Palexia Sr Range 50 mg/100 mg/150 mg/200 mg/250 mg

PALEXIA SR is indicated for the management of moderate to severe chronic pain that is unresponsive to non-narcotic analgesia.

For use in patients aged 18 years and older.

Posology
The dosing regimen should be individualised according to the severity of pain being treated, the previous treatment experience and the ability to monitor the patient. PALEXIA SR should be taken twice daily, approximately every 12 hours.

Initiation of therapy:
a) Initiation of therapy in patients currently not taking opioid analgesics
Patients should start treatment with single doses of 50 mg PALEXIA SR administered twice a day.
b) Initiation of patients currently taking opioid analgesics
When switching from opioids to PALEXIA SR and choosing the initial dose; the nature of the previous medication, administration and the mean daily dose should be taken into account.

Titration and maintenance
After initiation of therapy the dose should be titrated individually to a level that provides adequate analgesia and minimises side effects under the close supervision of the medical practitioner. A titration regimen in increments of 50 mg PALEXIA SR twice daily every 3 days is appropriate to achieve adequate pain control in most of the patients. Total daily doses of PALEXIA SR greater than 500 mg tapentadol have not been studied and are therefore not recommended.

Discontinuation of treatment
Withdrawal symptoms could occur after abrupt discontinuation of treatment with PALEXIA SR (See Undesirable Effects and Special warnings and precautions for use). When a patient no longer requires therapy with PALEXIA SR, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

Special populations
Renal Impairment
No dosage adjustment is recommended in patients with mild or moderate renal impairment (See Pharmacokinetic properties). PALEXIA SR has not been studied in patients with severe renal impairment, therefore the use in this population is not recommended (See Special warnings and precautions for use and Pharmacokinetic properties and Contraindications).

Hepatic Impairment
No dosage adjustment is recommended in patients with mild hepatic impairment (See Pharmacokinetic properties). PALEXIA SR should be used with caution in patients with moderate hepatic impairment. Treatment in these patients should be initiated at PALEXIA SR 50 mg and not be administered more frequently than once every 24 hours. Further treatment should reflect maintenance of analgesia with acceptable tolerability, to be achieved by either shortening or lengthening the dosing interval (see Special warnings and precautions for use and Pharmacokinetic properties). PALEXIA SR has not been studied in patients with severe hepatic impairment and, therefore, use in this population is not recommended (See Contraindications).

Elderly Patients (persons aged 65 years and over)
Recommended dosing for elderly patients with normal renal and hepatic function is the same as for younger adult patients with normal renal and hepatic function. Because elderly patients are more likely to have decreased renal and hepatic function, care should be taken in dose selection as recommended (See Pharmacokinetic properties).

Paediatric Patients
PALEXIA SR is not recommended for use in children below 18 years of age due to insufficient data on safety and efficacy in this population.

Method of administration
PALEXIA SR should be taken whole with sufficient liquid. PALEXIA SR may be administered with or without food. The shell (matrix) of the tapentadol tablet might not be digested completely and therefore it might still be visible in the patientu2019s stool. This finding has no clinical relevance, since the active ingredient of the tablet will have already been absorbed.

PALEXIA SR is contraindicated:

• in patients with a known hypersensitivity to the active substance, tapentadol, or any component of the product;
• in situations where medicines with u03bc-opioid receptor agonist activity, such as PALEXIA SR, are contraindicated, i.e. patients with respiratory depression and patients with acute or severe bronchial asthma or hypercapnia;
• in any patient who has or is suspected of having paralytic ileus;
• in patients with acute intoxication with alcohol, hypnotics, centrally acting analgesics, or psychotropic medicine (See Interaction with other medicines and other forms of interaction);
• in patients who are receiving MAO inhibitors or who have taken them within the last 14 days (See Interaction with other medicines and other forms of interaction);
• in patients with head injury;
• in severe renal impairment (CrCl < 30 ml/min);
• in severe hepatic impairment;
• in acute pancreatitis;
• in pregnancy and lactation (See Fertility pregnancy and lactation).

