Presentation and Status in Health Basket
2 X 5 mg/patch
2 X 10 mg/patch
2 X 15 mg/patch
2 X 20 mg/patch
BuTrans should be administered every 7th day.
BuTrans is not suitable for the treatment of acute pain.
Patients aged 18 years and over: The lowest BuTrans dose (BuTrans 5 μg/h transdermal patch) should be used as the initial dose.
Consideration should be given to the previous opioid history of the patient as well as to the current general condition and medical status of the patient.
Titration: During initiation of treatment with BuTrans, short-acting supplemental analgesics may be required as needed until analgesic efficacy with BuTrans is attained.
The dose of BuTrans may be titrated upwards as indicated after 3 days, when the maximum effect of a given dose is established. Subsequent dosage increases may then be titrated based on the need for supplemental pain relief and the patient’s analgesic response to the patch.
To increase the dose, a larger patch should replace the patch that is currently being worn, or a combination of patches should be applied in different places to achieve the desired dose. It is recommended that no more than two patches are applied at the same time, up to (and including) a maximum total dose of 40 microgram/hour BuTrans. A new patch should not be applied to the same skin site for the subsequent 3-4 weeks. Patients should be carefully and regularly monitored to assess the optimum dose and duration of treatment.
Conversion from opioids: BuTrans can be used as an alternative to treatment with other opioids. Such patients should be started on the lowest available dose (BuTrans 5 μg/h transdermal patch) and continue taking short-acting supplemental analgesics during titration, as required.
Paediatric population: The safety and efficacy of BuTrans in children below 18 years of age has not been established. No data are available.
Elderly: No dosage adjustment of BuTrans is required in elderly patients.
Renal impairment: No special dose adjustment of BuTrans is necessary in patients with renal impairment.
Hepatic impairment: Buprenorphine is metabolised in the liver. The intensity and duration of its action may be affected in patients with impaired liver function. Therefore patients with hepatic insufficiency should be carefully monitored during treatment with BuTrans.
Patients with severe hepatic impairment may accumulate buprenorphine during BuTrans treatment. Consideration of alternate therapy should be considered, and BuTrans should be used with caution, if at all, in such patients.
For method of administration: See prescribing information for full details.
Treatment of moderate to severe opioid responsive chronic pain conditions which are not adequately responding to non-opioid analgesics.
– Patients with known hypersensitivity to the active substance buprenorphine or to any of the excipients.
– Opioid dependent patients and for narcotic withdrawal treatment.
– Conditions in which the respiratory centre and function are severely impaired or may become so.
– Patients who are receiving MAO inhibitors or have taken them within the last two weeks.
– Patients suffering from myasthenia gravis.
– Patients suffering from delirium tremens.
RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS:
– Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
– Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
– Limit dosages and durations to the minimum required.
– Follow patients for signs and symptoms of respiratory depression and sedation.
BuTrans should be used with particular caution in patients with acute alcohol intoxication, head injury, shock, a reduced level of consciousness of uncertain origin, intracranial lesions or increased intracranial pressure, or in patients with severe hepatic impairment.
Buprenorphine may lower the seizure threshold in patients with a history of seizure disorder.
Significant respiratory depression has been associated with buprenorphine, particularly by the intravenous route. A number of overdose deaths have occurred when addicts have intravenously abused buprenorphine, usually with benzodiazepines concomitantly. Additional overdose deaths due to ethanol and benzodiazepines in combination with buprenorphine have been reported.
Since CYP3A4 inhibitors may increase concentrations of buprenorphine, patients already treated with CYP3A4 inhibitors should have their dose of BuTrans carefully titrated since a reduced dosag might be sufficient in these patients.
BuTrans is not recommended for analgesia in the immediate post-operative period or in other situations characterised by a narrow therapeutic index or a rapidly varying analgesic requirement.
Controlled human and animal studies indicate that buprenorphine has a lower dependence liability than pure agonist analgesics. In humans limited euphorigenic effects have been observed with buprenorphine. This may result in some abuse of the product and caution should be exercised when prescribing to patients known to have, or suspected of having, a history of drug abuse or alcohol abuse or serious mental illness.
