丁丙诺
丁丙诺啡透皮贴联合复方亚甲蓝注射液用于肛肠手术术后镇痛的效果
丁丙诺啡透皮贴联合复方亚甲蓝注射液用于肛肠手术术后镇痛的效果曹秋锐;魏保沛;谭英娣;黄志芳;郭金彦【摘要】目的研究丁丙诺啡透皮贴联合复方亚甲蓝注射液用于肛肠手术术后镇痛的效果.方法选取2017年1月-2018年8月于该院择期行肛肠手术的患者160例,随机将其分为研究组(80例)及对照组(80例).对照组术后肛周注射1％复方亚甲蓝2ml+罗哌卡因10ml+注射用水5 ml混合液,在此基础上,研究组加用丁丙诺啡透皮贴剂.观察两组不同时间点疼痛评分、镇静评分,同时比较两组应激激素水平及不良反应发生情况.结果研究组术后6、12及24 h的视觉模拟法(VAS)评分均低于对照组,差异有统计学意义(P＜0.05),而两组Ramsay镇静评分差异无统计学意义(P＞0.05);研究组术后24 h的超敏C反应蛋白(hs-CRP)、血浆皮质醇(COR)、肿瘤坏死因子-α(TNF α)水平均明显低于对照组(P＜0.05);此外,两组不良反应发生情况相仿,组间差异无统计学意义(P＞0.05).结论丁丙诺啡透皮贴联合复方亚甲蓝注射液对肛肠手术患者术后镇痛有良好效果,可明显改善患者术后应激反应,且安全性较佳,值得临床推荐.【期刊名称】《中国医学工程》【年(卷),期】2019(027)004【总页数】4页(P41-44)【关键词】肛肠手术;术后镇痛;丁丙诺啡透皮贴;复方亚甲蓝注射液【作者】曹秋锐;魏保沛;谭英娣;黄志芳;郭金彦【作者单位】广东省江门市五邑中医院肛肠科,广东江门529000;广东省江门市五邑中医院肛肠科,广东江门529000;广东省江门市五邑中医院肛肠科,广东江门529000;广东省江门市五邑中医院肛肠科,广东江门529000;广东省江门市五邑中医院肛肠科,广东江门529000【正文语种】中文【中图分类】R619手术治疗是目前肛肠科疾病如肛瘘、直肠息肉等的主要治疗方为，但由于肛门周围神经末梢丰富和肛门结构及功能的特殊性，手术操作亦引起较大疼痛，且疼痛持续时间往往较长，严重影响患者生活质量。
丁丙诺啡透皮贴剂联合依托考昔对髋膝关节置换术后镇痛的临床研究
丁丙诺啡透皮贴剂联合依托考昔对髋膝关节置换术后镇痛的临床研究【摘要】目的：探讨丁丙诺啡透皮贴剂联合依托考昔对髋膝膝关节置换术后镇痛的临床效果。
方法：选本院105例行髋、膝关节置换手术患者，随机区组，A组33例应用丁丙诺啡透皮贴剂，B组35例应用依托考昔，C组37例两种药物联合应用，对比分析各组镇痛效果的差异。
结果：C组术后VAS评分、PSQI评分均显著低于B组与A组，C组术后Harris评分显著高于B组与A组（P＜0.05）。
各组施药前、施药后8h的各项评分相近，B组与A组各项评分相近（P＞0.05）。
结论：丁丙诺啡透皮贴剂联合依托考昔在髋膝关节置换术后镇痛中的效果显著，有利于促进患者早期康复，值得推广应用。
【关键词】髋膝关节置换术；术后镇痛；康复关节置换术是指用人工制造关节替代具有疼痛及丧失关节功能的关节的手术方法，通常用于髋和膝。
髋、膝关节置换术虽然在重建关节功能等方面效果显著[1]，但术后易发生剧烈疼痛，严重影响手术效果及关节功能恢复。
因此，良好的术后镇痛就显得尤为重要，本文研究中在髋、膝关节置换术后镇痛中应用了丁丙诺啡透皮贴剂联合依托考昔，旨在减轻患者痛苦，确保早期康复锻炼，报道如下。
1资料与方法1.1一般资料选取2015年1月至2015年9月在敦煌市医院及甘肃省中医院骨科行髋、膝关节置换手术的105例手术患者作为研究对象，采用数字随机区组法分为3组，A组33例，男13例，女20例，年龄平均为（66.2±10.4）岁；B组35例，男16例，女19例，年龄平均为（65.8±9.1）岁；C组37例，男15例，女22例，年龄平均为（68.1±11.2）岁；本组纳入对象全部自愿参与本次研究并签署镇痛知情同意书，排除对麻醉或镇痛药物具有明显依耐性及合并严重器官功能不全等患者。
各组一般资料对比P＞0.05，差异无明显统计学意义，具有可比性。
1.2方法各组均根据患者病情对所选关节实施相应手术，包括全膝关节置换术、全髋人工关节置换术、人工股骨头置换术，术后各均常规给予地佐辛注射液静脉滴注，具体如下。
丁丙诺啡透皮贴剂超前镇痛对老年全膝关节置换术后镇痛效果的研究
丁丙诺啡透皮贴剂超前镇痛对老年全膝关节置换术后镇痛效果的研究目的观察应用丁丙诺啡透皮贴剂超前镇痛对老年全膝关节置换术后的镇痛效果。
方法选择拟行硬膜外麻醉下全膝关节置换术患者100例，随机分为丁丙诺啡透皮贴剂超前镇痛组（试验组）和术后镇痛组（对照组）两组，每组50例。
试验组于术前2d使用丁丙诺啡透皮贴剂，术后使用帕瑞昔布钠40mg 静脉推注bid；对照组术前给予与丁丙诺啡透皮贴剂相似的空白贴剂，术后使用静脉自控镇痛泵及帕瑞昔布钠40mg 静脉推注bid。
记录每例患者术后12 h、24 h、48 h、72 h的视觉模拟评分（V AS）、术后追加盐酸曲马多及盐酸哌替啶用量和发生不良反应的例数，术后48h患者满意度、术后72h患者的KSS评分，并进行统计学分析。
结果两组患者术后V AS评分、KSS评分、术后追加盐酸曲马多及盐酸哌替啶用量无统计学差异（P>0.05）；试验组的不良反应率低于对照组；试验组的患者满意度高于对照组（P＜0.05）。
结论同术后使用静脉自控镇痛泵相比，丁丙诺啡透皮贴剂超前镇痛对老年全膝关节置换术后镇痛效果满意，且不良反应少，提高了患者的满意度。
标签：丁丙诺啡透皮贴剂；超前镇痛；全膝关节表面置换术随着世界范围内人口老龄化的发展，骨性关节炎的发病率逐年增高。
该病的致残率较高，给患者和社会带来无尽的痛苦和沉重的负担[1]。
人工全膝关节置换术（TKA）是治疗老年膝关节晚期骨性关节炎的有效方法[2]。
随着患者人们对生活质量的重视，TKA手术也被越来越多的患者所接受。
然而术后急性期疼痛严重影响患者术后生理状态及关节功能康复[3]。
术后良好的镇痛不仅能提高患者满意度，还有利于关节的功能恢复、减少住院时间，并可降低血栓等相关并发症风险[4]。
因此TKA围手术期的镇痛始终是临床医师关注的焦点，一直以来人们都在不断探索着更优的镇痛方法。
丁丙诺啡透皮贴剂是一种含丁丙诺啡的经皮给药制剂，可通过限速膜以稳定的速率使药物持续释放并经皮吸收进入循环系统，具有较高的生物利用率，可提供较为稳定的血药浓度而达到较好的镇痛效果，没有创伤性，目前主要用于癌痛治疗，在骨科围术期镇痛领域的相关研究较少[5]。
盐酸丁丙诺啡舌下片
盐酸丁丙诺啡舌下片【适用症】盐酸丁丙诺啡舌下片适用于各种术后疼痛、癌性疼痛、烧伤、肢体痛、心纹痛等。
作用持续时间6～8小时。
也可作为戒瘾的维持治疗。
【注意事项】1. 盐酸丁丙诺啡舌下片为国家特殊管理的第一类精神药品，有一定依赖性，必须严格遵守国家对精神药品的管理条例，按规定开写精神药品处方和供应、管理本类药品，防止滥用。
2. 颅脑损伤及呼吸抑制病人慎用。
【用法与用量】舌下含服。
每次0.2～0.8mg。
每隔6～8小时一次。
【禁忌症】轻微疼痛或疼痛原因不明者不宜应用。
【儿童用药注意事项】7岁以下儿童不宜使用。
【孕妇、哺乳期妇女用药注意事项】盐酸丁丙诺啡舌下片可通过胎盘和血-脑脊液屏障，孕妇、哺乳期妇女不宜使用。
【老年人用药注意事项】老弱病人慎用。
【不良反应】不良反应类似吗啡。
常见不良反应有头晕、嗜睡、恶心、呕吐等。
在使用其它阿片类药物的基础上使用可能有戒断症状。
【药物相互作用】与单胺氧化酶抑制剂有协同作用。
【药理】盐酸丁丙诺啡舌下片为部分μ受体激动药，属激动--拮抗药。
镇痛作用强于哌替啶、吗啡。
与μ受体亲合力强，故可置换出结合于μ受体的其他麻醉性镇痛药，从而产生拮抗作用。
其起效慢，持续时间长。
对呼吸有抑制作用，但临床未见严重呼吸抑制发生。
也能减慢心率、使血压轻度下降，对心排血量无明显影响，药物依赖性近似吗啡。
可通过胎盘和血-脑脊液屏障。
对大鼠的慢性毒性研究表明，盐酸丁丙诺啡舌下片对重要器官未发现明显的毒性作用，无致突变作用和生殖毒性。
【药物代谢动力学】盐酸丁丙诺啡舌下片（舌下含片）主要经颊部黏膜吸收。
血浆蛋白结合率为96%，消除T1/2为1.2～7.2小时不等。
血药浓度与镇痛效果无明显相关性。
盐酸丁丙诺啡舌下片在肝脏部分代谢为N-脱烷基丁丙诺啡（N-dealkylbuprenorphine）及共轭化合物。
大部分（2/3）经粪便以原形排泄，有迹象表明其中部分进入肠肝循环。
经尿液排出的原形物较少，主要为代谢产物。
丁丙诺啡透皮贴剂治疗中重度慢性疼痛的疗效及安全性观察
１ ４ １ ４・
浙江临床医学２ ０ １ ５ 年８ 月第１ ７ 卷第 ８ 期
丁丙诺啡透皮贴剂治疗中重度慢性疼痛的疗效及安全
邓硕 曾振 华 戴仪 顾 新珠
【 摘要 】 目的 观察丁丙 诺啡透皮贴剂治 疗中 重度慢性持续性疼痛的临床疗效与不良 反应。方法 观察８ ０ ４ ￣ １ 中 重 度慢性疼痛患者 使用丁丙
３ 讨论
疼痛是 患者最常见 的就诊原 因之一。根据疼 痛时
组 患者 中 ，中度疼痛 ６ ２ 例 （ ７ ７ ． ５ ％） ，重 度疼 痛 １ ８ 例
（ ２ ２ ． ５ ％） 。
间可分为急性疼痛和慢性疼痛 ，其 中以病程 ＞ １ 个 月的
慢性 疼痛最 为常见 ，对其处 理是 目前 临床上面 临的难 题 。随着 疼痛学研 究 的不 断深入 ，人们越 来越重 视控 制疼 痛 的重要性 ，其 中药 物治疗是大 多数患者最 基本 的治疗 ，在慢性疼 痛治疗 中更 加关 注镇 痛药物 的有效 性 ，能够打断疼 痛 的恶性循 环 ，以及长期 服用 的耐受
度３ ８例 （ ４ ７ ． ５ ％） ，Ｉ Ｖ度 ２ ２ 例 （ ２ ７ ． ５ ％ ｏ全 组总 缓解 率为 ９ ７ ． ５ ％。不 良反 应 ： 丁丙 诺 啡透皮贴 剂 的不 良反 应较轻 ，主要表现 为恶心 、呕吐 、便秘 、头晕 、皮肤
反应 、嗜睡 、排尿困难 、呼吸抑制等 ，见表 １ 。
性 和安全性 。传 统治疗 中 ，非 甾体类抗 炎药物得 到 了 广 泛 的应用 ，但 此类药 物存在多种 不 良反应 ，长期使
用 尤其 明显 ，据报道 ，总发生率 为 ２ ０ ％～ ３ ０ ％。尽管 近年来 ，出现了 Ｃ Ｏ Ｘ 一 ２的特异性抑制剂 ，显著地降低 了 胃肠道并发症 的发生率 … １ ，但是其对 肾脏 、心血管 、 骨髓 和凝 血等系统 的影 响仍然值得关注 。 丁丙诺 啡透皮贴剂是一 种可透过皮肤 吸收 的新 型
丁丙诺啡透皮贴对中晚期恶性肿瘤疼痛的临床有效性观察
丁丙诺啡透皮贴对中晚期恶性肿瘤疼痛的临床有效性观察摘要】目的：讨论丁丙诺啡透皮贴对晚期癌症患者进行治疗的临床效果。
方法：对2015年2月～2016年2月期间我科收治的64例伴有中度以上疼痛症状的晚期癌症患者的临床资料进行回顾性研究。
我科使用丁丙诺啡透皮贴对这64例患者进行了治疗。
治疗结束后，观察这64例患者治疗的效果和治疗前后VAS（视觉模拟疼痛评分法）的评分情况。
结果：经过治疗，这64例患者中治疗结果为显效者有24例，治疗结果有效者有39例，治疗结果无效的患者有1例，治疗总有效率98﹪。
这64例患者治疗前的VAS评分为6.16±0.61分，其治疗后的VAS评分2.53±0.31分。
这64例患者治疗后的VAS评分明显低于治疗前，二者相比差异具有显著性（P﹤0.05）。
在治疗期间，这64例患者出现的不良反应均较轻微，不影响其治疗的效果。
结论：用丁丙诺啡透皮贴对晚期癌症患者进行镇痛治疗效果好，安全性高。
此疗法值得在临床上推广使用。
【关键词】晚期癌症患者；丁丙诺啡透皮贴；镇痛治疗；效果【中图分类号】R730.5 【文献标识码】A 【文章编号】1007-8231（2016）11-0119-02疼痛是继血压、脉搏、体温、呼吸之后的第五大生命体征。
疼痛为癌性患者最常见和最难忍受的症状之一，临床上将此类疼痛叫做癌性疼痛[1]。
癌症晚期的患者多伴有不同程度的疼痛，疼痛从心理、生理、精神和社会多个方面影响病人的生存质量，寻找有效的镇痛方法是疼痛病人非常迫切的愿望。
在临床工作中口服制剂和注射剂是最为常用剂型，但它们存在若干缺点，口服剂型须经胃肠道吸收才能发挥作用，容易被胃酸破坏，有的药物还需经肝代谢，会因此失去活性。
注射剂常引起疼痛，产生的不良反应可能较大。