Potential for abuse
PALEXIA SR has a potential for abuse. This should be considered when prescribing or dispensing PALEXIA SR in situations where there is concern about an increased risk of misuse, abuse, or diversion. Patients treated with PALEXIA SR should be carefully monitored for signs of abuse and addiction.

Respiratory depression
PALEXIA SR may produce dose-related respiratory depression. Therefore, PALEXIA SR should not be administered to patients with impaired respiratory function. (See Contraindications).

Head Injury and increased intracranial pressure
PALEXIA SR should not be used in patients who may be susceptible to the intracranial effects of carbon dioxide retention, such as those with evidence of increased intracranial pressure, impaired consciousness, or coma. PALEXIA SR may obscure the clinical course of patients with head injury.

Seizures
PALEXIA SR has not been evaluated in patients with a seizure disorder. PALEXIA SR should be prescribed with care in patients with a history of a seizure disorder or any condition that would put the patient at risk of seizures. In addition, PALEXIA SR may increase the seizure risk in patients taking other medicinal products that lower the seizure threshold.

Renal impairment
PALEXIA SR has not been studied in efficacy studies in patients with severe renal impairment, therefore the use in this population is contraindicated (See Posology and method of administration and Pharmacokinetic properties).

Hepatic impairment
A study of PALEXIA SR in subjects with hepatic impairment showed higher serum concentrations than in those with normal hepatic function. PALEXIA SR should be used with caution in patients with moderate hepatic impairment (See Posology and method of administration and Pharmacokinetic properties). PALEXIA SR has not been studied in patients with severe hepatic impairment and, therefore, use in this population is contraindicated (See Posology and method of administration and Pharmacokinetic properties).

Use in pancreatic/biliary tract disease
PALEXIA SR may cause spasm of the sphincter of Oddi. PALEXIA SR should be used with caution in patients with biliary tract disease. PALEXIA SR should not be used in patients with acute pancreatitis (See Contraindications).

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

Lactose warning
PALEXIA SR contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

There have been reports of serotonin syndrome associated with the therapeutic use of PALEXIA in combination with serotoninergic medicinal products such as selective serotonin re-uptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants. Serotonin syndrome is likely when one of the following is observed:

• Spontaneous clonus
• Inducible or ocular clonus with agitation or diaphoresis
• Tremor and hyperreflexia
• Hypertonia and body temperature > 38u00b0C and inducible clonus or ocular clonus.

Signs of serotonin syndrome may be for example confusion, agitation, fever, sweating, ataxia, hyperreflexia, myoclonus and diarrhoea. Withdrawal of the serotoninergic medicinal products usually brings about a rapid improvement. Treatment depends on the nature and severity of the symptoms.

There is no clinical data on the concomitant use of PALEXIA SR with mixed opioid agonist/antagonists (such as pentazocine, nalbuphine) or partial u03bc-opioid agonists. The analgesic effect provided by the u03bc-opioid component of PALEXIA SR may be reduced in such circumstances. Therefore, care should be taken when combining PALEXIA SR with these medicinal products.

PALEXIA SR can induce convulsions and increase the potential for selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, antipsychotics and other medicinal products that lower the seizure threshold to cause convulsions. Patients receiving other u03bc-opioid receptor agonist analgesics, general anaesthetics, phenothiazines or other tranquilisers, sedatives, hypnotics or other CNS depressants (including alcohol and illicit drugs) concomitantly with PALEXIA SR may exhibit additive CNS depression. Interactive effects resulting in respiratory depression, hypotension, profound sedation, or coma may result if these substances are taken in combination with PALEXIA SR. When such combined therapy is contemplated, a reduction of dose of one or both medicines should be considered.

PALEXIA SR is contraindicated in patients who are receiving monoamine oxidase (MAO) inhibitors or who have taken them within the last 14 days due to potential additive effects on norepinephrine (noradrenaline) levels which may result in adverse cardiovascular events (See Contraindications).

