The role of transdermal buprenorphine in the treatment of cancer pain: An expert panel consensus

Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Current Medical Research and Opinion (Impact Factor: 2.65). 06/2009; 25(6):1517-28. DOI: 10.1185/03007990902920731
Source: PubMed


The semi-synthetic opioid, buprenorphine, has the general structure of morphine but differs from it in significant ways, both pharmacologically and clinically. A number of long-term studies have shown effective, long-lasting analgesia in moderate to severe cancer and non-cancer pain, including neuropathic pain, with a low incidence of constipation, nausea, dizziness and tiredness. The treatment of moderate to severe chronic pain has improved as a result of the development of new methods of administration of this substance, particularly the introduction of the transdermal drug delivery system, which offers a number of advantages over the usual oral and parenteral routes.
A panel of experts specialising in palliative care and pain treatment was convened in November 2007 to discuss their clinical experiences with transdermal buprenorphine and other analgesics. The aim was to provide practical guidance on the treatment of cancer pain with transdermal buprenorphine, particularly when there is a need for increasing pain relief leading to high and increasing doses. A literature search on the use of transdermal buprenorphine was carried out for the panel meeting (based on a search of PubMed to November 2007 - since updated by an additional search for the period to February 2009) and a number of case histories were presented and discussed. This commentary article presents this evidence and the consensus findings of the expert panel.
The Panel reached consensus that transdermal buprenorphine was a valuable treatment for chronic cancer pain, including its neuropathic components. A number of general recommendations were made. Large-scale, randomised clinical studies are needed to provide product comparisons on the use of analgesics in the treatment of neuropathic pain although it was recognised that such studies may not be practicable. Data on the treatment of acute and chronic pain should be kept separate in general. Physicians should be made more aware of the problem of hyperalgesic effects of some opioids in long term use. Buprenorphine in contrast has been described to exert an antihyperalgesic effect. The development of analgesic tolerance with some opioids in long term use and the lack of it with buprenorphine requires further studies. The registered dose range of 35-140 microg/h was considered adequate to achieve sufficient pain relief in most patients although some members of the panel presented data showing that increases beyond this dose range provided improved pain relief if slow titration is used. However, it was generally felt that more evidence was needed before this could become generally acceptable.
The consensus was that transdermal buprenorphine has a valuable role to play in the treatment of chronic cancer pain because of its efficacy and good safety and tolerability profile, including a low risk of respiratory depression, a lack of immunosuppression and a lack of accumulation in patients with impaired renal function.

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Available from: Sebastiano Mercadante, Oct 07, 2015
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    • "The mixed agonist and antagonist actions of buprenorphine at ␮-opioid receptors probably contribute to its relatively weak abuse and dependence liabilities, making it an attractive pharmacotherapy for opioid addiction. The use of buprenorphine, as an analgesic for the relief of chronic pain or as a treatment for opioid addiction, has grown in recent years (Knudsen et al., 2009; Pergolizzi et al., 2009). It is surprising that, despite this increased use, the effects of chronically administered buprenorphine remain incompletely characterized . "
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    ABSTRACT: The dual antagonist effects of the mixed-action μ-opioid partial agonist/κ-opioid antagonist buprenorphine have not been previously compared in behavioral studies, and it is unknown whether they are comparably modified by chronic exposure. To address this question, the dose-related effects of levorphanol, trans-(-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide (U50,488), heroin, and naltrexone on food-maintained behavior in rhesus monkeys were studied after acute and chronic treatment with buprenorphine (0.3 mg/kg/day). In acute studies, the effects of levorphanol and U50,488 were determined at differing times after buprenorphine (0.003-10.0 mg/kg i.m.). Results show that buprenorphine produced similar, dose-dependent rightward shifts of the levorphanol and U50,488 dose-response curves that persisted for ≥ 24 h after doses larger than 0.1 mg/kg buprenorphine. During chronic treatment with buprenorphine, the effects of levorphanol, U50,488, heroin, and naltrexone were similarly determined at differing times (10 min to 48 h) after intramuscular injection. Overall, results show that buprenorphine produced comparable 3- to 10-fold rightward shifts in the U50,488 dose-response curve under both acute and chronic conditions, but that chronic buprenorphine produced larger (10- to ≥ 30-fold) rightward shifts in the heroin dose-effect function than observed acutely. Naltrexone decreased operant responding in buprenorphine-treated monkeys, and the position of the naltrexone dose-effect curve shifted increasingly to the left as the time after daily buprenorphine treatment increased from 10 min to 48 h. These results suggest that the μ-antagonist, but not the κ-antagonist, effects of buprenorphine are augmented during chronic treatment. In addition, the leftward shift of the naltrexone dose-effect function suggests that daily administration of 0.3 mg/kg buprenorphine is adequate to produce opioid dependence.
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    • "Recently the findings of an expert panel consensus were published on the role of BUP TDS in the treatment of cancer pain.59 The consensus was that BUP TDS has a valuable role to play in the treatment of chronic cancer pain because of its efficacy and good safety and tolerability profile, including a low risk of respiratory depression, a lack of immunosuppression, and a lack of accumulation in patients with impaired renal function. "
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    ABSTRACT: This paper reviews the current clinical data for the role of transdermal buprenorphine (BUP TDS) in the treatment of diverse acute and chronic pain syndromes. Literature searches were carried out using PubMed (1988 to June 2009). The published findings seem to support hypotheses regarding the rather unique analgesic mechanisms of buprenorphine as compared with pure μ-opioids like morphine and fentanyl. However, the exact mechanism of this analgesic efficacy still remains largely unknown despite recent advances in preclinical pharmacological studies. Such assessments have demonstrated the sustained antihyperalgesic effect of buprenorphine in diverse animal pain models. These findings are supported in a growing number of clinical studies of oral, intrathecal, intravenous, and Bup TDS. This review paper focuses almost entirely on the clinical experience concerning the transdermal administration of buprenorphine, although preclinical aspects are also addressed in order to provide a complete picture of the unique pharmacological properties of this analgesic drug. Mounting evidence indicates the appropriateness of Bup TDS in the treatment of diverse acute and chronic pain syndromes which have been less or not responsive to other opioids. Additionally, BUP TDS seems to hold great promise for other difficult-to-treat (pain) conditions, such as patients in the intensive care setting. However, its use is somewhat tempered by the occurrence of local skin reactions which have been shown to be often therapy resistant. Further studies are certainly warranted to identify even more precisely the clinical syndromes that are most sensitive to buprenorphine treatment, and to compare buprenorphine to other opioids in head-to-head trials of acute and chronic pain conditions.
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