POM: Prescription only medicine
This information is intended for use by health professionals
Patients over 18 years of ageThe dose should be adapted to the condition of the individual patient (pain intensity, suffering, individual reaction). The lowest possible dose providing adequate pain relief should be given. Three transdermal patch strengths are available to provide such adaptive treatment: Bupeaze 35 micrograms/h, Bupeaze 52.5 micrograms/h and Bupeaze 70 micrograms/h.Initial dose selection: patients who have previously not received any analgesics should start with the lowest transdermal patch strength (Bupeaze 35 micrograms/h). Patients previously given a WHO step-I analgesic (non-opioid) or a step-II analgesic (weak opioid) should also begin with Bupeaze 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 Bupeaze and choosing the initial transdermal patch strength, the nature of the previous medicinal product, 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 (Bupeaze 35 micrograms/h). Clinical experience has shown that patients who were previously treated with higher daily doses of a strong opioid (in the dimension of approximately 120 mg oral morphine) may start the therapy with the next higher transdermal patch strength (see also section 5.1).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 Bupeaze must be adapted to the requirements of the individual patient and checked at regular intervals.After application of the first Bupeaze 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 medicinal product (with the exception of transdermal opioids) should be given in the same dose during the first 12 hours after switching to Bupeaze and appropriate rescue medicinal products on demand in the following 12 hours.
Dose titration and maintenance therapyBupeaze should be replaced after 96 hours (4 days) at the latest. For convenience of use, the transdermal patch can be changed twice a week at regular intervals, e.g. always on Monday morning and Thursday evening. 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. At the same time no more than two transdermal patches regardless of the strength should be applied.Before application of the next Bupeaze strength the amount of total opioids administered in addition to the previous transdermal patch should be taken into consideration, i.e. the total amount of opioids required, and the dosage adjusted accordingly. Patients requiring a supplementary analgesic (e.g. for breakthrough pain) during maintenance therapy may take for example 0.2 mg - 0.4 mg buprenorphine sublingual every 24 hours in addition to the transdermal patch. If the regular addition of 0.4 0.6 mg sublingual buprenorphine is necessary, the next strength should be used.
Duration of administrationBupeaze should under no circumstances be administered for longer than absolutely necessary. If long-term pain treatment with Bupeaze is necessary in view of the nature and severity of the illness, then careful and regular monitoring should be carried out (if necessary with breaks in treatment) to establish whether and to what extent further treatment is necessary.
Discontinuation of BupeazeAfter removal of Bupeaze buprenorphine serum concentrations decrease gradually and thus the analgesic effect is maintained for a certain amount of time. This should be considered when therapy with Bupeaze is to be followed by other opioids. As a general rule, a subsequent opioid should not be administered within 24 hours after removal of Bupeaze. For the time being only limited information is available on the starting dose of other opioids administered after discontinuation of Bupeaze.
Elderly patientsNo dosage adjustment of Bupeaze is required for elderly patients.
Patients with renal insufficiencySince the pharmacokinetics of buprenorphine is not altered during the course of renal failure, its use in patients with renal insufficiency, including dialysis patients, is possible.
Patients with hepatic insufficiencyBuprenorphine is metabolised in the liver. The intensity and duration of its action may be affected in patients with impaired liver function. Therefore patients with liver insufficiency should be carefully monitored during treatment with Bupeaze.
Paediatric populationAs Bupeaze has not been studied in patients under 18 years of age, the use of the medicinal product in patients below this age is not recommended.
Method of administrationBupeaze should be applied to non-irritated, clean skin on a non-hairy flat surface, but not to any parts of the skin with large scars. Preferable sites on the upper body are: upper back or below the collar-bone on the chest. Any remaining hairs should be cut off with a pair of scissors (not shaved). If the site of application requires cleansing, this should be done with water. Soap or any other cleansing agents should not be used. Skin preparations that might affect adhesion of the transdermal patch to the area selected for application of Bupeaze should be avoided.The skin must be completely dry before application. Bupeaze is to be applied immediately after removal from the sachet. Following removal of the release liner, the transdermal patch should be pressed firmly in place with the palm of the hand for approximately 30 seconds. The transdermal patch will not be affected when bathing, showering or swimming. Bupeaze should be worn continuously for up to 4 days. After removal of the previous transdermal patch a new Bupeaze transdermal patch should be applied to a different skin site. At least one week should elapse before a new transdermal patch is applied to the same area of skin.
