2017年8月30日，美国制药公司The Medicines Company表示，美国FDA批准了公司VABOMERE注射剂（美罗培南+VABOMERE）用于成人复杂性尿路感染（cUTI）的治疗，包括由敏感肠杆菌（大肠杆菌、克雷白氏杆菌、阴沟肠杆菌）引起的肾盂肾炎。VABOMERE由美罗培南（一种抗菌药物）和vaborbactam（可以抑制某些细菌的耐药性）组成。
VABOMERE可以应对产生了β-内酰胺酶的革兰氏阴性菌的感染，这类细菌在美国和欧洲传播广泛，尤其是产生肺炎克雷伯菌碳青霉烯酶(KPC)的细菌。产生KPC酶让肠杆菌科细菌对大量的碳青霉烯抗生素产生耐药，并已经被美国疾病控制中心列为紧急抗菌素耐药性威胁。
VABOMERE获得了FDA的优先审评资格并被授予合格传染病产品（QIDP）认定，这次获得批准，VABOMERE将拥有5年的市场独占期，这意味着该药物美国地区的专利权及排他性将会到2031年。VABOMERE由The Medicines Company的感染疾病业务部开发，是对该公司感染类疾病产品线的强力补充。
The Medicines Company公司首席执行官Clive Meanwell博士表示：“我们非常高兴FDA加速批准了VABOMERE用于cUTI的治疗，以让该药物可以尽快被医生及患者应用，降低这类高风险病患的死亡率。VABOMERE是用于对抗产生了KPC酶肠杆菌科细菌的新的治疗选择，该领域目前还没有较好的治疗手段。我们将充分利用公司已经建立的商业化团队并期待VABOMERE在美国的正式上市，同时我们还会寻求VABOMERE在更多国家的注册许可。”
匹兹堡大学感染疾病副教授、VA匹兹堡健康系统感染科负责人Cornelius Clancy博士评论道：“碳青霉烯类抗生素是治疗严重细菌感染的首选药物，例如复杂性尿路感染这种肠杆菌导致的、超广谱β-内酰胺酶为特点的感染的治疗。随着KPC酶的扩散，可以克服碳青霉烯类药物耐药机制的新的抗菌药将会得到认可。”
VABOMERE获得批准的支持数据来自TANGO-1研究，这是一项多中心、随机、双盲、双模拟临床3期试验，研究了VABOMERE相比哌拉西林-他唑巴坦治疗复杂性尿路感染（包括急性肾盂肾炎）的有效性、安全性及耐受情况。试验共入组了550名成人患者，被随机按照1:1分别接受每8小时内3个小时的VABOMERE (美罗培南 2g-vaborbactam 2g)静脉注射治疗或每8小时内30分钟的哌拉西林4g–他唑巴坦 500mg的治疗，两组患者均持续治疗10天以上。
该项研究在微生物学上意向治疗群体(m-mITT)中进行了主要的评估，主要疗效终点被定义为“临床结果的整体成功”（治愈或改善）以及微生物学的根除结果（基线细菌病原体降低到< 104 CFU/ml）。整体试验成功结果方面，VABOMERE组有183/186 名患者 (98.4%)达到该标准，哌拉西林-他唑巴坦组达到该标准的人数为165/175 名患者 (94.3%)，两组有4.1%的差异（95% CI: 0.3% - 8.8%）。VABOMERE组最常见不良反应有头痛、注射部位不适和腹泻。
VABOMERE(meropenem and vaborbactam) for injection
VABOMERE™ (meropenem and vaborbactam) for injection, for intravenous use
Initial U.S. Approval: 2017
INDICATIONS AND USAGE
VABOMERE (meropenem and vaborbactam) is a combination of meropenem, a penem antibacterial, and vaborbactam, a beta‑lactamase inhibitor, indicated for the treatment of patients 18 years and older with complicated urinary tract infections (cUTI) including pyelonephritis caused by designated susceptible bacteria. (1.1)
To reduce the development of drug‑resistant bacteria and maintain the effectiveness of VABOMERE and other antibacterial drugs, VABOMERE should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. (1.2)
DOSAGE AND ADMINISTRATION
Administer VABOMERE 4 grams (meropenem 2 grams and vaborbactam 2 grams) every 8 hours by intravenous infusion over 3 hours for up to 14 days, in patients 18 years of age and older with an estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m2. (2.1)
Dosage adjustment is recommended in patients with renal impairment who have an eGFR less than 50 mL/min/ 1.73m2. (2.2)
|
eGFRa (mL/min/ 1.73m2)
|
Recommended Dosage Regimen for VABOMERE
(meropenem and vaborbactam) b, c, d
|
Dosing Interval
|
|
30 to 49
|
VABOMERE 2 grams (meropenem 1 gram and vaborbactam 1 gram)
|
Every 8 hours
|
|
15 to 29
|
VABOMERE 2 grams (meropenem 1 gram and vaborbactam 1 gram)
|
Every 12 hours
|
|
Less than 15
|
VABOMERE 1 gram (meropenem 0.5 grams and vaborbactam 0.5 grams)
|
Every 12 hours
|
a As calculated using the Modification of Diet in Renal Disease (MDRD) formula; b All doses of VABOMERE are administered intravenously over 3 hours; c Doses adjusted for renal impairment should be administered after a hemodialysis session; d The total duration of treatment is for up to 14 days.