而透皮帖制剂是在皮肤表面给药，使药物以恒定或接近恒定速度通过皮肤进入人体血液循环，产生全身或局部治疗作用。
丁丙诺啡透皮贴剂具有丁丙诺啡的一般药理性能，且血药浓度稳定、镇痛时间长、呼吸抑制和其他不良反应较小的特点[2]。
丁丙诺啡, 纳洛酮注射液超快速脱毒的临床研究
住 院 自愿 戒 毒 并 同 意进 行 ＮＬ 冲击 治 疗 者 ， 合 Ｘ 符
Ｃ ＭＤ ３海 洛 因依 赖 综 合 征 诊 断 标 准 。年 龄 ‘ ～ Ｃ － １ ８ ４ ， 体格 检查 和实 室检 查 ， 除躯体 疾 病 ， 染 ５岁 经 排 传
病 和神经精 神病者 。按入 院先后 顺序 随机分 为 Ａ， Ｂ
［ ｅ ｏｄ］ ｈ ｒｉ ｄ ｐｎ ｅ ｃ／ Ｔ； ｂ ｐｅｏｐ ｉｅＡＤ； ｎ ｌｘ ｎ／ － ｙｗ ｒｓ Ｋ ｅｏｎ ｅ ｅｄｎ ｅＤ ｕ ｒｎｒｈｎ ／ ａ ｏ ｅＡＤ ｏ ［ 图分 类 号 ］ Ｒ ４ ． １ ［ 中 ７９６ 文献 标 识 码 ］ Ａ ［ 章 编 号 ］ １ ７—１ １２ ０ ）２０ ９ 。９—３ 文 ６ １７ ７ （０ ９ ０—２ ２２ ６０
ｐ ｅ ｏ ｐ ｉ ｅ ｃ ｎ ｒ ｄ ｃ ｔ ｄ ａ ｌｓ ｍｐ ｏ ｎ ｉ ｅ ｅ ｆ ｃｓ ｏ ａ ｉ ｎ ｉ ｈ ｄ ｓ ｒ ｎ ｒ ｈ ｎ ａ ｅ ｕ ｅｗｉ ｒ ｗａ ｙ ｔ ｍｓ ａ ｄ ｓｄ ｆｅ ｔ ｆｒ ｐ ｄ ａ ｈ ｇ ｏ ｅ ＮＬＸ． Ｉ ａ ｍｐ ｒａ ｔ ｈ ｄ ｔｈ ｓ ｉ ｏ ｔ ｎ ＂ ｃｉ ｉａ ａｕ ｔ ｒ ａ ｅ ｌ ｃ ｌ ｌ ｅｗｉ ｍｏ ｅ ｓ ｆ ． ｎ ｖ ｈ
ｔｅ ａ ｙ Ｒｅ ｕｔ］ ｅｓｄ ｆｅｔ ｎ ｔ ｄ ａ ｌｓｍｐ ｏ ｒ ｅ ｒａ ｅ ｉｎｆ ａ ｔ ｒ ｕ （Ｐ＜Ｏ ｈ ｒ ｐ ．［ ｓ ｌｓ Ｔｈ ｉｅｅｆｃｓａ ｄｗｉ ｒ ｗａ ｙ ｔｍｓｗｅｅｄ ｃｅ ｓｄ ｓｇ ｉｃ ｎ ｌ ｉ ｇ ｏ ｐＡ ｈ ｉ ｙｎ ．
者 为 Ｂ组 ， ３ 各 Ｏ例 。 两 组在 冲击 治疗 期 间 及 次 日均 静 脉 输 氧 一 次 。每 天 进 行 戒 断 症 状 与 不 良反 应 的观 察 与
丁丙诺啡透皮贴剂治疗癌痛患者的临床疗效及安全性评价
丁丙诺啡透皮贴剂治疗癌痛患者的临床疗效及安全性评价王淳;李建强;王红胜【摘要】目的研究丁丙诺啡透皮贴剂治疗癌痛患者的临床疗效及安全性.方法 60例癌性疼痛患者,采用随机数字表法分为对照组和观察组,各30例.对照组采取芬太尼透明皮贴剂治疗,观察组采取丁丙诺啡透皮贴剂治疗,比较两组治疗前后的疼痛视觉模拟评分(VAS)和不良反应发生情况.结果治疗前,两组患者VAS评分比较,差异无统计学意义(P>0.05);观察组治疗后VAS评分(2.49±0.32)分,明显低于对照组的(3.52±0.23)分,差异具有统计学意义(P<0.05).观察组治疗后不良反应发生率明显低于对照组,差异具有统计学意义(P<0.05).结论丁丙诺啡透皮贴剂可明显减低癌性疼痛患者的VAS评分,临床疗效显著,不良反应发生率低,值得推广.【期刊名称】《中国现代药物应用》【年(卷),期】2018(012)015【总页数】2页(P104-105)【关键词】丁丙诺啡透皮贴剂;芬太尼透明皮贴剂;癌性疼痛【作者】王淳;李建强;王红胜【作者单位】528425 广东省中山市东凤人民医院;528425 广东省中山市东凤人民医院;528425 广东省中山市东凤人民医院【正文语种】中文癌性疼痛是指疼痛组织或部位因需调节或修复的信息传递至中枢神经引起的疼痛感觉, 在癌症中晚期患者群体中较为多见。
90%以上的癌性疼痛主要来自于肿瘤直接引起的疼痛, 而由癌症治疗所致的间接性癌性疼痛则较为少见。
有研究指出［1］, 除了癌症引起的躯体生理性疼痛, 心理、社会和精神性等因素均可导致癌性疼痛。
临床上常采用三阶梯疗法针对性治疗不同程度的癌痛患者, 轻度癌性疼痛一般采用非阿片类, 中度采用弱阿片类, 重度疼痛则采用强阿片类镇痛给药, 而研究表明服用上述药物可引起恶心呕吐、免疫力下降、药物依赖等不良反应［2］。
透明贴剂具有无肝脏首过效应、生物利用度高等优点, 因此本研究作者通过研究丁丙诺啡透皮贴剂治疗癌痛患者的临床疗效及安全性评价, 旨在为临床提供指导。
丁丙诺啡透皮贴剂治疗骨科中重度慢性疼痛的效果
·临床医学系统研究·系统医学SYSTEMS MEDICINE 系统医学2021年2月第6卷第4期在骨科中疼痛是一种非常常见的临床问题,如果患者的疼痛感在初始阶段没有得到有效控制,在持续强烈的疼痛刺激下,有可能会导致患者的中枢神经系统出现病理性变化,最终导致出现很难控制的慢性疼痛[1]。
中重度慢性疼痛会对患者的身体健康和日常工作生活造成极大的影响,在严重的情况下甚至会致残。
为了缓解患者的疼痛感,保证其生活质量,必须要采用合理的镇痛方案对患者进行治疗。
现在临床上很多镇痛药物具有较好的镇痛效果,但是如果长期服用很容易导致患者出现依赖性和耐受性,引起各种不良反应。
作为一种阿片类镇痛药物,丁丙诺啡制作的透皮贴具有非常显著的镇痛效果,而且不良反应少,因此在临床中得到了较多的应用。
对此,该文选择2018年12月—2019年12月该院收治的相关病例86例,分析并研究了骨科中重度慢性疼痛患者采用丁丙诺啡透皮贴剂治疗的效果,现报道如下。
1资料与方法1.1一般资料选择该院收治的骨科中重度疼痛患者86例作为该次研究对象,按照随机数表法将其划分为甲组和乙DOI:10.19368/ki.2096-1782.2021.04.052丁丙诺啡透皮贴剂治疗骨科中重度慢性疼痛的效果马利萍山东梁山县人民医院疼痛科,山东梁山272600[摘要]目的对骨科中重度慢性疼痛患者采用丁丙诺啡透皮贴剂治疗的效果进行探究。
方法选择2018年12月—2019年12月该院收治的骨科中重度疼痛患者86例作为该次研究对象,按照随机数表法将其划分为甲组和乙组,每组43例。
采用常规治疗方法对甲组进行治疗,采用丁丙诺啡透皮贴剂对乙组进行治疗。
对比两组患者的镇痛效果。
结果治疗1个月后,乙组的疼痛评分(3.6±0.4)分明显低于甲组(4.9±0.7)分,两组比较差异有统计学意义(t=10.574,P<0.05);在不良反应率方面,甲组达到了30.2%,乙组达到了7.0%。
丁丙诺啡-纳洛酮FDA说明书
__________________ ______________ _____________ ___________________ HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use BUNAVAIL safely and effectively. See full prescribing information for BUNAVAIL. BUNAVAIL (buprenorphine and naloxone) buccal film, CIII Initial U.S. Approval: 2002 INDICATIONS AND USAGEBUNAVAIL is a partial opioid agonist indicated for the maintenance treatment of opioid dependence. Prescription use of this product is limited under the Drug Addiction Treatment Act. (1) _______________DOSAGE AND ADMINISTRATION Apply BUNAVAIL buccal film as a single daily dose. (2) The recommended daily dose for maintenance is 8.4 mg/1.4 mg. DOSAGE FORMS AND STRENGTHS Buccal film: BUNAVAIL 2.1 mg buprenorphine/0.3 mg naloxone; BUNAVAIL 4.2 mg buprenorphine/0.7 mg naloxone and BUNAVAIL 6.3 mg buprenorphine/1 mg naloxone. (3) CONTRAINDICATIONS Hypersensitivity to buprenorphine or naloxone. (4) _______________ WARNINGS AND PRECAUTIONS _______________ •Buprenorphine can be abused in a similar manner to other opioids. Clinical monitoring appropriate to the patient’s level of stability is essential. Multiple refills should not be prescribed early in treatment or without appropriate patient follow-up visits. (5.1) • Significant respiratory depression and death have occurred in association with buprenorphine, particularly when taken by the intravenous (IV) route in combination with benzodiazepines or other CNS depressants (including alcohol). (5.2) • Consider dose reduction of CNS depressants, BUNAVAIL buccal film, or both in situations of concomitant prescription. (5.3) • Store BUNAVAIL buccal film safely and out of the sight and reach of children. Buprenorphine can cause severe, possibly fatal, respiratory depression in children. (5.4) • Chronic administration produces opioid-type physical dependence. Abrupt discontinuation or rapid dose taper may result in opioid withdrawal syndrome. (5.5) • Monitor liver function tests prior to initiation and during treatment and evaluate suspected hepatic events. (5.6) • Do not administer BUNAVAIL buccal film to patients with known hypersensitivity to buprenorphine or naloxone. (5.7) • An opioid withdrawal syndrome is likely to occur with parenteral misuse of BUNAVAIL buccal film by individuals physically dependent on full opioid agonists or by buccal administration before the agonist effects of other opioids have subsided. (5.8) • Neonatal withdrawal has been reported following use of buprenorphine by the mother during pregnancy. (5.9) • BUNAVAIL buccal film is not appropriate as an analgesic. There have been reported deaths of opioid naïve individuals who received a buprenorphine dose smaller than the lowest available BUNAVAIL strength. (5.10) • Buprenorphine/naloxone products are not recommended in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment (5.11) • Caution patients about the risk of driving or operating hazardous machinery. (5.12) ___________________ ADVERSE REACTIONS ___________________ Adverse events commonly observed with administration of BUNAVAIL buccal films during clinical trials are headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia and pain. