Adis, a Wolters Kluwer Business, Auckland, New Zealand.
Drugs. 2011 Dec 24;71(18):2491-509. doi: 10.2165/11208250-000000000-00000.
This article reviews the pharmacology, therapeutic efficacy and tolerability profile of the 7-day lower-dose (5, 10 and 20 μg/h) buprenorphine transdermal patch (BuTrans®, Norspan®) in the management of chronic non-malignant pain, with a focus on European labelling for the drug. Buprenorphine is a semi-synthetic opioid analgesic that acts primarily as a partial agonist at the mu opioid receptor. The transdermal formulation provides continuous delivery of buprenorphine, resulting in relatively consistent plasma drug concentrations throughout the 7-day dosing interval. The analgesic efficacy of transdermal buprenorphine in patients with osteoarthritis of the hip and/or knee has been demonstrated in several randomized controlled trials, which have shown the formulation to be equivalent to sublingual buprenorphine, noninferior to prolonged-release tramadol tablets, noninferior to codeine plus paracetamol (acetaminophen) combination tablets (when transdermal buprenorphine was used together with regularly scheduled oral paracetamol) and generally superior to a matching transdermal placebo patch. Transdermal buprenorphine was significantly more effective than placebo in reducing chronic low back pain of at least moderate severity in two randomized, double-blind, crossover trials. Other clinical trials, including a randomized, double-blind, maintenance-of-analgesia study, have also demonstrated the analgesic efficacy of transdermal buprenorphine in patients with chronic non-malignant pain of various causes. In general, serious adverse events with transdermal buprenorphine are similar to those for other opioid analgesics. Transdermal buprenorphine has a ceiling effect for respiratory depression, and the main risk is when it is combined with other CNS depressants. The most frequently reported adverse events with transdermal buprenorphine are headache, dizziness, somnolence, constipation, dry mouth, nausea, vomiting, pruritus, erythema, application site pruritus and application site reactions. Transdermal buprenorphine was better tolerated than sublingual buprenorphine in a 7-week, randomized, double-blind trial in patients with osteoarthritis pain. Nevertheless, as with other opioids, persistence with transdermal buprenorphine therapy is difficult for many patients because of adverse events or other reasons. Thus, transdermal buprenorphine has generally demonstrated good efficacy and tolerability in clinical trials in chronic non-malignant pain, providing effective background analgesia as part of pain management strategies for patients with osteoarthritis, low back pain and other persistent pain syndromes of at least moderate severity. It also has favourable pharmacodynamic and pharmacokinetic properties, which have beneficial clinical implications, most notably the convenience of once-weekly administration and no need for dosage adjustments in the elderly or those with compromised renal function, making it an opioid of choice in these patients, and a useful therapeutic option overall in the management of chronic non-malignant pain.
本文回顾了 7 天低剂量(5、10 和 20μg/h)丁丙诺啡透皮贴剂(BuTrans®,Norspan®)在慢性非恶性疼痛管理中的药理学、疗效和耐受性概况,重点介绍了该药的欧洲标签信息。丁丙诺啡是一种半合成阿片类镇痛药,主要作为 μ 阿片受体的部分激动剂发挥作用。透皮制剂提供丁丙诺啡的持续递送,从而在 7 天给药间隔内使血浆药物浓度相对稳定。几项随机对照试验已经证明,丁丙诺啡透皮制剂在髋和/或膝关节骨关节炎患者中的镇痛疗效与舌下丁丙诺啡相当,不劣于延长释放曲马多片,不劣于可待因加对乙酰氨基酚(扑热息痛)复方片剂(当丁丙诺啡透皮制剂与定期口服对乙酰氨基酚联合使用时),并且通常优于匹配的透皮安慰剂贴片。在两项随机、双盲、交叉试验中,丁丙诺啡透皮制剂在治疗慢性中重度腰痛方面比安慰剂更有效。其他临床试验,包括一项随机、双盲、维持镇痛研究,也证明了丁丙诺啡透皮制剂在各种病因慢性非恶性疼痛患者中的疗效。一般来说,丁丙诺啡透皮制剂的严重不良事件与其他阿片类镇痛药相似。丁丙诺啡透皮制剂对呼吸抑制有封顶效应,主要风险是与其他中枢神经系统抑制剂联合使用时。丁丙诺啡透皮制剂最常报告的不良事件是头痛、头晕、嗜睡、便秘、口干、恶心、呕吐、瘙痒、红斑、贴剂部位瘙痒和贴剂部位反应。在一项为期 7 周的随机、双盲、关节炎疼痛患者试验中,丁丙诺啡透皮制剂的耐受性优于舌下丁丙诺啡。尽管如此,与其他阿片类药物一样,由于不良事件或其他原因,许多患者难以坚持使用丁丙诺啡透皮制剂。因此,丁丙诺啡在慢性非恶性疼痛的临床试验中总体上表现出良好的疗效和耐受性,为骨关节炎、腰痛和其他至少中度严重持续性疼痛综合征患者的疼痛管理策略提供有效的基础镇痛,并且具有有利的药效学和药代动力学特性,这具有重要的临床意义,最显著的是每周一次给药的便利性和无需调整老年人或肾功能受损患者的剂量,使其成为这些患者的阿片类药物选择,并且总体上是慢性非恶性疼痛管理的一种有用的治疗选择。
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