As with all opioids, chronic use of buprenorphine can result in the development of physical dependence.
Withdrawal (abstinence syndrome), when it occurs, is generally mild, begins after 2 days and may last up to 2 weeks. Withdrawal symptoms include agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal disorders.
BuTrans should not be used at higher doses than recommended.
Serious adverse reactions that may be associated with BuTrans therapy in clinical use are similar to those observed with other opioid analgesics, including respiratory depression (especially when used with other CNS depressants) and hypotension.
Very common: Headache, Dizziness, Somnolence, Constipation, Nausea, Vomiting, Pruritus, Erythema, Application site reaction.
See prescribing information for full details.
BuTrans must not be used concomitantly with MAOIs or in patients who have received MAOIs within the previous two weeks.
Effect of other active substances on the pharmacokinetics of buprenorphine:
Buprenorphine is primarily metabolised by glucuronidation and to a lesser extent (about 30%) by CYP3A4.
Concomitant treatment with CYP3A4 inhibitors may lead to elevated plasma concentrations with intensified efficacy of buprenorphine.
Studies with the CYP3A4 inhibitor ketoconazole did not produce clinically relevant increases in mean maximum (Cmax) or total (AUC) buprenorphine exposure following BuTrans with ketoconazole as compared to BuTrans alone.
The interaction between buprenorphine and CYP3A4 enzyme inducers has not been studied.
Co-administration of BuTrans and enzyme inducers (e.g. phenobarbital, carbamazepine, phenytoin and rifampicin) could lead to increased clearance which might result in reduced efficacy.
Reductions in hepatic blood flow induced by some general anaesthetics (e.g. halothane) and other medicinal products may result in a decreased rate of hepatic elimination of buprenorphine.
BuTrans should be used cautiously with:
Other central nervous system depressants: other opioid derivatives (analgesics and antitussives containing e.g. morphine, dextropropoxyphene, codeine, dextromethorphan or noscapine). Certain antidepressants, sedative H1-receptor antagonists, alcohol, anxiolytics, neuroleptics, clonidine and related substances. These combinations increase the CNS depressant activity.
Benzodiazepines: This combination can potentiate respiratory depression of central origin.
At typical analgesic doses buprenorphine is described to function as a pure mu receptor agonist In BuTrans clinical studies subjects receiving full mu agonist opioids (up to 90 mg oral morphine or oral morphine equivalents per day) were transferred to BuTrans. There were no reports of abstinence syndrome or opioid
withdrawal during conversion from entry opioid to BuTrans.
Pregnancy and Lactation
Pregnancy: There are no or limited amounts of data data from the use of BuTrans in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown.
Towards the end of pregnancy high doses of buprenorphine may induce respiratory depression in the neonate even after a short period of administration. Long-term administration of buprenorphine during pregnancy may cause a withdrawal syndrome in the neonate.
Therefore BuTrans should not be used during pregnancy and in women of childbearing potential who are not using effective contraception.
Breastfeeding: Buprenorphine is excreted in human milk. Studies in rats have shown that buprenorphine may inhibit lactation. Available pharmacodynamic/ toxicological data in animals has shown excretion of buprenorphine
in milk. Therefore the use of BuTrans during lactation should be avoided.
Symptoms: Symptoms similar to those of other centrally acting analgesics are to be expected. These include respiratory depression, sedation, drowsiness, nausea, vomiting, cardiovascular collapse and marked miosis.
Treatment: Remove any patches from the patient’s skin. Establish and maintain a patent airway, assist or control respiration as indicated and maintain adequate body temperature and fluid balance. Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated.
A specific opioid antagonist such as naloxone may reverse the effects of buprenorphine, although naloxone may be less effective in reversing the effects of buprenorphine than other µ-opioid agonists. Treatment with continuous intravenous naloxone should begin with the usual doses but high doses may be required.