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact (BioDelivery Sciences International) at 1-800-469-0261 or FDA at 1-800-FDA-1088 or /medwatch . ___________________ DRUG INTERACTIONS ____________________ • Monitor patients starting or ending CYP3A4 inhibitors or inducers for potential over or under dosing. (7.1) • Use caution in prescribing BUNAVAIL buccal film for patients receiving benzodiazepines or other CNS depressants and warn patients against concomitant self-administration/misuse. (7.3) USE IN SPECIFIC POPULATIONS • Pregnancy: Based on animal data, may cause fetal harm. (8.1) • Nursing mothers: Caution should be exercised when administered to a nursing woman. (8.3) • Safety and effectiveness of BUNAVAIL buccal film in patients below the age of 16 has not been established. (8.4) • Administer BUNAVAIL buccal film with caution to elderly or debilitated patients. (8.5) • Buprenorphine/naloxone products are not recommended in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment. (8.6) See 17 for PATIENT COUNSELING INFORMATION and Medication Guide 6/ 2014 FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 2.1 Maintenance 2.2 Method of Administration 2.3 Clinical Supervision 2.4 Patients With Hepatic Impairment 2.5 Unstable Patients 2.6 Stopping Treatment 2.7 Switching between SUBOXONE Sublingual Tablets or Films and BUNAVAIL buccal film 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Abuse Potential 5.2 Respiratory Depression 5.3 CNS Depression 5.4 Unintentional Pediatric Exposure 5.5 Dependence 5.6 Hepatitis, Hepatic Events 5.7 Allergic Reactions 5.8 Precipitation of Opioid Withdrawal Signs and Symptoms 5.9 Neonatal Withdrawal 5.10 Use in Opioid Naïve Patients 5.11 Use in Patients with Impaired Hepatic Function 5.12Impairment of Ability to Drive or Operate Machinery 5.13 Orthostatic Hypotension 5.14 Elevation of Cerebrospinal Fluid Pressure 5.15 Elevation of Intracholedochal Pressure 5.16 Effects in Acute Abdominal Conditions 5.17 General Precautions 6 ADVERSE REACTIONS 6.1 Adverse Events in Clinical Trials 7 DRUG INTERACTIONS 7.1 Cytochrome P-450 3A4 (CYP3A4) Inhibitors and Inducers 7.2 Antiretrovirals 7.3 Benzodiazepines 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.3Nursing Mothers 8.4Pediatric Use 8.5Geriatric Use8.6 Hepatic Impairment8.7 Renal Impairment9 DRUG ABUSE AND DEPENDENCE9.1 Controlled Substance9.2 Abuse9.3 Dependence10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment ofFertility16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION17.1 Safe Use17.2 Disposal of Unused*Sections or subsections omitted from the full prescribing information are not listed.FULL PRESCRIBING INFORMATION1 INDICATIONS AND USAGEBUNAVAIL buccal film is indicated for the maintenance treatment of opioid dependence and should be used as part of a complete treatment plan to include counseling and psychosocial support.Under the Drug Addiction Treatment Act (DATA) codified at 21 U.S.C. 823(g), prescription use of this product in the treatment of opioid dependence is limited to physicians who meet certain qualifying requirements, and who have notified the Secretary of Health and Human Services (HHS) of their intent to prescribe this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription.2 DOSAGE AND ADMINISTRATIONBUNAVAIL buccal film is applied to the buccal mucosa as a single daily dose. BUNAVAIL buccal film should be used in patients who have been initially inducted using buprenorphine sublingual tablets.The difference in bioavailability of BUNAVAIL compared to SUBOXONE sublingual tablet requires a different dosage strength to be administered to the patient. A BUNAVAIL 4.2/0.7 mg buccal film provides equivalent buprenorphine exposure to a SUBOXONE 8/2 mg sublingual tablet.Medication should be prescribed in consideration of the frequency of visits. Provision of multiple refills is not advised early in treatment or without appropriate patient follow-up visits.2.1 Maintenance• BUNAVAIL buccal film is indicated for maintenance treatment. The recommended target dosage of BUNAVAIL buccal film is 8.4/1.4 mg per day as a single daily dose.• The dosage of BUNAVAIL buccal film should be progressively adjusted in increments/decrements of 2.1/0.3 mg buprenorphine/naloxone to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms.