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

Initiation of therapy in patients currently not taking opioid analgesics

Patients should start treatment with single doses of 50 mg tapentadol as prolonged-release tablet administered twice daily.

Initiation of therapy in patients currently taking opioid analgesics

When switching from opioids to Palexia SR and choosing the initial dose, the nature of the previous medicinal product, administration and the mean daily dose should be taken into account. This may require higher initial doses of Palexia SR for patients currently taking opioids compared to those not having taken opioids before initiating therapy with Palexia SR.

Titration and maintenance

After initiation of therapy the dose should be titrated individually to a level that provides adequate analgesia and minimises undesirable effects under the close supervision of the prescribing physician.

Experience from clinical trials has shown that a titration regimen in increments of 50 mg tapentadol as prolonged-release tablet twice daily every 3 days was appropriate to achieve adequate pain control in most of the patients.

Total daily doses of Palexia SR greater than 500 mg tapentadol have not yet been studied and are therefore not recommended.

Discontinuation of treatment

Withdrawal symptoms could occur after abrupt discontinuation of treatment with tapentadol (see section 4.8). When a patient no longer requires therapy with tapentadol, it is advisable to taper the dose gradually to prevent symptoms of withdrawal.

Renal Impairment

In patients with mild or moderate renal impairment a dosage adjustment is not required (see section 5.2).

Palexia SR has not been studied in controlled efficacy trials in patients with severe renal impairment, therefore the use in this population is not recommended (see sections 4.4 and 5.2).

Hepatic Impairment

In patients with mild hepatic impairment a dosage adjustment is not required (see section 5.2).

Palexia SR should be used with caution in patients with moderate hepatic impairment. Treatment in these patients should be initiated at the lowest available dose strength, i.e. 50 mg tapentadol as prolonged-release tablet, and not be administered more frequently than once every 24 hours. At initiation of therapy a daily dose greater than 50 mg tapentadol as prolonged-release tablet is not recommended. Further treatment should reflect maintenance of analgesia with acceptable tolerability (see sections 4.4 and 5.2).

Palexia SR has not been studied in patients with severe hepatic impairment and therefore, use in this population is not recommended (see sections 4.4 and 5.2).

Elderly Patients (persons aged 65 years and over)

In general, a dose adaptation in elderly patients is not required. However, as elderly patients are more likely to have decreased renal and hepatic function, care should be taken in dose selection as recommended (see sections 4.2 and 5.2).

Paediatric Patients

The safety and efficacy of Palexia SR in children and adolescents below 18 years of age has not yet been established. Therefore Palexia SR is not recommended for use in this population.

Method of administration

Palexia SR has to be taken whole, not divided or chewed, to ensure that the prolonged-release mechanism is maintained. Palexia SR should be taken with sufficient liquid. Palexia SR can be taken with or without food.

Potential for Abuse and Addiction/ Dependence Syndrome

Palexia SR has a potential for abuse and addiction. This should be considered when prescribing or dispensing Palexia SR in situations where there is concern about an increased risk of misuse, abuse, addiction, or diversion.

All patients treated with active substances that have mu-opioid receptor agonist activity should be carefully monitored for signs of abuse and addiction.

Respiratory Depression

At high doses or in mu-opioid receptor agonist sensitive patients, Palexia SR may produce dose-related respiratory depression. Therefore, Palexia SR should be administered with caution to patients with impaired respiratory functions. Alternative non-mu-opioid receptor agonist analgesics should be considered and Palexia SR should be employed only under careful medical supervision at the lowest effective dose in such patients. If respiratory depression occurs, it should be treated as any mu-opioid receptor agonist-induced respiratory depression (see section 4.9).

Head Injury and Increased Intracranial Pressure

Palexia SR should not be used in patients who may be particularly susceptible to the intracranial effects of carbon dioxide retention such as those with evidence of increased intracranial pressure, impaired consciousness, or coma. Analgesics with mu-opioid receptor agonist activity may obscure the clinical course of patients with head injury. Palexia SR should be used with caution in patients with head injury and brain tumors.

Seizures

Palexia SR has not been systematically eva luated in patients with a seizure disorder, and such patients were excluded from clinical trials. However, like other analgesics with mu-opioid agonist activity 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.

Renal Impairment

Palexia SR has not been studied in controlled efficacy trials in patients with severe renal impairment, therefore the use in this population is not recommended (see section 4.2 and 5.2).

Hepatic Impairment

Subjects with mild and moderate hepatic impairment showed a 2-fold and 4.5-fold increase in systemic exposure, respectively, compared with subjects with normal hepatic function. Palexia SR should be used with caution in patients with moderate hepatic impairment (see section 4.2 and 5.2), especially upon initiation of treatment.

Palexia SR has not been studied in patients with severe hepatic impairment and therefore, use in this population is not recommended (see sections 4.2 and 5.2).

Use in Pancreatic/Biliary Tract Disease

Active substances with mu-opioid receptor agonist activity may cause spasm of the sphincter of Oddi. Palexia SR should be used with caution in patients with biliary tract disease, including acute pancreatitis.

Concomitant treatment with monoamine oxidase inhibitors (MAOI)

Treatment with Palexia SR should be avoided 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 synaptic noradrenaline concentrations which may result in adverse cardiovascular events, such as hypertensive crisis (see section 4.5)

Palexia SR prolonged-release tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption, should not take this medicinal product.

The adverse drug reactions that were experienced by patients in the placebo controlled trials performed with Palexia SR were predominantly of mild and moderate severity. The most frequent adverse drug reactions were in the gastrointestinal and central nervous system (nausea, dizziness, constipation, headache and somnolence).

The table below lists adverse drug reactions that were identified from clinical trials performed with Palexia SR. They are listed by class and frequency. Frequencies are defined as very common (1/10); common (1/100, <1/10); uncommon (1/1,000, <1/100); rare (1/10,000, <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

Clinical trials performed with Palexia SR with patient exposure up to 1 year have shown little evidence of withdrawal symptoms upon abrupt discontinuations and these were generally classified as mild, when they occurred. Nevertheless, physicians should be vigilant for symptoms of withdrawal (see section 4.2) and treat patients accordingly should they occur.

The risk of suicidal ideation and suicides committed is known to be higher in patients suffering from chronic pain. In addition, substances with a pronounced influence on the monoaminergic system have been associated with an increased risk of suicidality in patients suffering from depression, especially at the beginning of treatment. For tapentadol data from clinical trials and post-marketing reports do not provide evidence for an increased risk