ABTARD

4). The dosage depends on the intensity of pain and the patient’s individual susceptibility to the treatment.

The following general dosage recommendations apply:

Adults and adolescents 12 years of age and older Dose titration and adjustment In general, the initial dose for opioid naïve patients is 10 mg oxycodone hydrochloride given at intervals of 12 hours. Some patients may benefit from a starting dose of 5 mg to minimize the incidence of side effects.

Patients already receiving opioids may start treatment with higher dosages taking into account their experience with former opioid therapies. For doses not realisable/practicable with these strengths, other strengths are available. According to well-controlled clinical studies 10-13 mg oxycodone hydrochloride correspond to approximately 20 mg morphine sulphate, both in the prolonged-release formulation.

Because of individual differences in sensitivity for different opioids, it is recommended that patients should start conservatively with Abtard prolonged-release tablets after conversion from other opioids, with 50-75% of the calculated oxycodone dose.

Some patients who take Abtard prolonged-release tablets following a fixed schedule need rapid release analgesics as rescue medication in order to control breakthrough pain. Abtard prolonged-release tablets are not indicated for the treatment of acute pain and/or breakthrough pain.

The single dose of the rescue medication should amount to 1/6 of the equianalgesic daily dose of Abtard prolonged-release tablets. Use of the rescue medication more than twice daily indicates that the dose of Abtard prolonged-release tablets needs to be increased.

The dose should not be adjusted more often than once every 1-2 days until a stable twice daily administration has been achieved. Following a dose increase from 10 mg to 20 mg taken every 12 hours dose adjustments should be made in steps of approximately one third of the daily dose.

The aim is a patient-specific dosage which, with twice daily administration, allows for adequate analgesia with tolerable undesirable effects and as little rescue medication as possible as long as pain therapy is needed. Even distribution (the same dose mornings and evenings) following a fixed schedule (every 12 hours) is appropriate for the majority of the patients.

For some patients it may be advantageous to distribute the doses unevenly. In general, the lowest effective analgesic dose should be chosen. For the treatment of non- malignant pain a daily dose of 40 mg is generally sufficient; but higher dosages may be necessary.

Patients with cancer-related pain may require dosages of 80 to 120 mg, which in individual cases can be increased to up to 400 mg. If even higher doses are required, the dose should be decided individual balancing efficacy with the tolerance and risk of undesirable effects.

Special attention is required with a view to treating the adverse effects of opioids. Abtard prolonged-release tablets should be taken twice daily based on a fixed schedule at the dosage determined. The prolonged-release tablets may be taken with or independent of meals with a sufficient amount of liquid.

Abtard prolonged release tablets must be swallowed whole and not broken, chewed or crushed. Duration of administration Abtard prolonged-release tablets should not be taken longer than necessary. If long- term treatment is necessary due to the type and severity of the illness careful and regular monitoring is required to determine whether and to what extent treatment should be continued.

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. Paediatric population There have been no studies in patients under 12 years of age, therefore oxycodone hydrochloride should not be used in patients under 12 years.

Elderly patients A dose adjustment is not usually necessary in elderly patients. Patients with renal or hepatic impairment The dose initiation should follow a conservative approach in these patients. 2). Risk patients Risk patients, for example patients with low body weight or slow metabolism of medicinal products, should initially receive half the recommended adult dose if they are opioid naïve.

Dose titration should be performed in accordance with the individual clinical situation. 6. Method of administration For oral use.

The commonest undesirable effects of taking oxycodone are nausea and constipation. Both effects are seen in approximately 25-30% of patients following oral administration. If nausea and vomiting are troublesome, oxycodone may be combined with an anti-emetic.

As with other potent opioids, constipation is to be expected. Constipation may be prevented with a laxative. If the opioid-related symptoms persist, the physician should investigate whether the cause lies elsewhere. Except for constipation, the undesirable effects of full opioid agonists tend to wear off as treatment continues.

Notifying the patient of the need to expect adverse effects often makes the adverse effects easier to cope with. 9). Respiratory depression is more likely in elderly, debilitated or opioid- intolerant patients. The sedative effect usually wears off within a few days.

