TAPENTADOL ASPIRE

4). 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. This medicine 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 this medicine 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 this medicine for patients currently taking opioids compared to those not having taken opioids before initiating therapy with this medicine. 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. The 25 mg strength can also be used for dose adjustments to meet individual patient requirements.

Total daily doses of this medicine greater than 500 mg tapentadol have not yet been studied and are therefore not recommended. Duration of treatment Tapentadol should not be used longer than necessary. 2). 2). 2). This medicine should be used with caution in patients with moderate hepatic impairment.

e. 25 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. 2).

2). Elderly patients (persons aged 65 years and over) In general, a dose adaptation in elderly patients is not required. 2). Paediatric Patients The safety and efficacy of this medicine in children and adolescents below 18 years of age has not yet been established.

Therefore, this medicine is not recommended for use in this population. Method of administration This medicine has to be taken whole, not divided or chewed, to ensure that the prolonged-release mechanism is maintained. For oral use. This medicine should be taken with sufficient liquid.

This medicine can be taken with or without food. The shell (matrix) of the tapentadol tablet may not be digested completely and therefore it can be eliminated and seen in the patient’s stool. However, this finding has no clinical relevance, since the active substance of the tablet will have already been absorbed.

Treatment goals and discontinuation Before initiating treatment with tapentadol, a treatment strategy including treatment duration and treatment goals, and a plan for end of the treatment, should be agreed together with the patient, in accordance with pain management guidelines.

During treatment, there should be frequent contact between the physician and the patient to evaluate the need for continued treatment, consider discontinuation and to adjust dosages if needed. When a patient no longer requires therapy with tapentadol, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

4).

The adverse drug reactions that were experienced by patients in the placebo controlled trials performed with this medicine 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 this medicine and from post-marketing environment. They are listed by class and frequency. Frequencies are defined as 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).

4) Delirium** Nervous system disorders Dizziness, Somnolence, Headache Disturbance in attention, Tremor, Muscle contractions involuntary Depressed level of consciousness, Memory impairment, Mental impairment, Syncope, Sedation, Balance disorder, Dysarthria, Hypoaesthesia, Paraesthesia Convulsion, Presyncope, Coordination abnormal Eye disorders Visual disturbance Cardiac disorders Heart rate increased, Heart rate decreased, Palpitations Vascular disorders Flushing Blood pressure decreased Respiratory, thoracic and mediastinal disorders Dyspnoea Respiratory depression Gastrointestinal disorders Nausea, Constipation Vomiting, Diarrhoea, Dyspepsia Abdominal discomfort Impaired gastric emptying Skin and subcutaneous tissue disorders Pruritus, Hyperhidrosis, Rash Urticaria Renal and urinary disorders Urinary hesitation, Pollakiuria Reproductive system and breast Sexual dysfunction disorders General disorders and administration site conditions Asthenia, Fatigue, Feeling of body temperature change, Mucosal dryness, Oedema Drug withdrawal syndrome, Feeling abnormal, Irritability Feeling drunk, Feeling of relaxation * Post-marketing rare events of angioedema, anaphylaxis and anaphylactic shock have been reported.

** Post marketing cases of delirium were observed in patients with additional risk factors such as cancer and advanced age.. Clinical trials performed with this medicine 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.

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. 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.

Tolerance and Opioid Use Disorder (abuse and dependence) Tolerance, physical and psychological dependence, and opioid use disorder (OUD) may develop upon repeated administration of opioids such as tapentadol. A higher dose and longer duration of opioid treatment can increase the risk of developing OUD.

Abuse or intentional misuse of opioids may result in overdose and/or death. g. major depression, anxiety and personality disorders). 2). Before and during treatment the patient should also be informed about the risks and signs of OUD. If these signs occur, patients should be advised to contact their physician.

g. too early requests for refills). This includes the review of concomitant opioids and psycho- active drugs (like benzodiazepines). For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered.

Do not use for acute post-operative pain owing to the increased risk of persistent post- operative opioid use (PPOU). Risk from concomitant use of sedating medicinal products such as benzodiazepines or related substances Concomitant use of this medicine and sedating medicinal products such as benzodiazepines or related substances may result in sedation, respiratory depression, coma and death.

Because of these risks, concomitant prescribing with these sedating medicinal products should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe this medicine concomitantly with sedating medicinal products, the reduction of dose of one or both agents should be considered, and the duration of the concomitant treatment should be as short as possible.

The patients should be followed closely for signs and symptoms of respiratory depression and sedation. 5). Respiratory Depression At high doses or in mu-opioid receptor agonist sensitive patients, this medicine may produce dose-related respiratory depression.

Therefore, this medicine should be administered with caution to patients with impaired respiratory functions. Alternative non-mu-opioid receptor agonist analgesics should be considered and this medicine should be employed only under careful medical supervision at the lowest effective dose in such patients.

9). Do not use for acute post-operative pain owing to the increased risk of opioid-induced ventilatory impairment (OIVI). Head Injury and Increased Intracranial Pressure This medicine 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. This medicine should be used with caution in patients with head injury and brain tumours. Seizures This medicine has not been systematically evaluated in patients with a seizure disorder, and such patients were excluded from clinical trials.

However, like other analgesics with mu-opioid agonist activity this medicine is not recommended in patients with a history of a seizure disorder or any condition that would put the patient at risk of seizures. 5). 2). 5-fold increase in systemic exposure, respectively, compared with subjects with normal hepatic function.

2), especially upon initiation of treatment. 2). Use in Pancreatic/Biliary Tract Disease Active substances with mu-opioid receptor agonist activity may cause spasm of the sphincter of Oddi. This medicine should be used with caution in patients with biliary tract disease, including acute pancreatitis.

Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including central sleep apnoea (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.

Mixed opioid agonists/antagonists Care should be taken when combining this medicine with mixed mu-opioid agonist/antagonists (like pentazocine, nalbuphine) or partial mu-opioid agonists (like buprenorphine). g. temporary buprenorphine discontinuation) should be considered, if administration of full mu-agonists (like tapentadol) becomes necessary in acute pain situations.

On combined use with buprenorphine, higher dose requirements for full mu-receptor agonists have been […]

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