Davis Mellar P, Goforth Harold W
Professor of Medicine, Cleveland Clinic Lerner School of Medicine, Case Western Reserve University, Cleveland, Ohio; Director, Clinical Fellowship Program, Palliative Medicine and Supportive Oncology Services, Division of Solid Tumor, Taussig Cancer Institute, The Cleveland Clinic, Cleveland, Ohio.
Center for Neurological Restoration, Cleveland Clinic, Neurological Institute, Cleveland, Ohio.
J Opioid Manag. 2016 Jan-Feb;12(1):67-85. doi: 10.5055/jom.2016.0313.
The rationale for putting opioid antagonists with an agonist is to improve pain control, to reduce side effects, and/or to reduce abuse. The combination of prolonged release (PR) oxycodone and naloxone reduces constipation as demonstrated in multiple studies and has been designated a tamper-resistant opioid by the Food and Drug Administration. Bioequivalence of the combination product compared with PR oxycodone has not been established. Several of the pivotal studies provided suboptimal laxative support in the control arm of the randomized trials. Two noninferiority trials have demonstrated equivalent analgesia between PR oxycodone and the combination product at doses of less than 120 mg of oxycodone per day. There appears to be an analgesic ceiling above 80-120 mg of oxycodone per day. Safety monitoring during randomized trials was not been well described in published manuscripts. Benefits appear to be better for those with chronic noncancer pain compared with individuals with cancer when constipation was the primary outcome.
将阿片类拮抗剂与激动剂联合使用的基本原理是改善疼痛控制、减少副作用和/或减少药物滥用。多项研究表明，缓释羟考酮和纳洛酮的组合可减少便秘，并且已被美国食品药品监督管理局指定为具有抗篡改功能的阿片类药物。该组合产品与缓释羟考酮相比的生物等效性尚未确定。在随机试验的对照组中，几项关键研究提供的泻药支持并不理想。两项非劣效性试验表明，当每日羟考酮剂量低于120毫克时，缓释羟考酮与该组合产品之间的镇痛效果相当。每天服用80-120毫克以上的羟考酮似乎存在镇痛上限。已发表的手稿中对随机试验期间的安全性监测描述不佳。当以便秘为主要结果时，与癌症患者相比，慢性非癌性疼痛患者似乎受益更大。
