Instructions for Penciclovir for Injection
Release time:
2020-07-31
核准日期:2007年8月31日
第1次修改日期:2008年 05月28日
第2次修改日期:2014年 10月31日
恒奥普康
注射用喷昔洛韦说明书
请仔细阅读说明书并在医师指导下使用
【药品名称】
通用名称:注射用喷昔洛韦
商品名称:恒奥普康
英文名称:Penciclovir for Injection
汉语拼音:Zhusheyong Penxiluowei
【成份】
本品主要成份为喷昔洛韦,辅料为低分子右旋糖酐和氢氧化钠。
化学名称:9-[4-羟基-3-(羟甲基)-丁基]鸟嘌呤。
化学结构式:

分子式:C10H15N5O3
分子量:253.26
【性状】
本品为白色疏松块状物或粉末。
【适应症】
适用于严重带状疱疹患者,如出血性带状疱疹,坏疽性带状疱疹,播散性带状疱疹,三叉神经支带状疱疹,带状疱疹脑膜炎,严重疼痛的早期带状疱疹等和免疫机能障碍并发的带状疱疹。
【规格】0.25g。
【用法用量】
一次每公斤体重5mg,一日2次,隔12小时滴注一次,每次滴注时间应持续1小时以上,5-7日为一疗程。
临用前,取本品1瓶(含喷昔洛韦0.25g),用适量灭菌注射用水或氯化钠注射液使之溶解,再用氯化钠注射液至少100ml稀释,供静脉滴注用。
有肾脏疾病、脱水或同时使用其它对肾脏有毒性药物的病人,应调整剂量,缓慢静脉滴注(1小时以上)。
【不良反应】
1、静脉用药在注射部位可发生静脉炎和局部刺激,这是注射液pH值高(大于9.0)的缘故,而非喷昔洛韦的直接效应。
2、喷昔洛韦浓度过高可导致肾小管和集合管损害,并引起血肌酐值升高和肾功能损害,可引起肾区疼痛,这常发生于快速静脉滴注。
3、临床试验中曾见胃肠道反应、尿中红细胞高于正常值、头痛、头晕、双下肢及内踝水肿、手足发热、鼻塞、腹泻和寒战等。
【禁忌】
对本品有过敏反应史者禁用,肾功能异常者、儿童及孕妇慎用。
【注意事项】
1、对更昔洛韦过敏者也可能对本品过敏。
2、本品为静脉滴注用药,忌用作其它途径给药。
3、静脉滴注时应缓慢(1小时以上),防止局部浓度过高,引起疼痛及炎症。
4、溶液配制后应立即使用,不能冷藏,因冷藏时会析出结晶,用剩溶液应废弃,稀释药液时出现白色浑浊或结晶则不能使用。
5、本品呈碱性,与其它药物混合时易引起溶液pH值改变,应尽量避免配伍使用。
6、有肾脏疾病、脱水或同时使用其它对肾脏有毒性药物的病人,应调整剂量,缓慢静脉滴注(1小时以上)。
【孕妇及哺乳期妇女用药】
药物能通过胎盘,虽动物实验证实对胚胎无影响,但孕妇用药仍需权衡利弊。
药物在乳汁中的浓度为血药浓度的0.6~4.1倍,虽未发现婴儿异常,但哺乳期妇女应慎用。
【儿童用药】
儿童中虽未发现特殊不良反应,但应慎用。新生儿不宜以含苯甲醇的稀释液配制滴注液,否则易引起致命性的综合征,包括酸中毒、中枢抑制、呼吸困难、肾功能衰竭、低血压、癫痫和颅内出血等。
【老年用药】
由于生理性肾功能的衰退,应用本品需注意调整剂量。
【药物相互作用】
1.与干扰素或甲氨蝶呤(鞘内)合用,可能引起精神异常,应慎用。
2.与肾毒性药物合用可加重肾毒性,特别是肾功能不全者更易发生。
3.与齐多夫定(Zidovudine)合用可引起肾毒性,表现为深度昏睡和疲劳。
4.与丙磺舒竞争性抑制有机酸分泌,合并用丙磺舒可使本品的排泄减慢,半衰期延长,体内药物蓄积。
【药物过量】尚不明确。
【临床试验】
本项临床试验采用多中心、随机双盲、阳性药对照的方法评价注射用喷昔洛韦治疗严重带状疱疹的疗效和安全性。对于带状疱疹患者,给予注射用喷昔洛韦粉针剂每次0.25g(1瓶),临用前将药物加适量注射用水或氯化钠注射液使之溶解,再加入到250ml氯化钠注射液中,供静脉滴注。每日两次,每8~12小时静脉滴注1次。用药疗程:7天。总观察时间为21天(必要时需随访至第28天)。患者于用药后第1~7,8,14,21天,(必要时增加第28天)接受观察,对时间指标:开始结痂时间、全部结痂时间、开始脱痂时间、全部脱痂时间,以及疼痛开始减轻时间、疼痛完全消失时间、新水疱停止出现时间、水疱完全消退时间;主观指标:有无后遗神经痛及后遗神经痛的持续时间;客观指标:包括丘疱疹/水疱、血疱、坏死、糜烂、红斑/水肿、皮损分布范围三方面进行疗效评价。
Ⅱ期109例带状疱疹临床试验结果表明:注射用喷昔洛韦治疗带状疱疹,水疱停止出现时间1.44±1.21天,水疱消退时间4.53±3.29天,开始结痂时间2.85±1.74天,全部结痂时间6.07±3.35,开始脱痂时间7.24±3.51天,全部脱痂时间13.72±5.14,疼痛减轻时间3.22±3.32天,疼痛消失时间11.82±8.63天。
对于后遗神经痛的发生率,注射用喷昔洛韦组为2.75%。对于客观指标治疗7天、14天、28天的总有效率分别为80.74%、、97.25%、100%。对于疼痛指标,
治疗7天、14天、28天的总有效率分别为66.35%、85.04%、98.13%。
Ⅲ期345例带状疱疹临床试验结果表明:
注射用喷昔洛韦治疗带状疱疹,水疱停止出现时间为1.08±1.13天,水疱消退时间为2.52±1.31天,开始结痂时间为2.92±1.56天,全部结痂时间为5.98±2.87天,开始脱痂时间为6.42±2.72天,全部脱痂时间为12.65±4.42天,疼痛减轻时间为3.34±2.63天,疼痛消失时间为11.56±6.26天。