Pregnancy
PALEXIA SR should not be used during pregnancy (See Contraindications). Studies in animals have shown CNS depressive effects and delayed postnatal development. Long term maternal use of opioids during pregnancy co-exposes the foetus. The newborn may experience subsequent neonatal withdrawal syndrome (NOWS).

Labour and delivery
The effect of PALEXIA SR on labour and delivery in humans is unknown. PALEXIA SR is not recommended for use in women during and immediately prior to labour and delivery. Due to the u03bc-opioid receptor agonist activity of PALEXIA SR, neonates whose mothers have been taking PALEXIA SR should be monitored for respiratory depression.

Lactation
PALEXIA SR should not be used by mothers who are breastfeeding their infants. PALEXIA SR is excreted in milk.

PALEXIA SR may have a major influence on the ability to drive and use machines, due to the fact that it may adversely affect central nervous system functions (see Undesirable effects). This has to be expected especially at the beginning of treatment, at any change of dosage as well as in connection with alcohol or tranquilisers. Patients should be cautioned as to whether driving or use of machines is permitted.

Approximately 70 % of PALEXIA SR treated patients in the placebo controlled studies experienced adverse drug reactions. The most frequent adverse drug reactions were in the gastrointestinal and central nervous system (nausea, dizziness, constipation, headache and somnolence). Approximately 15 % of PALEXIA SR treated patients with adverse drug reactions discontinued from clinical studies in chronic pain. The information below lists adverse reactions that were identified from clinical trials performed with PALEXIA SR and from post-marketing environment. They are listed by system organ class and frequency. The following terms and frequencies are applied: very common (u2265 1/10); common (u2265 1/100 to < 1/10); uncommon (u2265 1/1,000 to < 1/100); rare (u2265 1/10,000 to < 1/1,000); very rare (< 1/10,000); and not known (cannot be estimated from the available data).

ADVERSE DRUG REACTIONS

System Organ Class

Frequency

Very common

Common

Uncommon

Rare

Unknown

Immune system disorders

Medicine hypersensitivity

Metabolism and nutrition disorders

Decreased appetite

Weight decreased

Psychiatric disorders

Sleep disorder, anxiety, depressed mood, nervousness, restlessness

Abnormal dreams, perception disturbances, disorientation, agitation, confusional state, euphoric mood

Drug dependence, abnormal thinking

Nervous system disorders

Dizziness, headache, somnolence, involuntary muscle contractions, tremor, disturbances in attention

Paraesthesia, hypoaesthesia, balance disorder, sedation, syncope, memory impairment, mental impairment, depressed level of consciousness, dysarthria

Abnormal coordination, pre-syncope, convulsion

Eye disorders

Visual disturbance

Cardiac disorders

Increased heart rate, decreased heart rate, palpitations

Vascular disorders

Flushing

Decreased blood pressure

Respiratory, thoracic and mediastinal disorders

Dyspnoea

Respiratory depression

Gastrointestinal disorders

Nausea, constipation

Vomiting, diarrhoea, dyspepsia

Abdominal discomfort

Impaired gastric emptying

Symptoms include miosis, vomiting, and cardiovascular collapse, consciousness disorders up to coma, convulsions and respiratory depression up to respiratory arrest.

Management of overdosage
Management of overdose should be focused on treating the symptoms of u03bc-opioid receptor agonism. Primary attention should be given to re-establishment of a patent airway and institution of assisted or controlled ventilation when overdose of PALEXIA SR is suspected. Pure opioid antagonists such as naloxone, are specific antidotes to respiratory depression resulting from opioid overdose. Respiratory depression following an overdose may outlast the duration of action of the opioid antagonist. Administration of an opioid antagonist is not a substitute for continuous monitoring of airway, breathing, and circulation following an opioid overdose. If the response to opioid antagonists is suboptimal or only brief in nature, an additional antagonist should be administered as directed by the manufacturer of the product. Gastrointestinal decontamination may be considered in order to eliminate unabsorbed medicine. Gastrointestinal decontamination with activated charcoal may be considered within 2 hours after intake. Before attempting gastrointestinal decontamination, care should be taken to secure the airway.