Patients with fever / external heatFever and the presence of heat may increase the permeability of the skin. Theoretically in such situations buprenorphine serum concentrations may be raised during buprenorphine treatment. Therefore on treatment with buprenorphine, attention should be paid to the increased possibility of opioid reactions in febrile patients or those with increased skin temperature due to other causes.The transdermal patch should not be exposed to excessive heat (e.g. sauna, infrared-radiation).
PregnancyThere are no adequate data from the use of buprenorphine in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown.Towards the end of pregnancy high doses of buprenorphine may induce respiratory depression in the new-born infant even after a short period of administration. Chronic administration of buprenorphine during the last three months of pregnancy may cause a withdrawal syndrome in the new-born infant.Therefore administration of Bupeaze is contraindicated during pregnancy.
Breast-feedingBuprenorphine is excreted in human milk. Studies in rats have shown that buprenorphine can inhibit lactation.Bupeaze should not be used during breast-feeding.
FertilityAn effect of buprenorphine on fertility in animals is not known (see section 5.3).
|Immune system disorders|
|Very rare||serious allergic reactions|
|Metabolism and nutrition disorders|
|Uncommon Rare Very rare||confusion, sleep disorder, restlessness psychotomimetic effects (e.g. hallucinations, anxiety, nightmares), decreased libido dependence, mood swings|
|Nervous system disorders|
|Common Uncommon Rare Very rare||dizziness, headache sedation, somnolence concentration impaired, speech disorder, numbness, dysequilibrium, paraesthesia (e.g. pricking or burning skin sensation) muscle fasciculation, parageusia|
|Rare Very rare||visual disturbance, blurring of vision, eyelid oedema miosis|
|Ear and labyrinth disorders|
|Very rare||ear pain|
|Uncommon Rare||circulatory disorders (such as hypotension or, rarely, even circulatory collapse) hot flushes|
|Respiratory, thoracic and mediastinal disorders|
|Common Rare Very rare||dyspnoea respiratory depression hyperventilation, hiccups|
|Very common Common Uncommon Rare Very rare||nausea vomiting, constipation dry mouth pyrosis retching|
|Skin and subcutaneous tissue disorders|
|Very common Common Uncommon Rare Very rare||erythema, pruritus exanthema, diaphoresis rash urticaria pustules, vesicles|
|Renal and urinary disorders|
|Uncommon||urinary retention, micturition disorders|
|Reproductive system and breast disorders|
|General disorders and administration site conditions|
|Common Uncommon Rare Very rare||oedema, tiredness weariness withdrawal symptoms, administration site reactions thoracic pain|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard.
General characteristics of the active substanceBuprenorphine has a plasma protein binding of about 96%.Buprenorphine is metabolised in the liver to N-dealkylbuprenorphine (norbupren-orphine) and to glucuronide conjugated metabolites. 2/3 of the active substance is eliminated unchanged in the faeces and 1/3 eliminated as conjugates of unchanged or dealkylated buprenorphine via the urinary system. There is evidence of enterohepatic recirculation.Studies in non-pregnant and pregnant rats have shown that buprenorphine passes the blood-brain and placental barriers. Concentrations in the brain (which contained only unchanged buprenorphine) after parenteral administration were 2-3 times higher than after oral administration. After intramuscular or oral administration buprenorphine apparently accumulates in the foetal gastrointestinal lumen presumably due to biliary excretion, as enterohepatic circulation has not fully developed.
Characteristics of buprenorphine in healthy volunteersAfter the application of buprenorphine, buprenorphine is absorbed through the skin. The continuous delivery of buprenorphine into the systemic circulation is by controlled release from the adhesive polymer-based matrix system.After the initial application of buprenorphine the plasma concentrations of buprenorphine gradually increase, and after 12-24 h the plasma concentrations reach the minimum effective concentration of 100 pg/ml. From the studies performed with the buprenorphine 35 micrograms/h in healthy volunteers, an average Cmax of 200 to 300 pg/ml and an average tmax of 60-80 h were determined. In one volunteer study, buprenorphine 35 micrograms/h and buprenorphine 70 micrograms/h were applied in a cross-over design. From this study, dose proportionality for the different strengths was demonstrated.After removal of buprenorphine the plasma concentrations of buprenorphine steadily decrease and are eliminated with a half-life of approx. 30 hours (range 22 - 36). Due to the continuous absorption of buprenorphine from the depot in the skin elimination is slower than after intravenous administration.
Pack sizes:Packs containing 3, 4, 5, 6, 8, 10, 12, 16, 18, 20 or 24 individually sealed transdermal patches.Not all pack sizes may be marketed.
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