对于后遗神经痛的发生率,注射用喷昔洛韦组为8.3%。
在有效率方面,第4、8、14、21天时,注射用喷昔洛韦组的有效率分别为18.2%、69.6%、96.4%和99.1%。
25例严重带状疱疹患者,如出血性带状疱疹,坏疽性带状疱疹,播散性带状疱疹,三叉神经支带状疱疹,带状疱疹脑膜炎、严重疼痛的早期带状疱疹等和免疫机能障碍并发的带状疱疹补充临床试验结果表明:
注射用喷昔洛韦治疗带状疱疹,水疱停止出现时间为1.42±0.83天,水疱消退时间为5.88±3.53天,开始结痂时间为2.33±1.13天,全部结痂时间为5.65±2.21天,开始脱痂时间为7.17±4.32天,全部脱痂时间为14.83±5.73天,疼痛开始减轻时间为2.33±1.37天,疼痛消失时间为12.90±5.86天。
对于后遗神经痛的发生率,注射用喷昔洛韦组为33.3%。
在有效率方面,第4、8、14、21天时,注射用喷昔洛韦组的有效率分别为32.0%、84.0%、88.0%和96.0%。
在安全性方面,通过对患者的询问、观察及在用药前后进行血常规(白细胞、红细胞、血红蛋白、血小板),尿常规(尿蛋白、红细胞、白细胞、尿糖、酮体),肝功能(ALT、AST),肾功能(BUN、CREA),心电图的化验结果来发现不良事件,进行安全性评价:
通过对Ⅱ期临床试验109例,Ⅲ期临床试验345例及补充临床试验25例患者应用该药后的观察,无严重不良事件发生。经医生判断,与本药物相关的不良事件偶见:注射部位疼痛、恶心、呕吐、头痛、头晕、鼻塞、手足发热、寒战、静脉炎、腹泻、大便次数增多、双下肢及内踝水肿。经实验室检查分析,用药后血常规化验中有3例白细胞低于4.0×109/L、2例红细胞低于4.0×1012/L且血红蛋白低于130g/L,1例血小板低于100×109/L。用药后的尿常规化验中,有4例白细胞高于正常值,有3例红细胞高高于正常值。心电图检查中有3例用药前正常,用药后心电图出现心率不齐,心电图医师认为无临床意义。
【药理毒理】
药理作用
本品为核苷类抗病毒药,体外对Ι型和П型单纯性疱疹病毒有抑制作用。在病毒感染的细胞中,病毒胸腺嘧啶脱氧核苷激酶将本品磷酸化为喷昔洛韦单磷酸盐,然后细胞激酶将喷昔洛韦单磷酸盐转化为喷昔洛韦三磷酸盐。体外实验表明,喷昔洛韦三磷酸盐与脱氧鸟嘌呤核苷三磷酸盐竞争性抑制单纯疱疹病毒多聚酶,从而选择性抑制单纯疱疹病毒DNA 的合成和复制。
耐本品的单纯疱疹病毒突变株的产生是由于病毒胸腺嘧啶脱氧核苷激酶或DNA多聚酶性质发生了改变,最常见耐阿昔洛韦的病毒突变株缺乏胸腺嘧啶核苷激酶,它们对本品也耐药。
毒理研究
某些动物试验显示高浓度的喷昔洛韦可致突变,但无染色体改变的依据。在对细胞无害的浓度下喷昔洛韦未表现出致突变作用。
大鼠和兔静脉注射喷昔洛韦的I~Ш段生殖毒性试验中,大鼠最高剂量为80mg/kg/d,兔为50mg/kg/d,结果表明喷昔洛韦对受试动物的胚胎发育和生活能力、多代发育、生殖能力及生殖行为等仅有轻微或没有影响。长期大剂量注射可致动物睾丸萎缩和精子数减少,停药可部分恢复。
动物实验未见致癌依据。
【药代动力学】
10名受试者单次静脉滴注喷昔洛韦后,血浆浓度-时间曲线经WinNonLin程序采用非房室模型进行拟和计算,消除速率常数ke为0.3680 ±0.04891/hr,消除半衰期t1/2为1.91 ±0.26 hr,达峰时间Tmax为1.00 ±0.00 hr,达峰浓度Cmax为9.7745 ±1.5866 mg/L,药时曲线下面积AUC0-t为19.106 ±2.853 hr*mg/L,药时曲线下面积AUC0-∞为19.619 ±2.868 hr*mg/L,表观分布容积Vd为1.451 ±0.382 L/kg,表观清除率CL为0.520 ±0.079 L/hr/kg。
文献报道滴注相同剂量后主要药代动力学参数:消除半衰期t1/2为1.90 ±0.25 hr,达峰时间Tmax为0.95 ±0.1 hr,达峰浓度Cmax为12.1 ±3.1 mg/L,
药时曲线下面积AUC0-∞为21.1 ±3.4 hr*mg/L。本研究结果与文献报道基本一致。
文献报道滴注相同剂量后表观分布容积V为102 ±20 L,表观清除率CL为37.6 ±9.5 L/hr。经体重校正后进行对比,本研究结果与文献报道基本一致。
10 名受试者单次静脉滴注喷昔洛韦后,约50%的喷昔洛韦在给药后2小时经尿排出,10小时后排出量很少,12小时尿喷昔洛韦累积排出率为68.8±11.9%。
文献报道滴注相同剂量后72小时尿喷昔洛韦累积排出率为73.1±5.8%。因此,喷昔洛韦主要经肾排泄,本研究结果与文献报道基本一致。
表6.1 主要药代动力学参数对比表
|
参数 |
试验测定结果 |
文献数值 |
|
剂量 |
10 mg•kg-1 |
10 mg•kg-1 |
|
t1/2 |
1.91 ±0.26 hr |
1.90 ±0.25 hr |
|
Tmax |
1.00 ±0.00 hr |
0.95 ±0.1 hr |
|
Cmax |
9.775 ±1.587 mg/L |
12.1 ±3.1 mg/L |
|
AUC0-t |
19.106 ±2.853 hr*mg/L |
21.1 ±3.4 hr*mg/L |
|
Vd |
