新型抗菌药SIVEXTRO(TEDIZOLID PHOSPHATE)TABLET ORAL获FDA批准上市 6月20日，美国FDA批准新型抗菌药物Sivextro (tedizolid phosphate)用于治疗皮肤感染成人患者。Sivextro被批准用于治疗由某些敏感细菌，如金黄色葡萄球菌（包括耐甲氧西林菌株和甲氧西林敏感菌株）、各种链球菌和粪肠球菌引起的急性细菌性皮肤及皮肤组织感染(ABSSSI)。Sivextro以静脉注射和口服给药 Sivextro是过去一个月内FDA批准用于治疗ABSSSI的第二款新型抗菌药物。5月23日，FDA批准达巴万星，这款药物同样用于治疗金黄色葡萄球菌和各种链球菌引起的ABSSSI患者。“今天的批准为医师和患者提供了一种新的严重皮肤感染治疗选择，”FDA药品评价与研究中心抗菌产品办公室主任、医学博士、公共卫生学硕士Cox表示说。 Sivextro旨在治疗严重或危及生命的感染，其上市申请被授予合格感染疾病产品(QIDP)资格，并获得了FDA的加快审评。Sivextro的QIDP资格使这款药物除了拥有《食品、药品和化妆品法案》赋予的市场独占权之外，还可以拥有额外5年的市场独占权。 Sivextro的安全性及有效性在1315名ABSSSI成人患者参与的两项临床试验中得到评价。受试者被随机配给Sivextro或另一种获批用于治疗ABSSSI的抗菌药物利奈唑胺。结果显示，Sivextro治疗ABSSSI与利奈唑胺同样有效。 临床试验中证实的最常见副作用有恶心、头痛、腹泻、呕吐和头晕。Sivextro的安全性和有效性尚未在白细胞水平降低（ 嗜中性白血球减少症）的患者中进行评价，所以应该考虑替代疗法。 SIVEXTRO® (tedizolid phosphate) tablets, 200 mg Sivextro (tedizolid phosphate) is an antibacterial agent of the oxazolidinone class. Sivextro is specifically indicated for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus Group (including Streptococcus inosus, Streptococcus intermedius, and Streptococcus constellatus), and Enterococcus faecalis. Sivextro is supplied as a tablet or solution, for oral and/or intravenous administration. The recommended dosage of Sivextro is 200 mg administered once daily for six (6) days either orally (with or without food) or as an intravenous (IV) infusion. SIVEXTRO Rx Pharmacological Class: Oxazolidinone. Active Ingredient(s): Tedizolid phosphate 200mg; tablets; and lyophilized pwd for IV infusion after reconstitution; preservative-free. Company Cubist Pharmaceuticals, Inc. Indication(s): Acute bacterial skin and skin structure infections (ABSSSI) caused by the following susceptible Gram (+) organisms: Staphylococcus aureus (including MRSA and MSSA), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus Group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), and Enterococcus faecalis. Pharmacology: Tedizolid phosphate is a prodrug that is converted by phosphatases to tedizolid, the microbiologically active moiety, following oral and intravenous administration. The antibacterial activity of tedizolid is mediated by binding to the 50S subunit of the bacterial ribosome resulting in inhibition of protein synthesis. Tedizolid inhibits bacterial protein synthesis through a mechanism of action different from other non-oxazolidinone class antibiotics. In vitro time-kill studies show that tedizolid is bacteriostatic against enterococci, staphylococci, and streptococci. Clinical Trials: A total of 1,315 adults with ABSSSI were randomized in two multicenter, multinational, double-blind, non-inferiority trials. Both trials compared Sivextro 200mg once daily for 6 days vs. linezolid 600mg every 12 hours for 10 days. In Trial 1, patients were treated with oral therapy, while in Trial 2, patients could receive oral therapy after a minimum of one day of intravenous therapy. Patients with cellulitis/erysipelas, major cutaneous abscess, or wound infection were enrolled in the trials. In Trial 1, patients with ABSSSI were randomized to Sivextro (N=323) and to linezolid (N=326). The primary endpoint was early clinical response defined as no increase from baseline lesion area at 48–72 hours after the first dose and oral temperature of  ≤ 37.6° C, confirmed by a second temperature measurement within 24 hours in the intent-to-treat (ITT) population. The treatment difference was 0.1 (95% CI: −6.2, 6.3) between responders in the Sivextro 200mg (n=256) and linezolid 1200mg (n=258) treatment groups. In Trial 2, patients with ABSSSI were randomized to Sivextro (N=332) and to linezolid (N=334). The primary endpoint was early clinical response defined