Rodriguez Ryan W
Ryan W. Rodriguez, Pharm.D., BCPS, is Clinical Assistant Professor, Drug Information Specialist, University of Illinois at Chicago College of Pharmacy, Chicago, IL (
Am J Health Syst Pharm. 2014 Sep 1;71(17):1450-5. doi: 10.2146/ajhp130632.
Off-label uses of the peripheral μ-opioid receptor antagonists alvimopan and methylnaltrexone are reviewed.
Alvimopan is approved by the Food and Drug Administration (FDA) for postoperative ileus after surgeries that include partial bowel resection with primary anastomosis, while methylnaltrexone is approved for the treatment of opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care. Literature describing the off-label use of alvimopan in the treatment of OIC and of methylnaltrexone in postoperative ileus was reviewed and included retrospective studies and prospective Phase II-IV trials. Randomized controlled trials did not demonstrate consistent benefit of alvimopan in OIC nor of methylnaltrexone in postoperative ileus. A greater proportion of patients receiving alvimopan for OIC experienced severe adverse cardiovascular events, leading to a risk evaluation and mitigation strategy and discontinuation of its study in this condition. Data are limited and unreplicated for the off-label use of alvimopan for postoperative ileus in patients undergoing abdominal hysterectomy. Individual studies suggest benefit with methylnaltrexone for OIC in unlabeled populations, including patients with non-cancer-related pain, opioid dependence, opioid sedation, and opioid use after orthopedic surgery; however, confirmatory evaluations have not been performed.
Trials of alvimopan in the FDA-approved use of methylnaltrexone (OIC) indicate potentially serious cardiovascular safety concerns and conflicting findings of efficacy. Similarly, trials of methylnaltrexone in the FDA-approved use of alvimopan (postoperative ileus) consistently showed no benefit. Evaluations of both drugs in their labeled conditions in populations not endorsed in their product labeling have been limited and largely unreplicated.
综述外周μ-阿片受体拮抗剂阿洛司琼和甲基纳曲酮的非标签用途。
阿洛司琼已获美国食品药品监督管理局（FDA）批准用于包括部分肠切除并一期吻合术在内的手术后肠梗阻，而甲基纳曲酮则被批准用于接受姑息治疗的晚期疾病患者的阿片类药物引起的便秘（OIC）。对描述阿洛司琼用于治疗OIC和甲基纳曲酮用于术后肠梗阻的非标签用途的文献进行了综述，包括回顾性研究和前瞻性II-IV期试验。随机对照试验未证明阿洛司琼在OIC治疗中或甲基纳曲酮在术后肠梗阻治疗中具有一致的益处。接受阿洛司琼治疗OIC的患者中，有更大比例经历了严重的不良心血管事件，导致了风险评估和缓解策略，并停止了该药物在此情况下的研究。对于接受腹部子宫切除术的患者，阿洛司琼用于术后肠梗阻的非标签用途的数据有限且未得到重复验证。个别研究表明，甲基纳曲酮对未标记人群的OIC有益，包括患有非癌症相关疼痛、阿片类药物依赖、阿片类药物镇静和骨科手术后使用阿片类药物的患者；然而，尚未进行确证性评估。
阿洛司琼在FDA批准用途（甲基纳曲酮用于治疗OIC）中的试验表明存在潜在的严重心血管安全性问题，且疗效结果相互矛盾。同样，甲基纳曲酮在FDA批准用途（阿洛司琼用于治疗术后肠梗阻）中的试验始终未显示出益处。在其产品标签未认可的人群中，对这两种药物在其标记条件下的评估有限且大多未得到重复验证。