1.451 ±0.382 L/kg |
102 ±20 L |
|
CL |
0.520 ±0.079 L/hr/kg |
37.6 ±9.5 L/hr |
|
12小时尿累积排出率 |
68.8±11.9% |
- |
|
72小时尿累积排出率 |
- |
73.1±5.8% |
据文献报道,药物能通过胎盘,虽动物实验证实对胚胎无影响,但孕妇用药仍需权衡利弊。药物在乳汁中的浓度为血药浓度的0.6~4.1倍,虽未发现婴儿异常,但哺乳期妇女应慎用。
【贮藏】遮光,密闭,在阴凉处(不超过20℃)保存。
【包装】管制抗生素瓶装,1瓶/盒。
【有效期】暂定24个月。
【执行标准】YBH02122007
【批准文号】国药准字H20070186
【生产单位】
企业名称:浙江尖峰药业有限公司
地 址:浙江省金华市婺城区白汤下线高畈段58号
电 话:0579-82661998(咨询) 0579-82131973(销售)
传 真:0579-82661998
邮 编:321075
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07-31
Peak International Trade Won Cotton Yarn Delivery Warehouse Qualification
On August 2, Zhengzhou Commodity Exchange issued "on the establishment of a new designated cotton yarn delivery warehouse and the announcement of the water", the peak international trading company officially obtained the Zheng Shang designated delivery warehouse qualification. According to the amendment to the cotton yarn futures business rules announced by Zheng Shang in March, the social warehouse delivery method will be introduced on the basis of retaining the original factory warehouse delivery, and will take the lead in implementing it in Shandong, Henan, Jiangsu and Zhejiang. As one of the eight new warehouse delivery units after the amendment is issued, Jianfeng International Trade can carry out cotton yarn futures delivery business from September 2019. Lanxi City, a subsidiary of Jinhua, is a "famous weaving city in China" and a national textile industry base. It has more than 1000 textile enterprises and an annual demand for cotton yarn of more than 1 million tons. After Jianfeng International Trade obtains the qualification for cotton yarn futures delivery, it can not only provide cotton yarn futures delivery sites for Lanxi cotton textile industry and upstream and downstream merchants, but also effectively serve Jinhua counties and cities, Xiaoshan, Shaoxing, Quzhou, Wenzhou and other places, and other provinces, and Fujian provinces. Since Jianfeng International Trade became a futures delivery warehouse in 2009, it has carried out four types of business of Dalian Commodity Exchange PVC, PE, PP and plywood. Cotton yarn delivery is the company's first business variety in Zhengzhou Commodity Exchange. At present, Jianfeng International Trade is actively organizing learning and training on cotton yarn business knowledge, actively expanding business channels, and understanding the actual needs of upstream and downstream industries to ensure the operation, service quality and delivery efficiency of this new business. (Huang Zhiyu)
