英文药名：Tygacil Injection（Tigecycline）

中文药名：替格环素注射剂

生产厂家：辉瑞公司日本
药品介绍：
药品英文名
Tigecycline
药品别名
Tygacil，替格环素，老虎霉素
药物剂型
注射剂：50mg。
药理作用
本品是甘氨酰环素(Glycylcyclines)类抗菌药，能与30S核糖体亚单位结合，阻止氨酰tRNA分子进入核糖体的A位，从而抑制细菌蛋白质的翻译，并阻止氨基酸残基进入肽链。本品具有广谱抗菌活性，对多种耐药菌有效。抗菌谱如下。革兰阳性菌：粪肠球菌(万古霉素敏感菌)、金黄色葡萄球菌(甲氧西林敏感的或耐药菌)、无乳链球菌、咽峡炎链球菌、化脓性链球菌。革兰阴性菌：弗罗因德枸橼酸杆菌、阴沟肠杆菌、大肠埃希菌、奥克西托克雷白杆菌、肺炎克雷伯杆菌。厌氧菌：脆弱拟杆菌、多形拟杆菌、单形拟杆菌、普通拟杆菌、产气荚膜梭状芽孢杆菌、微小消化链球菌。
药动学
单次静脉滴注本品100mg及多剂量给药(每12h给予本品50mg)后主要药代动力学参数如下：峰浓度(Cmax)分别为0.90～1.45μg/ml和0.63～0.87μg/ml；药时曲线下面积(AUC)分别为5.19μg·h/ml和4.70μg·h/ml；半衰期(t1/2)分别为27.1h和42.4h，清除率(CL)分别为21.8L/h和23.8L/h；稳态分布容积(Vss)分别为568L和639L。本品血浆蛋白结合率为71%～89%，稳态分布容积大，显示本品可分布到组织中。连续静脉滴注本品后，本品在肺泡中的药量是血液中药量的78倍，上皮细胞衬液中的药量比血浆中的药量高32%。单剂量静注本品4h后，胆囊、肺部、结肠中药物浓度分别是血浆药物浓度的38倍、8.6倍和2.1倍，而在滑囊液和骨组织中的药物浓度较低。本品代谢较少，主要以原形药物和少量代谢物形式经胆汁分泌后随粪便排泄和经尿液排出体外。肝功能不全患者排泄减慢。
适应证
本品主要用于治疗18岁以上患者由敏感菌引起的感染。
1.大肠埃希菌、金黄色葡萄球菌(甲氧西林敏感的或耐药菌)、无乳链球菌、咽峡炎链球菌、化脓性链球菌、脆弱拟杆菌引起的复杂性皮肤及皮肤结构感染。
2.弗罗因德枸橼酸杆菌、阴沟肠杆菌、大肠埃希杆菌、奥克西托克雷白杆菌、肺炎克雷伯杆菌、万古霉素敏感的粪肠球菌、甲氧西林敏感的金黄色葡萄球菌、咽峡炎链球菌、脆弱拟杆菌、多形拟杆菌、单形拟杆菌、普通拟杆菌、产气荚膜梭状芽孢杆菌、微小消化链球菌引起的复杂腹腔内感染。
禁忌证
1.对本品过敏者禁用。
2.生殖毒性分级为D，孕妇不推荐使用。
3.18岁以下儿童不推荐使用。
4.牙齿发育期使用本品可引起永久性牙齿变色，怀孕后期、婴儿及8岁以下儿童应避免使用，除非其他药物无效。
注意事项
1.本品可引起不同程度的假膜性肠炎甚至危及生命，用药后出现腹泻的患者应注意临床鉴别诊断。
2.本品可改变肠道正常菌群，引起梭状芽孢杆菌的过度繁殖，诱发抗生素相关性结肠炎。轻者停用本品，中度和重度者应考虑液体、电解质及蛋白质支持治疗。
3.本品大剂量使用可致恶心、呕吐，本品不易通过透析消除。
4．20～25℃保存。溶解好的输液室温保存不超过6h，2～8℃可保存24h。
不良反应
1.全身：腹痛、脓肿、无力、头痛、背痛、发热、寒战、感染、疼痛、败血症性休克、变态反应。
2.心血管系统：高血压、低血压、静脉炎、血栓性静脉炎、心动过缓、心动过速、血管舒张。
3.消化系统：恶心、呕吐，食欲减退、消化不良、便秘、腹泻、口干、黄疸。
4.血液及淋巴系统：贫血、白细胞增多、血小板增多、血小板减少、活化部分凝血激酶时间延长、凝血酶原时间延长、嗜曙红细胞增多、国际标准化比值增加。
5.代谢及营养：碱性磷酸酶升高、淀粉酶升高、血尿素氮升高、肌酐升高、乳酸脱氢酶升高、丙氨酸转移酶升高、天冬氨酸转移酶升高、外周水肿、低血糖、高血糖、胆红素血症、低钾血症、低蛋白血症、低钙血症、低钠血症。
6.神经系统：眩晕、失眠、瞌睡、味觉颠倒。
7.呼吸系统：咳嗽加剧、呼吸困难。
8.皮肤及附属：瘙痒、药疹、出汗。
9.泌尿生殖系统：阴道念珠菌病、阴道炎、白带异常。
10.局部反应：注射部位炎症、注射部位疼痛、注射部位水肿、注射部位静脉炎。
用法用量
静滴，推荐起始剂量为100mg，以后每次50mg，每12h给药一次，静脉滴注30～60min。疗程根据感染部位和感染程度而定，一般5～14天。本品可用0.9%氯化钠注射液或5%葡萄糖注射液作为溶解液。本品50mg先用0.9%氯化钠注射液或5%葡萄糖注射液5ml溶解，再加到100ml输液中，使输液中药物浓度不超过lmg/ml。
制造和销售
辉瑞公司日本
原处方资料附件：http://www.info.pmda.go.jp/go/pack/6129400F1020_1_01/
日本上市产品：