• The maintenance dose of BUNAVAIL buccal film is generally in the range of 2.1/0.3 mg buprenorphine/naloxone to 12.6/2.1 mg buprenorphine/naloxone per day depending on the individual patient. Dosages higher than this have not been demonstrated to provide any clinical advantage.2.2 Method of AdministrationThe patient should:• use the tongue to wet the inside of the cheek or rinse the mouth with water to moisten the area immediately before placement of BUNAVAIL;• open the BUNAVAIL package immediately prior to use as indicated by the instructions; • hold the BUNAVAIL film with clean, dry fingers with the text (BN2, BN4, or BN6) facing up;• place the side of the BUNAVAIL film with the text (BN2, BN4, or BN6) against the inside of the cheek;• press and hold the film in place for 5 seconds.BUNAVAIL film(s) adhere to the moist buccal mucosa and should stay in place after this period. If multiple films need to be administered, the patient should immediately apply the next film according to the steps above. Note that when two films are required for one dose, the patient should place one film on the inside of one cheek and the other film on the inside of the other cheek. For doses requiring multiple films, no more than two films should be applied to the inside of one cheek at a time.BUNAVAIL film(s) completely dissolve after application. The patient should be instructed to avoid manipulating the film(s) with the tongue or finger(s) and avoid drinking or eating food until the film(s) dissolve. BUNAVAIL film should not be chewed or swallowed as this may result in lower peak concentrations and lower bioavailability [see Clinical Pharmacology (12.3)]. Instruct the patient to use the entire film. BUNAVAIL should not be cut or torn.Proper administration technique should be demonstrated to the patient.2.3 Clinical SupervisionTreatment should be initiated with supervised administration, progressing to unsupervised administration as the patient’s clinical stability permits. BUNAVAIL buccal film is subject to diversion and abuse. When determining the prescription quantity for unsupervised administration, consider the patient’s level of stability, the security of his or her home situation, and other factors likely to affect the ability to manage supplies of take-home medication. Ideally patients should be seen at reasonable intervals (e.g., at least weekly during the first month of treatment) based upon the individual circumstances of the patient. Medication should be prescribed in consideration of the frequency of visits. Provision of multiple refills is not advised early in treatment or without appropriate patient follow-up visits. Periodic assessment is necessary to determine compliance with the dosing regimen, effectiveness of the treatment plan, and overall patient progress.Once a stable dosage has been achieved and patient assessment (e.g., urine drug screening) does not indicate illicit drug use, less frequent follow-up visits may be appropriate. A once-monthly visit schedule may be reasonable for patients on a stable dosage of medication who are making progress toward their treatment objectives. Continuation or modification of pharmacotherapy should be based on the physician’s evaluation of treatment outcomes and objectives such as: 1. Absence of medication toxicity2. Absence of medical or behavioral adverse effects3. Responsible handling of medications by the patient4. Patient’s compliance with all elements of the treatment plan (including recovery-orientedactivities, psychotherapy, and/or other psychosocial modalities)5. Abstinence from illicit drug use (including problematic alcohol and/or benzodiazepine use) If treatment goals are not being achieved, the physician should re-evaluate the appropriateness of continuing the current treatment.2.4 Patients With Hepatic ImpairmentBecause the doses of this fixed combination product cannot be individually titrated, severe hepatic impairment results in a reduced clearance of naloxone to a much greater extent than buprenorphine, and moderate hepatic impairment also results in a reduced clearance of naloxone to a greater extent than buprenorphine, the combination product should generally be avoided in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment [see Warnings and Precautions (5.11)].2.5 Unstable PatientsPhysicians will need to decide when they cannot appropriately provide further management for particular patients. For example, some patients may be abusing or dependent on various drugs, or unresponsive to psychosocial intervention such that the physician does not feel that he/she has the expertise to manage the patient. In such cases, the physician may want to assess whether to refer the patient to a specialist or more intensive behavioral treatment environment. Decisions should be based on a treatment plan established and agreed upon with the patient at the beginning of treatment. Patients who continue to misuse, abuse, or divert buprenorphine products or other opioids should be provided with, or referred to, more intensive and structured treatment.2.6 Stopping TreatmentThe decision to discontinue therapy with BUNAVAIL buccal film after a period of maintenance should be made as part of a comprehensive treatment plan. Taper patients to avoid opioid withdrawal signs and symptoms.2.7 Switching between SUBOXONE Sublingual Tablets or Films andBUNAVAIL buccal filmThe difference in bioavailability of BUNAVAIL compared