2020
07-22
Peak Pharmaceuticals Ranked "Top 100 Chinese Drugs"
From July 15 to 18, the National Pharmacy Week and China Pharmaceutical Innovation and Development Conference was held in Jinan, Shandong Province. The conference released the "2018 China Pharmaceutical Industry Top 100 Series List". Zhejiang Jianfeng Pharmaceutical Co., Ltd. ranked 74th in the "TOP100 List of Chinese Pharmaceutical Enterprises. The "2018 Top 100 Series List of Chinese Pharmaceutical Industry" is divided into five sub-lists: "TOP100 List of Chinese Pharmaceutical Enterprises", "TOP100 List of Chinese Traditional Medicine Enterprises", "TOP20 List of Chinese CRO (including CDMO) Enterprises", "TOP20 List of Chinese Medical Devices (including IVD) Enterprises" and "TOP20 List of Chinese Biomedicine (including Blood Products, Vaccines, Insulin, etc.) Enterprises. The "chemical pharmaceutical enterprise" in the "TOP100 list of Chinese pharmaceutical enterprises" refers to the enterprises whose terminal sales of chemical drugs account for more than 51% of the total terminal income of the enterprises. The selection score consists of two parts, one is the innovation driving force of the enterprise, that is, the R & D comprehensive index score of R & D investment in 2018, accounting for 40% of the weight; The second is the professional promotion power of the enterprise, that is, the terminal quantitative data determined by the final selection needs of clinicians and patients in 2018, accounting for 60% of the weight; the objects participating in the selection are pharmaceutical industry enterprises registered in China (excluding subsidiaries of multinational pharmaceutical enterprises in China) and whose main business is pharmaceutical manufacturing. The convening of the conference and the release of the list have received widespread attention from the industry. Relevant leaders of the state and Shandong Province attended the meeting, chief scientist of Peak Pharmaceutical, Chinese Academy of Engineering
2020
07-31