PRENOTRIX

Posology Patients over 18 years of age The Prenotrix dosage should be adapted to the condition of the individual patient (pain intensity, suffering, individual reaction). The lowest possible dosage providing adequate pain relief should be given.

5 micrograms/h and Prenotrix 70 micrograms/h. Initial dose selection Patients who have previously not received any analgesics should start with the lowest transdermal patch strength Prenotrix 35 micrograms/h. Patients previously given a WHO step-I analgesic (non-opioid) or a step-II analgesic (weak opioid) should also begin with Prenotrix 35 micrograms/h.

According to the WHO recommendations, the administration of a non-opioid analgesic can be continued, depending on the patient's overall medical condition. When switching from a step-III analgesic (strong opioid) to Prenotrix and choosing the initial transdermal patch strength, the nature of the previous medication, administration and the mean daily dose should be taken into account in order to avoid the recurrence of pain.

In general it is advisable to titrate the dose individually, starting with the lowest transdermal patch strength (Prenotrix 35 micrograms/h). 1). To allow for individual dose adaptation in an adequate time period sufficient supplementary immediate release analgesics should be made available during dose titration.

The necessary strength of Prenotrix must be adapted to the requirements of the individual patient and checked at regular intervals. After application of the first Prenotrix transdermal patch the buprenorphine serum concentrations rise slowly both in patients who have been treated previously with analgesics and in those who have not.

Therefore initially, there is unlikely to be a rapid onset of effect. Consequently, a first evaluation of the analgesic effect should only be made after 24 hours. The previous analgesic medication (with the exception of transdermal opioids) should be given in the same dose during the first 12 hours after switching to Prenotrix and appropriate rescue medication on demand in the following 12 hours.

Dose titration and maintenance therapy Prenotrix should be replaced after 72 hours (3 days) at the latest. The dose should be titrated individually until analgesic efficacy is attained. If analgesia is insufficient at the end of the initial application period, the dose may be increased, either by applying more than one transdermal patch of the same strength or by switching to the next transdermal patch strength.

The following adverse reactions were reported after administration of buprenorphine in clinical studies and from post marketing surveillance. 000) Not known (cannot be estimated from the available data) a) The most commonly reported systemic adverse reactions were nausea and vomiting.

b) The most commonly reported local adverse reactions were erythema and pruritus. g. g. pricking or burning skin sensation) Very rare: muscle fasciculation, parageusia Eye disorders Rare: visual disturbance, blurring of vision, eyelid oedema Very rare: miosis Ear and labyrinth disorders Very rare: ear pain Musculoskeletal, connective tissue and bone disorders Common: arthralgia Cardiac/Vascular disorders Uncommon: circulatory disorders (such as hypotension or, rarely, even circulatory collapse) Rare: hot flushes Respiratory, thoracic and mediastinal disorders Common: dyspnoea Rare: respiratory depression Very rare: hyperventilation, hiccups Gastrointestinal disorders Very common: nausea Common: vomiting, constipation Uncommon: dry mouth Rare: pyrosis Very rare: retching Skin and subcutaneous tissue disorders Very common: erythema, pruritus Common: exanthema, diaphoresis Uncommon: rash Rare: urticaria Very rare: pustules, vesicles Renal and urinary disorders Uncommon: urinary retention, micturition disorders Reproductive system and breast disorders Rare: decreased erection General disorders and administration site conditions Common: oedema, tiredness Uncommon: weariness Rare: withdrawal symptoms*, administration site reactions Very rare: thoracic pain *see section c) c) In some cases delayed allergic reactions occurred with marked signs of inflammation.

In such cases treatment with Prenotrix should be terminated. Buprenorphine has a low risk of dependence. After discontinuation of Prenotrix, withdrawal symptoms are unlikely. This is due to the very slow dissociation of buprenorphine from the opiate receptors and to the gradual decrease of buprenorphine serum concentrations (usually over a period of 30 hours after removal of the last transdermal patch).

Buprenorphine is not recommended for analgesia in the immediate post-operative period “Do not use for acute post-operative pain owing to the increased risk of persistent post-operative opioid use (PPOU) and opioid-induced ventilatory impairment (OIVI)”.

Prenotrix must only be used with particular caution in acute alcohol intoxication, convulsive disorders, in patients with head injury, shock, a reduced level of consciousness of uncertain origin, increased intracranial pressure without the possibility of ventilation.

Buprenorphine occasionally causes respiratory depression. Therefore care should be taken when treating patients with impaired respiratory function or patients receiving medicinal products which can cause respiratory depression. Buprenorphine has a substantially lower dependence liability than pure opioid agonists.

In healthy volunteer and patient studies with Prenotrix, withdrawal reactions have not been observed. 8). These symptoms are: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastro- intestinal disorders. 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 Prenotrix.

Repeated use of Prenotrix can lead to OUD. A higher dose and longer duration of opioid treatment can increase the risk of developing OUD. Abuse or intentional misuse of Prenotrix 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 In patients abusing opioids, substitution with buprenorphine may prevent withdrawal symptoms. This has resulted in some abuse of buprenorphine and caution should be exercised when prescribing it to patients suspected of having drug abuse problems.

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