to SUBOXONE sublingual tablet requires a different dosage strength to be administered to the patient. A BUNAVAIL 4.2/0.7 mgbuccal film provides equivalent buprenorphine exposure to a SUBOXONE 8/2 mg sublingual tablet.Patients being switched between SUBOXONE dosage strengths and BUNAVAIL dosage strengths should be started on the corresponding dosage as defined below:Suboxone Sublingual Tablet Dosage Strength Corresponding BUNAVAIL Buccal FilmStrength4/1 mg buprenorphine/naloxone 2.1/0.3 mg buprenorphine/naloxone8/2 mg buprenorphine/naloxone 4.2/0.7 mg buprenorphine/naloxone12/3 mg buprenorphine/naloxone 6.3/1 mg buprenorphine/naloxone3 DOSAGE FORMS AND STRENGTHSBUNAVAIL buccal film is supplied as a yellow rectangular buccal film in three dosage strengths:•buprenorphine/naloxone 2.1 mg / 0.3 mg•buprenorphine/naloxone 4.2 mg / 0.7 mg•buprenorphine/naloxone 6.3 mg / 1 mg4 CONTRAINDICATIONSBUNAVAIL buccal film should not be administered to patients who have been shown to be hypersensitive to buprenorphine or naloxone as serious adverse reactions, including anaphylactic shock, have been reported [see Warnings and Precautions (5.7)].5 WARNINGS AND PRECAUTIONS5.1 Abuse PotentialBuprenorphine can be abused in a manner similar to other opioids, legal or illicit. Prescribe and dispense buprenorphine with appropriate precautions to minimize risk of misuse, abuse, or diversion, and ensure appropriate protection from theft, including in the home. Clinical monitoring appropriate to the patient’s level of stability is essential. Multiple refills should not be prescribed early in treatment or without appropriate patient follow-up visits [see Drug Abuse and Dependence (9.2)].5.2 Respiratory DepressionBuprenorphine, particularly when taken by the IV route, in combination with benzodiazepines or other CNS depressants (including alcohol), has been associated with significant respiratory depression and death. Many, but not all, post-marketing reports regarding coma and death associated with the concomitant use of buprenorphine and benzodiazepines involved misuse by self-injection. Deaths have also been reported in association with concomitant administration of buprenorphine with other depressants such as alcohol or other CNS depressant drugs. Patients should be warned of the potential danger of self-administration of benzodiazepines or other depressants while under treatment with BUNAVAIL buccal film [see Drug Interactions (7.3)]. In the case of overdose, the primary management should be the re-establishment of adequate ventilation with mechanical assistance of respiration, if required. Naloxone may be of value for the management of buprenorphine overdose. Higher than normal doses and repeated administration may be necessary.BUNAVAIL buccal film should be used with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression).5.3 CNS DepressionPatients receiving buprenorphine in the presence of opioid analgesics, general anesthetics, benzodiazepines, phenothiazines, other tranquilizers, sedative/hypnotics, or other CNS depressants (including alcohol) may exhibit increased CNS depression. Consider dose reduction of CNS depressants, BUNAVAIL buccal film, or both in situations of concomitant prescription [see Drug Interactions (7.3)].5.4 Unintentional Pediatric ExposureBuprenorphine can cause severe, possibly fatal, respiratory depression in children who are accidentally exposed to it. Store buprenorphine-containing medications safely out of the sight and reach of children and destroy any unused medication appropriately [see Patient Counseling Information (17.2)].5.5 DependenceBuprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. The withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset. Buprenorphine can be abused in a manner similar to other opioids. This should be considered when prescribing or dispensing buprenorphine in situations when the clinician is concerned about an increased risk of misuse, abuse, or diversion [see Drug Abuse and Dependence (9.3)].5.6 Hepatitis, Hepatic EventsCases of cytolytic hepatitis and hepatitis with jaundice have been observed in individuals receiving buprenorphine in clinical trials and through post-marketing adverse event reports. The spectrum of abnormalities ranges from transient asymptomatic elevations in hepatic transaminases to case reports of death, hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy. In many cases, the presence of pre-existing liver enzyme abnormalities, infection with hepatitis B or hepatitis C virus, concomitant usage of other potentially hepatotoxic drugs, and ongoing injecting drug use may have played a causative or contributory role. In other cases, insufficient data were available to determine the etiology of the abnormality. Withdrawal of buprenorphine has resulted in amelioration of acute hepatitis in some cases; however, in other cases no dose reduction was necessary. The possibility exists that buprenorphine had a causative or contributory role in the development of the hepatic abnormality in some cases. Liver function tests, prior to initiation of treatment is recommended to establish a baseline. Periodic monitoring of liver function during treatment is also recommended. A biological and etiological evaluation is recommended when a hepatic event is suspected. Depending on the case, BUNAVAIL buccal film may need to be carefully discontinued to prevent withdrawal signs and symptoms and a return by the patient to illicit drug use, and strict monitoring of the patient should be initiated.5.7 Allergic ReactionsCases of hypersensitivity to buprenorphine and naloxone containing products have been reported both in clinical trials and in the post-marketing experience. