Oxycodone should be used with caution in patients administered MAO-inhibitors or who have received MAO-inhibitors during the last two weeks (see section 4.4).

Clinically relevant changes in International Normalized Ratio (INR) in both directions have been observed in individuals if coumarin anticoagulants are co-applied with Oxyact.

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 medicinal products or dietary elements.

CYP3A4 inhibitors, such as macrolide antibiotics (e.g. clarithromycin, erythromycin and telithromycin), azole-type antifungals (e.g. ketoconazole, voriconazole, itraconazole, and posaconazole), protease inhibitors (e.g. boceprevir, ritonavir, indinavir, nelfinavir and saquinavir), cimetidine and grapefruit juice may reduce the clearance of oxycodone which could result in an increase of oxycodone plasma concentrations. Therefore the oxycodone dose may need to be adjusted accordingly.

Some specific examples are provided below:

• Itraconazole, a potent CYP3A4 inhibitor, administered as 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 as 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 as 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 which could result in a reduction of oxycodone plasma concentrations. The oxycodone dose may need to be adjusted accordingly.

Some specific examples are provided below:

• St John’s 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 oxycodone. On average, the AUC was approximately 86% lower.

Medicinal products 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.

Use of this medicinal product should be avoided to the extent possible in patients who are pregnant or breast-feeding.

Pregnancy

There are limited data from the use of oxycodone 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 newborns of mothers undergoing treatment with oxycodone.

Breast-feeding

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

Fertility

Human data are not available. In animal studies, oxycodone had no adverse effects on fertility (see section 5.3).

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 under the influence of this medicine
• However, you would not be committing an offence (called ‘statutory defence’) if:
  • 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 and
  • It was not affecting your ability to drive safely

Oxycodone can cause respiratory depression, miosis, bronchial spasms and spasms of the smooth muscles and can suppress the cough reflex.

The adverse reactions considered at least possibly related to treatment are listed below by system organ class and absolute frequency. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Very common ≥1/10, Commo ≥1/100 to <1/10n, Uncommon ≥1/1,000 to <1/100, Rare ≥1/10,000 to <1/1,000, Very rare <1/10,000, Frequency unknown – cannot be estimated from the available data

Infections and infestations

Rare: Herpes simplex

Immune system disorders

Uncommon: hypersensitivity

Frequency unknown: anaphylactic responses

Blood and lymphatic system disorders

Rare: lymphadenopathy

Endocrine disorders

Uncommon: syndrome of inappropriate antidiuretic hormone secretion

Metabolism and nutrition disorders

Common: decreased appetite up to loss of appetite

Uncommon: dehydration

Rare: Increased appetite

Psychiatric disorders

Common: Altered mood and personality change (e.g. anxiety, depression), decreased activity, restlessness, psychomotor hyperactivity, nervousness, insomnia, abnormal thinking, confusional state

Uncommon: Agitation, affect lability, euphoric mood, perception disturbances (e.g. hallucinations, depersonalisation), decreased libido, drug dependence (see section 4.4)

Frequency unknown: aggression

Nervous system disorders

Very common: somnolence, dizziness, headache

Common: tremor

Uncommon: amnesia, concentration impaired, convulsions (especially in persons with epileptic disorder or predisposition to convulsions), migraine, hypertonia, hypoaesthesia, involuntary muscle contractions, abnormal coordination, speech disorder, syncope, paraesthesia, dysgeusia

Frequency unknown: hyperalgesia

Eye disorders

Uncommon: visual impairment, miosis

Ear and labyrinth disorders

Uncommon: Hearing impaired, vertigo.

Cardiac disorders

Uncommon: palpitation (in the context of withdrawal syndrome), tachycardia

Vascular disorders

Uncommon: vasodilatation

Rare: hypotension, orthostatic hypotension

Respiratory, thoracic and mediastinal disorders

Common: dyspnoea

Uncommon: Dysphonia, cough, respiratory depression

Gastrointestinal disorders

Very common: constipation, nausea, vomiting

Common: dry mouth, rarely accompanied by thirst and difficulty swallowing; hiccups, abdominal pain, diarrhoea, dyspepsia

Uncommon: dysphagia, oral ulcers, gingivitis, stomatitis, flatulence, eructation, ileus

Rare: gingival bleeding, melaena, tooth disorders

Frequency unknown: dental caries

Hepatobiliary disorders

Uncommon: increase hepatic enzymes

Frequency unknown: cholestasis, biliary colic

Skin and subcutaneous tissue disorders

Very common: pruritus

Common: skin reactions/rash, hyperhidrosis

Uncommon: dry skin

Rare: urticaria

Renal and urinary disorders

Common: Dysuria, micturition urgency

Uncommon: Urinary retention

Reproductive system and breast disorders

Uncommon: reduced libido, erectile dysfunction, hypogonadism

Frequency unknown: amenorrhoea

General disorders and administration site conditions

Common: asthenic conditions

Uncommon: chills, malaise, pain (e.g. chest pain), oedema, peripheral oedema, physical dependence with withdrawal symptoms, drug tolerance, thirst

Rare: weight changes (increase or decrease)

Frequency unknown: drug withdrawal syndrome neonatal

Injury, poisoning and procedural complications

Uncommon: Accidental injury

For infants born to mothers receiving oxycodone see section 4.6.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard, or search for MHRA Yellow Card in the Google Play or Apple App Store.

Not applicable.