ALIVIO

Posology 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) Dose titration 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 minimise the incidence of adverse reactions.

4). Patients already receiving opioids may start treatment with higher doses taking into account their experience with former opioid therapies. For doses not realisable/practicable with this medicinal product, other strengths and medicinal products 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 Alivio prolonged- release tablets after conversion from other opioids, with 50-75% of the calculated oxycodone dose.

Dose adjustment Some patients who take Alivio following a fixed schedule need rapid release analgesics as rescue medication in order to control breakthrough pain. Alivio 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 Alivio. Use of the rescue medication more than twice daily indicates that the dose of Alivio 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 individually balancing efficacy with the tolerance and risk of undesirable effects. Elderly patients A dose adjustment is not usually necessary in elderly patients. Patients with renal or hepatic impairment The plasma concentration in this 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.

Paediatric population Children under 12 years of age Alivio should not be used in children under 12 years of age because of safety and efficacy concerns. Restless legs syndrome (RLS) Oxycodone is indicated for patients suffering from RLS for at least 6 months.

RLS symptoms should be present daily and during daytime (≥ 4 days/week). Oxycodone should be used after failure of previous dopaminergic treatment. Dopaminergic treatment failure is defined as inadequate initial response, a response that has become inadequate with time, occurrence of augmentation or unacceptable tolerability despite adequate doses.

Previous treatment with at least one dopaminergic medicinal product should have lasted in general 4 weeks. A shorter period might be acceptable in case of unacceptable tolerability with dopaminergic therapy. The dosage should be adjusted to the sensitivity of the individual patient.

Treatment of patients with restless legs syndrome with Oxycodone should be under the supervision of a clinician with experience in the management of restless legs syndrome. 5 mg of oxycodone hydrochloride/naloxone hydrochloride at 12 hourly intervals.

Titration on a weekly basis is recommended in case higher doses are required. The mean daily dose in the pivotal study was 20mg/10mg oxycodone hydrochloride/naloxone hydrochloride. Some patients may benefit from higher daily doses up to a maximum of 60 mg/30 mg oxycodone hydrochloride/naloxone hydrochloride.

Oxycodone is taken at the determined dosage twice daily according to a fixed time schedule. While symmetric administration (the same dose mornings and evenings) subject to a fixed time schedule (every 12 hours) is appropriate for the majority of patients, some patients, depending on the individual situation, may benefit from asymmetric dosing tailored to the individual patient.

In general, the lowest effective dose should be selected. For doses not realisable/practicable with this strength other strengths of this medicinal product are available. Restless legs syndrome At least every three months during therapy with Oxycodone patients should be clinically evaluated.

During the initiation of treatment and dose adjustments, more frequent evaluation may be undertaken. Treatment should only be continued if Oxycodone is considered effective and the benefit is considered to […]

Adverse drug reactions are typical of full opioid agonists. 4). Constipation may be prevented with an appropriate laxative. If nausea and vomiting are troublesome, oxycodone may be combined with an anti-emetic. The following frequency categories form the basis for classification of the undesirable effects: Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1,000 to < 1/100) Rare (≥ 1/10,000 to < 1/1,000) Very rare (< 1/10,000) Not known (cannot be estimated from the available data) Immune system disorders Uncommon: hypersensitivity Not Known: anaphylactic response, anaphylactoid response Metabolism and nutrition disorders Common: decreased appetite Uncommon: dehydration Psychiatric disorders Common: anxiety, confusional state, depression, insomnia, nervousness, abnormal thinking, abnormal dreams Uncommon: agitation, affect lability, euphoric mood, hallucinations, decreased libido, disorientation, mood altered, restlessness, dysphoria.

4). Nervous system disorders Very common: somnolence, dizziness, headache. Common: tremor, lethargy, sedation, Uncommon: amnesia, convulsions, hypertonia, hypoaesthesia, involuntary muscle contractions, speech disorder, syncope, paraesthesia, dysgeusia, hypotonia Not known: hyperalgesia, Eye disorders Uncommon: visual impairment, miosis Ear and labyrinth disorders Uncommon: vertigo Cardiac disorders Uncommon: Supraventricular tachycardia, palpitations (as a symptom of withdrawal syndrome) Vascular disorders Uncommon: vasodilation, facial flushing.