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported. The most common signs and symptoms include rashes, hives and pruritus. A history of hypersensitivity to buprenorphine or naloxone is a contraindication to the use of BUNAVAIL buccal film.5.8 Precipitation of Opioid Withdrawal Signs and SymptomsBecause it contains naloxone, BUNAVAIL buccal film is likely to produce withdrawal signs and symptoms if misused parenterally by individuals dependent on full opioid agonists such as heroin, morphine, or methadone. Because of the partial agonist properties of buprenorphine, BUNAVAIL buccal film may precipitate opioid withdrawal signs and symptoms in such persons if administered bucally before the agonist effects of the opioid have subsided.5.9 Neonatal WithdrawalNeonatal withdrawal has been reported in the infants of women treated with buprenorphine during pregnancy. From post-marketing reports, the time to onset of neonatal withdrawal signs ranged from Day 1 to Day 8 of life with most cases occurring on Day 1. Adverse events associated with the neonatal withdrawal syndrome included hypertonia, neonatal tremor,neonatal agitation, and myoclonus, and there have been reports of convulsions, apnea, respiratory depression, and bradycardia.5.10 Use in Opioid Naïve PatientsThere have been reported deaths of opioid naïve individuals who received a 2 mg dose of buprenorphine, smaller than the lowest strength of BUNAVAIL, for analgesia. BUNAVAIL buccal film is not appropriate as an analgesic.5.11 Use in Patients with Impaired Hepatic FunctionBuprenorphine/naloxone products are not recommended in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment. Because hepatic impairment results in a reduced clearance of naloxone to a much greater extent than buprenorphine, the doses of buprenorphine and naloxone in this fixed-dose combination product cannot be individually titrated. Therefore, patients with severe hepatic impairment will be exposed to substantially higher levels of naloxone than patients with normal hepatic function. This may result in an increased risk of precipitated withdrawal at the beginning of treatment (induction) and may interfere with buprenorphine’s efficacy throughout treatment. In patients with moderate hepatic impairment, the differential reduction of naloxone clearance compared to buprenorphine clearance is not as great as in subjects with severe hepatic impairment. Therefore, buprenorphine/naloxone products are not recommended for initiation of treatment (induction) in patients with moderate hepatic impairment due to the increased risk of precipitated withdrawal. However, buprenorphine/naloxone products may be used with caution for maintenance treatment in patients with moderate hepatic impairment who have initiated treatment on a buprenorphine product without naloxone. However, patients should be carefully monitored and consideration given to the possibility of naloxone interfering with buprenorphine’s efficacy [see Use in Specific Populations (8.6)].5.12 Impairment of Ability to Drive or Operate MachineryBUNAVAIL buccal film may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving a car or operating machinery, especially during treatment induction and dose adjustment. Patients should be cautioned about driving or operating hazardous machinery until they are reasonably certain that BUNAVAIL buccal film therapy does not adversely affect his or her ability to engage in such activities.5.13 Orthostatic HypotensionLike other opioids, BUNAVAIL buccal film may produce orthostatic hypotension in ambulatory patients.5.14 Elevation of Cerebrospinal Fluid PressureBuprenorphine, like other opioids, may elevate cerebrospinal fluid pressure and should be used with caution in patients with head injury, intracranial lesions, and other circumstances when cerebrospinal pressure may be increased. Buprenorphine can produce miosis and changes in the level of consciousness that may interfere with patient evaluation.5.15 Elevation of Intracholedochal PressureBuprenorphine has been shown to increase intracholedochal pressure, as do other opioids, and thus should be administered with caution to patients with dysfunction of the biliary tract.5.16 Effects in Acute Abdominal ConditionsAs with other opioids, buprenorphine may obscure the diagnosis or clinical course of patients with acute abdominal conditions.5.17 General PrecautionsBUNAVAIL buccal film should be administered with caution in debilitated patients and those with myxedema or hypothyroidism, adrenal cortical insufficiency (e.g., Addison’s disease); CNS depression or coma; toxic psychoses; prostatic hypertrophy or urethral stricture; acute