Biliary and ureteral spasms may be observed in patients predisposed to these. Dependency and tolerance are as a rule not problematic in the treatment of severe pain. Clinical studies Common – Very common (>1/100) Increased ADH secretion Rare (≥1/10,000 to <1/1,000) Weight gain/loss Cardiac: Uncommon (≥1/1,000 to <1/100) Palpitations (in connection with withdrawal symptoms) Nervous system: Very common (≥1/10) Somnolence, headache, sedation, dizziness Common (≥1/100 to <1/10) Weakness, tremor, lethargy Uncommon (≥1/1,000 to <1/100) Amnesia, convulsion, hypertonia, cramps, involuntary muscle contractions, speech disorder, syncope, hypoæsthesia, paræsthesia.

Rare (≥1/10,000 to <1/1,000) Epileptic fits, especially in epileptics or patients with a history of convulsions.

Not known Hyperalgesia Eyes:

Common – Very common (>1/100) Miosis Uncommon (≥1/1,000 to <1/100) Impaired vision, visual disturbances Ear and labyrinth Uncommon (≥1/1,000 to <1/100) Vertigo Respiratory tract, thorax and mediastinum Common (≥1/100 to <1/10) Dyspnoea Uncommon (≥1/1,000 to <1/100) Respiratory depression, bronchospasm Gastro-intestinal tract Very common (≥1/10) Constipation, nausea, vomiting Common (≥1/100 to <1/10) Abdominal pain, diarrhoea, dyspepsia, dry mouth.

4). 4) 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. uk/yellowcard or search for MHRA Yellow Card in the google Play or Apple App Store.

Paediatric population Abtard prolonged-release tablets have not been studied in children younger than 12 years of age. The safety and efficacy of the tablets have not been demonstrated and the use in children younger than 12 years of age is therefore not recommended.

Elderly or debilitated patients The major risk of opioid excess is respiratory depression. g. alcohol), prostatic hypertrophy, adrenocortical insufficiency, alcoholism, known opioid dependence, delirium tremens, pancreatitis, diseases of the biliary tract, inflammatory bowel disorders, biliary or ureteric colic, hypotension, hypovolaemia, conditions with increased brain pressure such as head injury, disturbances of circulatory regulation, epilepsy or seizure tendency and in patients taking benzodiazepines or MAO inhibitors.

This medicinal product can suppress the cough reflex. Patients undergoing abdominal surgery 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 with severe hepatic impairment should be closely monitored. Respiratory depression Respiratory depression is the most significant risk induced by opioids and is most likely to occur in elderly or debilitated patients. The respiratory depressant effect of oxycodone can lead to increased carbon dioxide concentrations in blood and hence in cerebrospinal fluid.

In predisposed patients opioids can cause severe decrease in blood pressure. 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. Endocrine system Opioids 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. Drug dependence, tolerance and potential for abuse For all patients, prolonged use of this product may lead to drug dependence (addiction), even at therapeutic doses.

, major depression). Additional support and monitoring may be necessary when prescribing for patients at risk of opioid misuse. 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.

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. Pre-operative use Abtard prolonged release tablets are not recommended for pre-operative use or within the first 12-24 hours post operatively.

Abusive parenteral venous injection In case of abusive parenteral venous injection the tablet excipients may lead to necrosis of the local tissue, infection, increased risk of endocarditis, and valvular heart injury which may be fatal, granulomas of the lung or other serious, potentially fatal events.

Tablets must not be chewed or crushed To avoid damage to the controlled release properties of the tablets the prolonged release tablets must be swallowed whole, and not broken, chewed or crushed. 9). Alcohol Concomitant use of alcohol and oxycodone hydrochloride prolonged-release tablets may increase the undesirable effects of oxycodone hydrochloride; concomitant use should be avoided.

Abtard […]

1. - Severe respiratory depression with hypoxia and/or hypercapnia. - Severe chronic obstructive pulmonary disease (COPD). - Cor pulmonale. - Severe bronchial asthma. - Elevated carbon dioxide levels in the blood. - Paralytic ileus. - Acute abdomen, delayed gastric emptying.