Rare: hypotension, orthostatic hypotension. Respiratory, thoracic and mediastinal disorders Common: dyspnoea, bronchospasm, cough decreased. Uncommon: respiratory depression, hiccups.

Not Known:

Central sleep apnoea syndrome Gastrointestinal disorders Very common: constipation, nausea, vomiting Common: abdominal pain, diarrhoea, dry mouth, dyspepsia. Uncommon: gastritis, dysphagia, flatulence, eructation, ileus Not known: dental caries Hepatobiliary disorders Uncommon: increased hepatic enzymes, biliary colic Not known: cholestasis, spasm of spincter of Oddi Skin and subcutaneous tissue disorders Very common: pruritus Common: rash, hyperhidrosis Uncommon: dry skin, exfoliative dermatitis.

Rare: urticaria Renal and urinary disorders Uncommon: urinary retention and ureteral spasm. Reproductive system and breast disorders Uncommon: erectile dysfunction, hypogonadism Not known: amenorrhoea General disorders and administration site conditions Common: asthenia, fatigue Uncommon: chills, pyrexia, malaise, oedema, peripheral oedema, thirst Not known: drug withdrawal syndrome in newborns, opioid tolerance.

g. 8). ‘Not known’ should not be interpreted as an indication of the rarity of the occurrence of opioid tolerance and opioid withdrawal syndrome, but a reflection of the limitations in the available evidence that do not support a precise estimate of frequency.

Drug dependence The frequency above regarding drug dependence reflects the current evidence, including cumulative data from clinical trials and additional post marketing sources, and indicates that the risk of drug dependence with opioids is highly variable depending upon: definition of drug dependence; duration of treatment; dose; individual patient risk factors; and clinical settings.

‘Not known’ should not be interpreted as an indication of the rarity of occurrence of drug dependence, but a reflection of the limitations in available evidence that do not support a precise estimate of frequency. Repeated use of Alivio can lead to drug dependence, even at therapeutic doses.

4 for monitoring and risk reduction interventions). 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.

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g. 5). The primary risk of opioid excess is respiratory depression. Hepatobiliary disorders Oxycodone may cause dysfunction and spasm of the sphincter of Oddi, thus increasing the risk of biliary tract symptoms and pancreatitis. Therefore, oxycodone has to be administered with caution in patients with pancreatitis and diseases of the biliary tract.

Sleep-related breathing disorders Opioids may cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia. In patients who present with CSA, consider decreasing the total opioid dosage. Opioid use increases the risk of CSA in a dose-dependent fashion.

8). 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.

2). The patient should be followed closely for signs and symptoms of respiratory depression and sedation. 5). Alivio tablets must be administered with caution in patients taking MAOIs or who have received MAOIs within the previous two weeks.

Alivio tablets should not be used where there is a possibility of paralytic ileus occurring. Should paralytic ileus be suspected or occur during use, Alivio tablets should be discontinued immediately. Alivio tablets are not recommended for pre-operative use or 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.

g. surgery, plexus blockade) should not receive Alivio tablets for 12 hours prior to the intervention. If further 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.

2 for additional information on treatment goals and discontinuation. 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. To avoid damage to the controlled release properties of the prolonged release, tablets must be swallowed whole, and not divided, broken, chewed or crushed.

9). Alcohol treatment with Alivio tablets is indicated then the dosage should be adjusted to the new post-operative requirement. Alivio 60 mg, 80 mg and 120 mg tablets should not be used in patients not previously exposed to opioids.

These tablet strengths may cause fatal respiratory depression when administered to opioid naïve patients. 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. 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 Alivio.

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 Concomitant use of alcohol and Alivio may increase the […]

1 Oxycodone must not be used in any situation where opioids are contraindicated: • Severe chronic obstructive lung disease • Cor pulmonale • Severe bronchial asthma • Severe respiratory depression with hypoxia • Elevated carbon dioxide levels in the blood • Paralytic ileus • Moderate to severe hepatic impairment • Chronic constipation • Acute abdomen • Delayed gastric emptying