alcoholism; delirium tremens; or kyphoscoliosis.6 ADVERSE REACTIONSBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.6.1 Adverse Events in Clinical TrialsThe safety of BUNAVAIL buccal film is supported by clinical trials using buprenorphine and naloxone sublingual tablets, and other trials using buprenorphine tablets and buprenorphine sublingual solutions, as well as an open-label study in 249 patients treated with BUNAVAIL buccal film. In total, safety data from clinical studies are available from over 3000 opioid-dependent subjects exposed to buprenorphine at doses in the range used in the treatment of opioid addiction. Few differences in the adverse event profile were noted among buprenorphine and naloxone sublingual tablets, buprenorphine sublingual tablets and a buprenorphine ethanolic sublingual solution.The safety and tolerability of BUNAVAIL was evaluated in a 12-week clinical study of BUNAVAIL in 249 opioid-dependent subjects stabilized on buprenorphine and naloxone sublingual tablet or film dosages of 8-32 mg/day.The following adverse reactions were reported to occur by at least 5% of patients in a 12-week study with BUNAVAIL: drug withdrawal syndrome, lethargy and headache.The adverse reactions listed below represent those that were reported by >1%, but less than 5% of patients from the 12-week clinical trial while receiving BUNAVAIL. Events are classified by system organ class.•General disorders and administration site conditions: fatigue and chills•Nervous system disorders: somnolence•Psychiatric disorders: drug dependence and insomnia•Gastrointestinal disorders: constipation and oral mucosal erythema•Respiratory, thoracic and mediastinal disorders: rhinorrhea•Skin and subcutaneous tissue disorders: hyperhidrosisThe following adverse events were reported to occur by at least 5% of patients in a 4-week study with buprenorphine and naloxone sublingual tablets (Table 1).Table 1Adverse Events (> 5%) by Body System and Treatment Group in a 4-week StudyBody System/ Adverse Event (COSTART) Terminology Buprenorphine/naloxone sublingualtablets 16/4 mg/day N=107n (%)PlaceboN=107n (%)Body as a WholeAsthenia 7 (6.5%) 7 (6.5%) Chills 8 (7.5%) 8 (7.5%) Headache 39 (36.4%) 24 (22.4%) Infection 6 (5.6%) 7 (6.5%) Pain 24 (22.4%) 20 (18.7%) Pain abdomen 12 (11.2%) 7 (6.5%) Pain back 4 (3.7%) 12 (11.2%) Withdrawal syndrome 27 (25.2%) 40 (37.4%) Cardiovascular SystemVasodilation 10 (9.3%) 7 (6.5%) Digestive SystemConstipation 13 (12.1%) 3 (2.8%) Diarrhea 4 (3.7%) 16 (15.0%) Nausea 16 (15.0%) 12 (11.2%) Vomiting 8 (7.5%) 5 (4.7%) Nervous SystemInsomnia 15 (14.0%) 17 (15.9%) Respiratory SystemRhinitis 5 (4.7%) 14 (13.1%)Skin and AppendagesSweating 15 (14.0%) 11 (10.3%)The adverse event profile of buprenorphine was also characterized in the dose-controlled study of buprenorphine solutions, over a range of doses in four months of treatment. Table 2 shows adverse events reported by at least 5% of subjects in any dose group in the dose-controlled study.Table 2Adverse Events (> 5%) by Body System and Treatment Group in a 16-week StudyBody System /Adverse Event (COSTART Terminology) Buprenorphine Dose*Very Low*(N=184)n (%)Low*(N=180)n (%)Moderate*(N=186)n (%)High*(N=181)n (%)Total*(N=731)n (%)Body as a WholeAbscess 9 (5%) 2 (1%) 3 (2%) 2 (1%) 16 (2%) Asthenia 26 (14%) 28 (16%) 26 (14%) 24 (13%) 104 (14%) Chills 11 (6%) 12 (7%) 9 (5%) 10 (6%) 42 (6%) Fever 7 (4%) 2 (1%) 2 (1%) 10 (6%) 21 (3%)Flu Syndrome 4 (2%) 13 (7%) 19 (10%) 8 (4%) 44 (6%) Headache 51 (28%) 62 (34%) 54 (29%) 53 (29%) 220 (30%) Infection 32 (17%) 39 (22%) 38 (20%) 40 (22%) 149 (20%) Injury Accidental 5 (3%) 10 (6%) 5 (3%) 5 (3%) 25 (3%) Pain 47 (26%) 37 (21%) 49 (26%) 44 (24%) 177 (24%) Pain Back 18 (10%) 29 (16%) 28 (15%) 27 (15%) 102 (14%) Withdrawal Syndrome 45 (24%) 40 (22%) 41 (22%) 36 (20%) 162 (22%) Digestive SystemConstipation 10 (5%) 23 (13%) 23 (12%) 26 (14%) 82 (11%) Diarrhea 19 (10%) 8 (4%) 9 (5%) 4 (2%) 40 (5%) Dyspepsia 6 (3%) 10 (6%) 4 (2%) 4 (2%) 24 (3%) Nausea 12 (7%) 22 (12%) 23 (12%) 18 (10%) 75 (10%) Vomiting 8 (4%) 6 (3%) 10 (5%) 14 (8%) 38 (5%) Nervous SystemAnxiety 22 (12%) 24 (13%) 20 (11%) 25 (14%) 91 (12%) Depression 24 (13%) 16 (9%) 25 (13%) 18 (10%) 83 (11%) Dizziness 4 (2%) 9 (5%) 7 (4%) 11 (6%) 31 (4%) Insomnia 42 (23%) 50 (28%) 43 (23%) 51 (28%) 186 (25%) Nervousness 12 (7%) 11 (6%) 10 (5%) 13 (7%) 46 (6%) Somnolence 5 (3%) 13 (7%) 9 (5%) 11 (6%) 38 (5%) Respiratory SystemCough Increase 5 (3%) 11 (6%) 6 (3%) 4 (2%) 26 (4%) Pharyngitis 6 (3%) 7 (4%) 6 (3%) 9 (5%) 28 (4%) Rhinitis 27 (15%) 16 (9%) 15 (8%) 21 (12%) 79 (11%) Skin and AppendagesSweat 23 (13%) 21 (12%) 20 (11%) 23 (13%) 87 (12%) Special SensesRunny Eyes 13 (7%) 9 (5%) 6 (3%) 6 (3%) 34 (5%)*Sublingual solution. Doses in this table cannot necessarily be delivered in film form, but for comparison purposes: “very low” dose (1 mg solution) would be less than a tablet dose of 2 mg; “low” dose (4 mg solution)。
丁丙诺啡透皮贴剂
在用药过量的情况下，如有必要，首先应重新建立一个维持-通畅的呼吸气道，用于协助或控制呼吸。采用其 他支持加措施（包括吸氧、给予血管升压类药物）以治疗循环性休克和肺水肿等症状，心脏骤停或心律失常将需 要给予加强型生命支持技术治疗。
纳洛酮对丁丙诺啡产生的呼吸抑制可能无任何逆转作用。在治疗丁丙诺啡用药过量期间，高剂量纳洛酮的极 限值是10～35mg/70kg，纳洛酮起效可能会延迟30分中或更长时间。还可以使用盐酸多沙普仑（一种呼吸兴奋 剂）。
注意事项：
滥用可能性
