近日，美国食品和药物管理局（FDA）已批准ZEMDRI（plazomicin）用于患有复杂性尿路感染（cUTI）的成人，包括肾盂肾炎，由具有有限或无替代治疗选择的患者的某些肠杆菌科引起。 ZEMDRI是静脉输注，每日一次。
批准日期：2018年6月28日 公司：Achaogen公司
ZEMDRI（plazomicin）注射液，用于静脉注射
美国最初批准：2018年
警告：
NEPHROTOXICITY，OTOTOXICITY，
神经肌肉阻滞和胎儿危害
查看完整的盒装警告的完整处方信息。
•ZEMDRI报告了肾毒性。肾功能受损患者，老年人和接受伴随肾毒性药物治疗的患者肾毒性风险更大。
•ZEMDRI报告了耳毒性，表现为听力丧失，耳鸣和/或眩晕。氨基糖苷类相关的耳毒性的症状可能是不可逆的，并且可能在治疗完成后才变得明显。
•氨基糖甙类药物与神经肌肉阻滞有关。在使用ZEMDRI治疗期间，监测与神经肌肉阻滞相关的有关反应
特别是在高危患者中。
•氨基糖甙类药物，包括ZEMDRI，可能会对孕妇造成胎儿伤害。
作用机制
ZEMDRI是一种抗菌药物[见微生物学]。
适应症和用法
ZEMDRI是一种氨基糖苷类抗菌药，适用于治疗18岁或以上患有包括肾盂肾炎的复杂尿路感染（cUTI）的患者。
由于仅提供有限的临床安全性和有效性数据，reserveZEMDRI用于具有有限或无替代治疗选择的患者。
为了减少耐药细菌的发展和ZEMDRI及其他抗菌药物的维持有效性，ZEMDRI应该仅用于治疗被易感微生物证实或强烈预防的感染。
剂量和给药
•对于18岁或18岁以上，胰岛素清除率大于或等于90mL/min的患者，通过静脉内（IV）输注30分钟，每24小时给予ZEMDRI 15mg/kg。
•推荐的治疗时间为4至7天，包括肾盂肾炎。
•在开始治疗前和治疗期间每天评估所有患者的肌酐清除率。
•针对肾功能改善患者的推荐初始剂量方案如下表所示。
估计CLcr：a（mL/分钟）  推荐的ZEMDRI用量：b   给药间隔
    大于或等于60至小于90        15毫克/千克              每24小时一次
    大于或等于30至小于60        10毫克/千克              每24小时一次
    大于或等于15至小于30        10毫克/千克              每24小时一次
a根据Cockcroft-Gault公式估计的CLcr。
b使用总体重（TBW）计算剂量。对于TBW大于IBW 25％或更多的患者，使用调整后的体重。
•根据肾功能或治疗药物监测（TDM）的变化，查看完整处方信息以进行后续剂量调整。
•有关溶液制备，静脉输液稳定性和药物相容性的说明，请参阅完整处方信息。
剂量形式和强度
ZEMDRI注射液500 mg/10mL（50mg/mL）是含有相当于500mg plazomicin游离碱的单剂量小瓶硫酸盐。
禁忌症
对已知对任何氨基糖苷类过敏的患者禁用ZEMDRI。
警告和注意事项
•过敏反应，包括过敏反应：报告的有机磷脂酰肌醇。如果发生过敏反应，请停用ZEMDRI。
•艰难梭菌相关性腹泻：报告几乎所有系统性抗菌药物。评估腹泻是否发生。
不良反应
最常见的不良反应（≥1％的患者接受ZEMDRI治疗）是肾功能下降，腹泻，高血压，头痛，恶心，呕吐和低血压。
包装提供/存储和处理
如何提供
ZEMDRI注射液500毫克/10毫升（50毫克/毫升）以单剂量，10毫升小瓶供应，配有翻盖式密封，蓝色聚丙烯按钮为透明，无色至黄色，无菌溶液。每个小瓶含有相当于500mg plazomicin游离碱的硫酸plazomicin，在注射用水中浓度为50mg/mL的plazomicin。每个小瓶含有氢氧化钠，用于将pH调节至6.5。溶液可能变成黄色; 这并不表示效力下降。
NDC编号包装/容量单位每箱Plazomicin content71045-010-02一次性，翻盖小瓶，10mL 10 500mg，10mL（50mg/mL）
存储和处理
储存ZEMDRI注射剂500mg/10mL（50mg/mL），在2°C至8°C（36°F至46°F）冷藏。
完整处方资料附件：http://zemdri.com/assets/pdf/Prescribing-Information.pdf

ZEMDRI(plazomicin) Approved by FDA for the Treatment of Adults with Complicated Urinary Tract Infections (cUTI)
U.S. Food and Drug Administration (FDA) has approved ZEMDRI™ (plazomicin) for adults with complicated urinary tract infections (cUTI), including pyelonephritis, caused by certain Enterobacteriaceae in patients who have limited or no alternative treatment options. ZEMDRI is an intravenous infusion, administered once daily.