as ≥ 20% decrease from baseline lesion area at 48–72 hours after the first dose in the ITT population. The treatment difference was 2.6 (95% CI: −3.0, 8.2) between responders in the Sivextro 200mg (n=283) and linezolid 1200mg (n=276) treatment groups. An investigator assessment of clinical response was made at the post-therapy evaluation (7–14 days after end of therapy) in the intent-to-treat and clinically evaluable populations. Clinical success was defined as resolution or near resolution of most disease-specific signs and symptoms, absence or near resolution of systemic signs of infection if present at baseline, and no new signs, symptoms, or complications attributable to the ABSSSI requiring further treatment of the primary lesion. For more clinical trial data, see full labeling. Legal Classification: Rx Adults: ≥18 years: Oral: 200mg once daily for 6 days. IV: Infuse 200mg once daily over 1 hour for 6 days. If switching from IV to oral: no dose adjustment necessary. Children: <18 years: not established. Warnings/Precautions: Not adequately evaluated in patients with neutropenia (ANC <1000 cells/mm3); consider alternate therapies. Risk of Clostridium difficile-associated diarrhea (CDAD); discontinue if suspected or confirmed. Pregnancy (Category C). Nursing mothers. Adverse Reaction(s) Nausea, headache, diarrhea, vomiting, dizziness. How Supplied: Tabs—6 (blister pack), 30; single-use vials—10 LAST UPDATED: 8/25/2014 本品研究资料附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=75672079-589f-451a-bdbf-eaebcfcc80a9 Sivextro(通用名：tedizolid磷酸盐，曾用名：TR-701)由Cubist制药公司开发，是一种恶唑烷酮类抗生素。Sivextro是一种前药，在体内可被磷酸酶迅速转化为具有生物活性的tedizolid。后者能够和细菌的核糖体50S亚基结合，从而抑制蛋白质的合成。尽管自2000年辉瑞的同类抗菌素利奈唑胺获得美国FDA批准以后，至少有10个同类化合物进入临床，但Sivextro是第一个获得FDA批准的二代恶唑烷酮类抗生素。和一代产品利奈唑胺相比，Sivextro对一些细菌的体外抑制活性要高2-8倍，安全性在一定程度上也有所提高。 中文名称: 磷酸泰地唑胺 英文名称:Tedizolid phosphate 化学名：((5R)-3-(3-Fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-2-oxooxazolidin-5-yl)methyl hydrogen phosphate, TR-701 FA, Tedizolid phosphate, Torezolidphosphate, UNII-O7DRJ6R4DW 分子量：450.317705 g/mol 分子式：C17H16FN6O6P Indication and Important Safety Information SIVEXTRO® (tedizolid phosphate) is indicated for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group (including Streptococcus anginosus, Streptococcus intermedius and Streptococcus constellatus), and Enterococcus faecalis. Usage To reduce the development of drug-resistant bacteria, only use SIVEXTRO for ABSSSI proven or strongly suspected to be caused by susceptible bacteria through the use of culture and susceptibility information or local epidemiology and susceptibility patterns. Warnings and Precautions Patients with neutropenia: The safety and efficacy of SIVEXTRO in patients with neutropenia (neutrophil counts <1000 cells/mm3) have not been adequately evaluated. In an animal model of infection, the antibacterial activity of SIVEXTRO was reduced in the absence of granulocytes. Alternative therapies should be considered when treating patients with neutropenia. Clostridium difficile–associated diarrhea (CDAD), ranging from mild diarrhea to fatal colitis, has been reported with nearly all systemic antibacterial agents, including SIVEXTRO. Careful medical history is necessary because CDAD has been reported to occur more than two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterial use not directed against C. difficile should be discontinued, if possible. Development of drug-resistant bacteria: Prescribing SIVEXTRO in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Adverse Reactions The most common adverse reactions for SIVEXTRO are nausea, headache, diarrhea, vomiting, and dizziness.