本品含丁丙诺啡，为μ阿片受体部分激动剂，属于国家特殊管理的精神药品。丁丙诺啡滥用形式与其他阿片 受体激动剂(合法或非法)相似，阿片受体激动剂是药物滥用者和药物成瘾者寻找对象，且易被非法倒卖。开具处 方或调剂本品时，如发现存在误用、滥用或倒卖风险增加情况，应考虑到上述风险。但是关于误用、滥用和倒卖 的担忧不应妨碍疼痛的合理治疗。
给患者开具处方前，需评估阿片类药物滥用或成瘾风险，本人或其家族有药物滥用史(包括药物或酒精滥用或 成瘾)或患有精神疾病的患者(如重度抑郁症)阿片类药物滥用风险会增加。风险增加的患者仍适合缓释阿片类药 物治疗;但是应加强对此类患者误用、滥用或成瘾体征的监察。由于此类药物即使在正确的临床应用中也具有成瘾 风险，因此所有接受阿片类药物治疗的患者均应常规监察误用、滥用和成瘾体征。
尚未开展丁丙诺啡与CYP3A4诱导剂的相互作用试验。丁丙诺啡透皮贴剂与酶诱导剂(如，苯巴比妥、卡马西 平、苯妥英、利福平)联合使用后，可能会导致清除率升高，继而降低药物的疗效。
某些全身性麻醉药(例如氟烷)及其他可诱导肝血流量下降的药品，可能会降低肝脏对丁丙诺啡的清除率。
药物过量：
临床症状
本品急性用药过量的临床表现为呼吸抑制、嗜睡发展成恍惚和昏迷、骨骼肌松弛、皮肤冰冷、瞳孔收缩、心 动过缓、低血压、部分或完全气道阻塞、非典型打鼾和死亡。在用药过量的情况下，由于严重缺氧，可能导致显 著的瞳孔散大，而非瞳孔缩小。
盐酸丁丙诺啡注射液
盐酸丁丙诺啡注射液【适用症】盐酸丁丙诺啡注射液为强效镇痛药，用于各类手术后疼痛、癌症疼痛、烧伤后疼痛、脉管炎引起的肢痛及心绞痛和其他内脏痛。
【注意事项】1．盐酸丁丙诺啡注射液有一定依赖性，戒断症状较轻，因此存在有滥用的可能，故按Ⅰ类精神药品管理，使用时应遵医嘱。
2．呼吸机能低下或紊乱者、已接受其它中枢神经抑制剂治疗者和高龄与虚弱者慎用。
3．盐酸丁丙诺啡注射液与受体亲和力高，常规剂量拮抗剂如纳洛酮，对已引起的呼吸抑制无用，推荐使用呼吸兴奋剂（如多沙普仑）。
【用法与用量】肌内注射，一次0.15―0.3mg,可每隔6―8小时或按需注射。
疗效不佳时可适当增加用量。
【禁忌症】对盐酸丁丙诺啡注射液有过敏史、重症肝损伤、脑部损害、意识模糊及颅内压升高患者禁用。
六岁以下儿童、孕妇哺乳期妇女以及轻微疼痛或疼痛原因不明者不宜使用。
【儿童用药注意事项】六岁以下儿童不宜使用。
【孕妇、哺乳期妇女用药注意事项】动物实验有难产、哺乳困难和胎儿生存率低等报导，药物可经乳汁分泌，故孕妇及哺乳期妇女不宜使用。
【不良反应】头晕、嗜睡、恶心呕吐、出汗、头痛、皮疹。
【药物相互作用】盐酸丁丙诺啡注射液如与另一种阿片受体激动剂合用，可引起这些药物的戒断症状。
与单胺氧化酶抑制剂有协同作用。
【药理】盐酸丁丙诺啡注射液为镇痛药，为阿片受体的部分拮抗―激动剂，动物实验表明对小鼠镇痛作用明显，文献报道，盐酸丁丙诺啡注射液对无依赖性犬能抑制屈肌和皮肤的抽搐反射、抑制咳嗽反射、减慢心率、降低收缩压，对心血管参数无明显影响。
盐酸丁丙诺啡注射液能产生吗啡样的呼吸抑制、起始慢，持续时间长，尚未见严重呼吸抑制的报道。
对大鼠的慢性毒性研究表明，盐酸丁丙诺啡注射液对重要器官未发现明显毒性作用，无致突变作用和生殖毒性。
动物依赖性实验表明，盐酸丁丙诺啡注射液身体依赖性低于吗啡和度冷丁，而精神依赖性潜力与吗啡相当。
临床研究表明，盐酸丁丙诺啡注射液具有较强的镇痛作用，其镇痛效果优于度冷丁。
丁丙诺菲透皮贴联合普瑞巴林治疗老年带状疱疹后神经痛的临床观察
丁丙诺菲透皮贴联合普瑞巴林治疗老年带状疱疹后神经痛的临床观察何颖;万成福;宋涛【摘要】目的：观察丁丙诺菲透皮贴联合普瑞巴林治疗老年带状疱疹后神经痛的临床效果。
方法60例老年带状疱疹后神经痛患者随机分为试验组和对照组。
试验组：丁丙诺菲透皮贴联合普瑞巴林；对照组：单独应用口服普瑞巴林。
治疗8周后记录两组患者用药前、用药后2周、4周、8周的疼痛评分（visual analogue scale，VAS）、睡眠评分、普瑞巴林日剂量及不良反应发生率。
结果两组患者治疗后VAS评分明显低于治疗前(P<0.01)，治疗后4周及8周试验组VAS评分明显低于对照组(P<0.05)；用药治疗后两组患者睡眠质量明显改善(P<0.05)；联合应用丁丙诺菲透皮贴后可明显减少试验组普瑞巴林的用量(P<0.05)；联合应用丁丙诺菲透皮贴可以显著减少普瑞巴林相关不良反应头晕、嗜睡的发生率(P<0.05)。
结论丁丙诺菲透皮贴联合普瑞巴林对老年带状疱疹后神经痛患者的临床效果优于单独应用普瑞巴林，不良反应较小。
%ObjectiveTo observed the effect of buprenorphine transdermal patches combined with pregabalin in gerontic patients with PHN.Methods60 patients were divided into experimental group and control group randomly. Patients of experimental group were treated with buprenorphine transdermal patches combined with pregabalin. The control group were orally administered pregabalin simply. The pain scores (VAS scores), sleep scores, doses of pregabalin and adverse reactions at each time point were recorded.ResultsThere were a signiifcant decline in VAS scores and sleep scores after treatment in 2 groups(P<0.01). Compared with the control group, the VAS scores and thedose of pregabalin were signiifcantly lower at 4, 8 weeks after treatment(P<0.05). The incidence of dizzy and drowsiness were higher in control group(P<0.05), but there were no signiifcant difference in the incidence of other side effects.ConclusionThe combination of buprenorphine transdermal patches and pregabalin is effective and safe for the gerontic patients with PHN.【期刊名称】《中国医药指南》【年(卷),期】2015(000)021【总页数】2页(P1-2)【关键词】带状疱疹后神经痛;丁丙诺菲透皮贴;普瑞巴林【作者】何颖;万成福;宋涛【作者单位】辽宁省铁岭市妇婴医院麻醉科，辽宁铁岭 112000;中国医科大学附属第一医院疼痛科，辽宁沈阳 110001;中国医科大学附属第一医院疼痛科，辽宁沈阳 110001【正文语种】中文【中图分类】R752.1+2带状疱疹后神经痛（postherpetic neuralgia，PHN）是水痘带状疱疹病毒感染后累及周围神经导致的一种神经病理性疼痛综合征[1-2]，表现为针刺样痛或者电击样疼痛，伴有触觉过敏、痛觉超敏等症状，好发于老年和免疫功能低下患者[3]，是临床上难治性疾病之一。
- 1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。
丁丙诺啡透皮贴剂说明书
卢郁琴
【药品名称】
通用名称：丁丙诺啡透皮
英文名称：Buprenorphine Transdremal Patches
汉语拼音：Dingbingnuofei Toupitieji
【性状】
本品为圆角具有铝制保护衬垫的浅褐色贴剂，中央为药物贮库，背面印有蓝色品名、规格及释放速率字样。
5mg本品为正方形、圆形边角的浅褐色透皮贴剂。
标有‘Norspan5μg/h’。
10mg:本品为长方形、圆形边角的浅褐色透皮贴剂。
标有‘Norspan10μg/h’。
20m本品为正方形、圆形边角的浅褐色透皮贴剂。
标有‘Norspan20μg/h’g:。
适应症
用于非阿片类止痛剂不能控制的慢性疼痛。
【规格】
（1）5mg（6.25cm²）。
额定释放速率：每小时5微克丁丙诺啡（时间总共为7天）。
（2）10mg（12.5cm²）。
额定释放速率：每小时10微克丁丙诺啡（时间总共为7天）。
（3）20mg（25cm²）
额定释放速率：每小时20微克丁丙诺啡（时间总共为7天）。
用法用量
丁丙诺啡透皮贴剂每贴使用7天。
丁丙诺啡透皮贴剂不适用于治疗急性疼痛。
十八岁以上患者：
初始剂量应为最低的丁丙诺啡透皮贴剂剂量（5μg/h的丁丙诺啡透皮贴剂）。
应考虑患者先前的阿片类药物的用药史，以及患者当前的一般情况和疾病情况。
剂量调整：
在开始使用丁丙诺啡透皮贴剂治疗和剂量调整期间，患者应使用通常推荐剂量的短效补充止痛药，直到达到丁丙诺啡透皮贴剂的止痛效果。
在所有剂量达到最大的有效性之前3天，不能增加剂量。
随后的剂量增加应以对补充性止痛药的需求和患者对贴剂的止痛效果的反应为基础。
增加剂量时，可更换为尺寸较大的贴剂，或者在不同的部位联合使用另一贴剂以达到理想的剂量。
建议无论何种剂量的丁丙诺啡透皮贴剂，每次最多同时使用两贴。
在随后的3-4周不要在相同的部位使用新的贴剂。
使用部位:
丁丙诺啡透皮贴剂应使用于上臂外侧、前胸上部、后背上部或胸部侧方没有过敏的完好皮肤，请不要使用于任何有较大疤痕的皮肤部位。
丁丙诺啡透皮贴剂应使用于毛发较少或没有毛发的皮肤部位。
如果无法做到，应使用剪刀将毛发剪去，但不要使用剃须刀剃除毛发。
如果使用部位必须进行清洁，只可用清水进行清洗。
不得使用肥皂、酒精、油、洗液或擦洗设备。
在使用贴剂之前皮肤必须干燥。
在打开封条之后，必须立即使用。
在移去保护层之后，应用手掌将透皮贴剂紧压约30分钟，以确保完全接触，特别是边缘部位。
如果贴剂的边缘脱落，应在相应的位置用胶带粘贴。
贴剂应连续使用7天。
盆浴、淋浴、或游泳都不影响贴剂使用，如果贴剂脱落，应使用一个新的贴剂。
使用时间：
任何情况下使用丁丙诺啡透皮贴剂不应超过其必要治疗时间。
如果根据病情和严重程度有必要长期应用丁丙诺啡透皮贴剂时，须对患者进行仔细、定期的监测（如有必要，可间歇性治疗）以确定患者是否有必要继续使用。
停药：
在去除丁丙诺啡透皮贴剂之后，丁丙诺啡的血清药物浓度逐渐降低，因此止痛作用尚可维持一定时间。
丁丙诺啡透皮贴剂治疗后接着使用其他的阿片类药物时应考虑到这点。
一般原则下，在去除丁丙诺啡透皮贴剂24小时内不应使用其他的阿片类药物。
目前有关的停止使用去除贴剂后使用其他阿片类药物治疗起始剂量的资料有限。
【不良反应】
已观察到下述不良反应：
免疫系统：
不常见：高血压。
代谢和营养：
不常见：脱水。
神经系统：
很常见：头痛、头晕、嗜睡。
眼部：
罕见：干眼、视线模糊。
耳和迷路：
不常见：耳鸣、眩晕。
心脏：
不常见：心绞痛、心悸、心动过速。
呼吸、胸、纵隔：
常见：呼吸困难。
【禁忌】
丁丙诺啡透皮贴剂在下列情况下禁用：
-已知对活性成份丁丙诺啡或任何其他辅料过敏的患者；
-阿片类药物依赖的患者和麻醉药的替代治疗；
-呼吸中枢和功能严重受损或者可能出现这种情况的患者；
-对正在使用单胺氧化酶抑制剂或在前两周内使用过单胺氧化酶抑制剂的患者；
-肌无力的患者；
-震颤性谵妄的患者。
【注意事项】
滥用可能性
本品含丁丙诺啡，为μ阿片受体部分激动剂，属于国家特殊管理的精神药品。
丁丙诺啡滥用形式与其他阿片受体激动剂（合法或非法）相似，阿片受体激动剂是药物滥用者和药物成瘾者寻找对象，且易被非法倒卖。
开具处方或调剂本品时，如发现存在误用、滥用或倒卖风险增加情况，应考虑到上述风险。
但是关于误用、滥用和倒卖的担忧不应妨碍疼痛的合理治疗。