“The approval of ZEMDRI marks a significant milestone for Achaogen and we are excited to offer healthcare practitioners a new treatment option for patients with certain serious bacterial infections. ZEMDRI is designed to retain its potent activity in the face of certain difficult-to-treat MDR infections, including CRE and ESBL- producing Enterobacteriaceae,” said Blake Wise, Achaogen’s Chief Executive Officer. “Today's milestone was made possible by our employees, by patients and investigators involved in our clinical trials, and by BARDA, who contributed significant funding for the development of ZEMDRI. This marks an important step in our commitment to fighting MDR bacteria and we are excited to launch ZEMDRI, a much needed once-daily antibiotic.”
INDICATIONS & USAGE
ZEMDRI (plazomicin) is indicated in patients 18 years of age or older for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis caused by the following susceptible microorganism(s): Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae.
As only limited clinical safety and efficacy data for ZEMDRI are currently available, reserve ZEMDRI for use in cUTI patients who have limited or no alternative treatment options.
To reduce the development of drug-resistant bacteria and maintain effectiveness of ZEMDRI and other antibacterial drugs, ZEMDRI should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible microorganisms.
Contraindications
ZEMDRI is contraindicated in patients with known hypersensitivity to any aminoglycoside.
Additional Warnings and Precautions
Nephrotoxicity: Reported with the use of ZEMDRI. Most serum creatinine increases were ≤1 mg/dL above baseline and reversible. Assess CLcr in all patients prior to initiating therapy and daily during therapy with ZEMDRI, particularly in those at increased risk of nephrotoxicity, such as those with renal impairment, the elderly and those receiving concomitant potentially nephrotoxic medications. In the setting of worsening renal function, the benefit of continuing ZEMDRI should be assessed. Adjust the initial dosage regimen in cUTI patients with CLcr ≥15 mL/min and <60 mL/min. For subsequent doses, TDM is recommended for patients with CLcr ≥15 mL/min and <90 mL/min.
Ototoxicity: Reported with ZEMDRI (manifested as hearing loss, tinnitus, and/or vertigo). Symptoms of aminoglycoside-associated ototoxicity may be irreversible and may not become evident until after completion of therapy. Aminoglycoside-associated ototoxicity has been observed primarily in patients with a family history of hearing loss (excluding age-related hearing loss), patients with renal impairment, and in patients receiving higher doses and/or for longer periods than recommended. The benefit-risk of ZEMDRI therapy should be considered in these patients.
Neuromuscular Blockade: Aminoglycosides have been associated with exacerbation of muscle weakness in patients with underlying neuromuscular disorders, or delay in recovery of neuromuscular function in patients receiving concomitant neuromuscular blocking agents. During therapy with ZEMDRI, monitor for adverse reactions associated with neuromuscular blockade, particularly in high-risk patients, such as patients with underlying neuromuscular disorders (including myasthenia gravis) or those patients concomitantly receiving neuromuscular blocking agents.
Fetal Harm: Aminoglycosides, including ZEMDRI, can cause fetal harm when administered to a pregnant woman. Patients who use ZEMDRI during pregnancy, or become pregnant while taking ZEMDRI should be apprised of the potential hazard to the fetus.
Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving aminoglycoside antibacterial drugs. Before therapy with ZEMDRI is instituted, careful inquiry about previous hypersensitivity reactions to other aminoglycosides should be made. Discontinue ZEMDRI if an allergic reaction occurs.
Clostridium difficile-Associated Diarrhea (CDAD): Reported for nearly all systemic antibacterial drugs and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial drugs alters the normal flora of the colon and may permit overgrowth of C. difficile. Careful medical history is necessary. If CDAD is suspected or confirmed, antibacterial drugs not directed against C. difficile may need to be discontinued.
Development of Drug-Resistant Bacteria: Prescribing ZEMDRI in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
The most common adverse reactions (≥1% of patients treated with ZEMDRI) are decreased renal function, diarrhea, hypertension, headache, nausea, vomiting and hypotension.