:Introduction:On June 14, 2018, the FDA approved generic buprenorphine/naloxone, as an alternative to the brand Suboxone (FDA,2018). A patient who developed acute withdrawal symptoms when switched from Suboxone to generic buprenorphine/naloxone at the same dosage, with resolution with replacement with brand name Suboxone, is presented. Induction of withdrawal with generic buprenorphine/naloxone has not heretofore been described.Methods:Case Study: A 39-year-old right handed single male presented with a past medical history of intravenous heroin dependence. He was relapse free for 5 years and without change on Suboxone film 8mg/2mg twice daily, and was provided with prescriptions for the same, which was substituted to generic brand Dr. Reddy’s Lab SA buprenorphine HCl/naloxone HCl 8mg/2mg film. After two days on this, one hour after taking generic buprenorphine/naloxone film, symptoms of withdrawal began as manifest by hot flashes, diaphoresis, cold chills, leg cramping, and nausea without vomiting. These were the same symptoms he experienced during his past inpatient withdrawal from opioids. These symptoms recurred every day for an entire week until switching back to brand name Suboxone, whereupon his withdrawal symptoms resolved.Discussion:The mechanism whereby the generic buprenorphine/naloxone combination induced withdrawal symptoms is unclear. It appears that this generic version was either not effectively blocking the mu receptors or the naloxone was inducing a withdrawal state. Possibly the porous nature of the film was such that less of the buprenorphine was absorbed through the mucosa. As a result, less was transferred into the bloodstream, across the blood brain barrier, to the nucleus accumbens, and ultimately on kappa opioid/mu receptor (Centerwatch, 2002). Alternatively, a greater amount of naloxone may have been absorbed transmucosally, thus inducing withdrawal. The absorption may have been normal, but the exact milligram dosage may not be accurate with either too little buprenorphine or too much naloxone. On the other hand, this buprenorphine compound may have been pH sensitive, such that it became inactivated upon exposure to the mildly acidic salivary pH. He could have been malingering this response. Again this is unlikely since he was not given a higher dose of buprenorphine/naloxone, rather the same dose of Suboxone as previously prescribed. It is important that physicians be aware of the possibility for acute withdrawal and increased cravings, which can lead to relapse while using this agent. Further investigation of the efficacy of the generic variant and Suboxone as replacement therapy is warranted.

中文翻译：

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108 警告：通用 Suboxone 不等于名牌

:简介：2018 年 6 月 14 日，FDA 批准了仿制药丁丙诺啡/纳洛酮，作为 Suboxone 品牌的替代品（FDA，2018）。介绍了一名患者在从 Suboxone 转换为相同剂量的通用丁丙诺啡/纳洛酮时出现急性戒断症状，​​并用品牌名称 Suboxone 替代解决。迄今为止，尚未描述用通用丁丙诺啡/纳洛酮诱导戒断。方法：案例研究：一名 39 岁的右手单身男性，既往有静脉注射海洛因依赖的病史。他 5 年无复发，每天两次使用 Suboxone 薄膜 8mg/2mg 没有变化，并为其提供了相同的处方，该处方被通用品牌 Dr. Reddy's Lab SA 盐酸丁丙诺啡/盐酸纳洛酮 8mg/2mg 薄膜替代。在这两天之后，服用通用丁丙诺啡/纳洛酮薄膜一小时后，戒断症状开始表现为潮热、出汗、寒战、腿抽筋和恶心但不呕吐。这些症状与他过去住院期间停用阿片类药物时所经历的症状相同。这些症状每天都会出现，持续整整一周，直到改回品牌名称 Suboxone，然后他的戒断症状消失。讨论：通用丁丙诺啡/纳洛酮组合引起戒断症状的机制尚不清楚。似乎这种通用版本要么没有有效地阻断 mu 受体，要么纳洛酮正在诱导戒断状态。可能薄膜的多孔性使得较少的丁丙诺啡通过粘膜被吸收。结果，更少的东西被转移到血液中，穿过血脑屏障，到达伏隔核，最终到达 kappa 阿片样物质/mu 受体（Centerwatch，2002）。或者，更大量的纳洛酮可能已被经粘膜吸收，从而导致戒断。吸收可能是正常的，但丁丙诺啡过少或纳洛酮过多时，确切的毫克剂量可能不准确。另一方面，这种丁丙诺啡化合物可能对 pH 值敏感，因此在暴露于弱酸性唾液 pH 值时会失活。他可能一直在伪装这个回应。这也是不太可能的，因为他没有得到更高剂量的丁丙诺啡/纳洛酮，而是与之前规定的相同剂量的 Suboxone。重要的是医生要意识到急性戒断和增加渴望的可能性，使用该药剂时可能导致复发。有必要进一步研究通用变体和 Suboxone 作为替代疗法的功效。