See Full Prescribing Information for instructions for constituting supplied dry powder and subsequent required dilution. (2.3)
See Full Prescribing Information for drug compatibilities. (2.4)
DOSAGE FORMS AND STRENGTHS
VABOMERE 2 grams (meropenem and vaborbactam) for injection, is supplied as a sterile powder for constitution in single‑dose vials containing meropenem 1 gram (equivalent to 1.14 grams of meropenem trihydrate) and vaborbactam1 gram. (3)
CONTRAINDICATIONS
Known hypersensitivity to the components of VABOMERE (meropenem and vaborbactam) or anaphylactic reactions to beta‑lactams. (4)
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions were reported with the use of VABOMERE. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterial drugs. Discontinue infusion if signs of acute hypersensitivity occur. (5.1)
Seizures and other adverse Central Nervous System experiences have been reported during treatment with meropenem, a component of VABOMERE. (5.2)
Clostridium difficile-associated diarrhea has been reported with nearly all systemic antibacterial agents, including VABOMERE. eva luate patients if diarrhea occurs. (5.3)
Co-administration of meropenem with valproic acid or divalproex sodium reduces the serum concentration of valproic acid potentially increasing the risk of breakthrough seizures. (5.4, 7.1)
ADVERSE REACTIONS
The most frequently reported adverse reactions occurring in ≥3% of patients treated with VABOMERE were headache, phlebitis/infusion site reactions, and diarrhea. (6.1)
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
1.1 Complicated Urinary Tract Infections (cUTI), including Pyelonephritis
VABOMERE™ is indicated for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTI) including pyelonephritis caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae species complex.
1.2 Usage
To reduce the development of drug-resistant bacteria and maintain the effectiveness of VABOMERE and other antibacterial drugs, VABOMERE should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosage
The recommended dosage of VABOMERE is 4 grams (meropenem 2 grams and vaborbactam 2 grams) administered every 8 hours by intravenous (IV) infusion over 3 hours in patients 18 years of age and older with an estimated glomerular filtration rate (eGFR) greater than or equal to 50 mL/min/1.73m2. The duration of treatment is for up to 14 days.
2.2 Dosage Adjustments in Patients with Renal Impairment
Dosage adjustment is recommended in patients with renal impairment who have an eGFR less than 50 mL/min/1.73m2. The recommended dosage of VABOMERE in patients with varying degrees of renal function is presented in Table 1. For patients with changing renal function, monitor serum creatinine concentrations and eGFR at least daily and adjust the dosage of VABOMERE accordingly [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Meropenem and vaborbactam are removed by hemodialysis [see Clinical Pharmacology (12.3)]. For patients maintained on hemodialysis, administer VABOMERE after a hemodialysis session.
Table 1: Dosage of VABOMERE in Patients with Renal Impairment
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eGFRa
(mL/min/
1.73m2)
|
Recommended Dosage Regimen for VABOMERE
(meropenem and vaborbactam) b, c, d
|
Dosing Interval
|
|
30 to 49
|
VABOMERE 2 grams (meropenem 1 gram and vaborbactam 1 gram)
|
Every 8 hours
|
|
15 to 29
|
VABOMERE 2 grams (meropenem 1 gram and vaborbactam 1 gram)
|
Every 12 hours
|
|
Less than 15
|
VABOMERE 1 gram (meropenem 0.5 grams and vaborbactam 0.5 grams)
|
a As calculated using the Modification of Diet in Renal Disease (MDRD) formula as follows: eGFR (mL/min/1.73m2) = 175 x (serum creatinine)-1.154 x (age)-0.203x (0.742 if female) x (1.212 if African American)
b All doses of VABOMERE are administered intravenously over 3 hours.
c Doses adjuste