美国上市产品：

替加环素是首个用于临床的甘氨酰环素（glycylcycline）类抗生素，由Francis Tally开发，Wyeth公司推上市场，2005年6月17日通过快速审批程序在美国获准。它在在细菌对抗生素耐药问题日趋严重——葡萄球菌和鲍曼不动杆菌流行的情势下应运而生，它对“超级细菌”新德里金属β-内酰胺酶新德里金属β-内酰胺酶多重耐药肠杆菌对替加环素敏感。其获准适应症为并发性皮肤和软组织感染、并发性腹腔感染和获得性细菌性肺炎。
Tygacil General Information
Tygacil (tigecycline) is a tetracycline-class antibacterial indicated for the treatment of infections caused by susceptible isolates of the designated microorganisms.
Tygacil is specifically indicated for the following conditions:
Complicated skin and skin structure infections caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes, Enterobacter cloacae, Klebsiella pneumoniae, and Bacteroides fragilis.
Complicated intra-abdominal infections caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros
Community-acquired bacterial pneumonia caused by Streptococcus pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, Haemophilus influenzae (betalactamase negative isolates), and Legionella pneumophila.
Tygacil is supplied as a lyophilized powder for reconstitution to intravenous infusions. The recommended initial dose is 100 mg, followed by 50 mg every 12 hours. Intravenous infusions of Tygacil should be administered over approximately 30 to 60 minutes every 12 hours.
Duration of treatment
The recommended duration of treatment with Tygacil for complicated skin and skin structure infections or for complicated intra-abdominal infections is 5 to 14 days. The recommended duration of treatment with Tygacil for community-acquired bacterial pneumonia is 7 to 14 days. The duration of therapy should be guided by the severity and site of the infection and the patient's clinical and bacteriological progress.
Tygacil Clinical Results
FDA Approval
The FDA approval of Tygacil for complicated skin and skin structure infections was based on two randomized, double-blind, active-controlled, multinational, multicenter studies (Studies 300 and 305). These studies compared Tygacil (100 mg intravenous initial dose followed by 50 mg every 12 hours) with vancomycin (1 g intravenous every 12 hours)/aztreonam (2 g intravenous every 12 hours) for 5 to 14 days. The primary efficacy endpoint was the clinical response at the test of cure visit (5-14 days after therapy) in the co-primary populations of the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) patients. The clinical cure rates (% of cured) were as follows:
Study 300: CE population: 82.9% for Tygacil; 82.3% for Vancomycin/Aztreonam. c-mITT population: 75.5% for Tygacil; 76.9% for Vancomycin/Aztreonam.
Study 305: CE population: 89.7% for Tygacil; 94.4% for Vancomycin/Aztreonam. c-mITT population: 84.3% for Tygacil; 86.9% for Vancomycin/Aztreonam.
The FDA approval of Tygacil for complicated intra-abdominal infections was based on two randomized, double-blind, active-controlled, multinational, multicenter studies (Studies 301 and 306). These studies compared Tygacil (100 mg intravenous initial dose followed by 50 mg every 12 hours) with imipenem/cilastatin (500 mg intravenous every 6 hours) for 5 to 14 days. The primary efficacy endpoint was the clinical response (% responding) at the test-of-cure visit for the microbiologically evaluable (ME) and the microbiologic modified intent-to-treat (m-mITT) co-primary populations. Study 301 ME: 80.6% vs. imipenem/cilastatin: 82.4%; m-mITT: 73.5% vs. imipenem/cilastatin: 78.2%. Study 306 ME: 91.3% vs. imipenem/cilastatin: 89.9%; m-mITT: 86.6% vs. imipenem/cilastatin: 84.6%.
The FDA approval of Tygacil for community-acquired pneumonia was based on two randomized, double-blind, active-controlled, multinational, multicenter studies (Studies 308 and 313). These studies compared Tygacil (100 mg intravenous initial dose followed by 50 mg every 12 hours) with levofloxacin (500 mg intravenous every 12 or 24 hours). In Study 308, after at least 3 days of intravenous therapy, a switch to oral levofloxacin (500 mg daily) was permitted for both treatment arms. Total therapy was 7 to 14 days. The primary endpoint was clinical response at the test of cure (TOC) visit in the co-primary populations of the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT). The clinical cure rates (% of cured) were as follows:
Study 308: CE population: 90.6% for Tygacil; 87.2% for Levofloxacin c-mITT population: 78% for Tygacil; 77.8% for Levofloxacin
Study 313: CE population: 88.9% for Tygacil; 85.3% for Levofloxacinc-mITT population: 83.7% for Tygacil; 81.5% for Levofloxacin.
Tygacil Side Effects
Adverse events associated with the use of Tygacil may include, but are not limited to, the following:
•Nausea
•Vomiting
•Diarrhea
•Infection
•Abdominal pain
•Headache
Tygacil Mechanism of Action
Tyhacil inhibits protein translation in bacteria by binding to the 30S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains. Tigecycline carries a glycylamido moiety attached to the 9-position of minocycline. The substitution pattern is not present in any naturally occurring or semisynthetic tetracycline and imparts certain microbiologic properties to tigecycline. In general, tigecycline is considered bacteriostatic; however, it has demonstrated bactericidal activity against isolates of S. pneumoniae and L. pneumophila.