原产地国家批准上市年份: 2014/09/01 英文适应病症1: Acute bacterial skin and skin structure infections caused by Gram-positive bacteria
临床试验期:
中文适应病症参考翻译1: 革兰氏阳性细菌引起的急性细菌性皮肤和皮肤结构感染
药品信息: ORBACTIV(奥利万星[oritavancin])注射用，为静脉使用
美国初次批准：2014
适应证和用途
ORBACTIV是一个脂糖肽类抗菌药适用为有急性细菌皮肤和皮肤结构感染引起或怀疑是被指定革兰氏阳性微生物易感分离株所致成年患者的治疗。 (1.1)
为了减低耐药细菌的发生和保持ORBACTIV和其他抗细菌药的有效性，ORBACTIV只应被用于治疗被证明或强烈怀疑是被易感细菌所致感染(1.2)
剂量和给药方法
历时3小时静脉输注给予一个1200 mg单次剂量剂量。(2.1)
剂型和规格
注射用：400 mg冻干粉在为重建一次性使用小瓶。(3)
禁忌证
⑴ ORBACTIV给药后48小时禁忌静脉注射普通肝素钠使用。(4.1，5.2)
⑵ 已知对ORBACTIV超敏性。(4.2，5.3)
警告和注意事项
⑴ 同时华法林[warfarin]使用：ORBACTIV和华法林的共同给药可能导致华法林的较高暴露，可能增加出血风险。在用慢性华法林治疗患者中只有当可被预期获益胜过可预期的出血风险时才使用ORBACTIV。(5.1)
⑵ 干扰凝固测试：曾显示ORBACTIV人为地延长aPTT至48小时，和可能延长PT和INR至24小时。 (5.2)
⑶ 曾报道使用抗菌药包括ORBACTIV超敏性反应。如发生急性超敏性征象终止输注。密切监视已知对糖肽类超敏性患者。(5.3)
⑷ 曾报道输注-相关反应。如发生输注反应减慢速率或中断输注(5.4)
⑸难辨梭状芽孢杆菌[Clostridium difficile]-伴随结肠炎：如发生腹泻评价患者。(5.5)
⑹ 骨髓炎：有确证或怀疑骨髓炎患者中开始适当另外抗细菌治疗。(5.6)
不良反应
用ORBACTIV治疗患者最常见不良反应(≥ 3%)是头痛，恶心，呕吐，肢体和皮下脓肿，和腹泻。(6.1)
为报告怀疑不良反应，联系Medicines公司电话1-888-977-6326或FDA电话1-800-FDA-1088或www.fda.gov/medwatch.
完整处方资料
1 适应证和用途
1.1 急性细菌性皮肤和皮肤结构感染
ORBACTIV™ (奥利万星[Oritavancin])注射用是适用为由下列易感分离株革兰氏阳性微生物所致急性细菌皮肤和皮肤结构感染(ABSSSI)成年患者的治疗：
金黄色葡萄球菌[Staphylococcus aureus](包括甲氧西林[methicillin]-易感和甲氧西林–耐药分离株)，化脓性链球菌[Streptococcus pyogenes]，无乳链球菌[Streptococcus agalactiae]，停乳链球菌[Streptococcus dysgalactiae]，咽峡炎链球菌[Streptococcus anginosus]群(包括咽颊炎链球菌，中间型链球菌,和星座链球菌)，和粪肠球菌[Enterococcus faecalis](万古霉素[vancomycin]-仅易感分离株)。
1.2 用法
为减少耐药细菌的发生发展和保持ORBACTIV和其他抗细菌药的有效性，ORBACTIV只应用于被证明或强烈怀疑被易感细菌所致的感染。当获得培育和易感性信息时，它们应在选择或修饰抗细菌治疗时被考虑。在缺乏这类数据，当地流行病学和易感性模式，经验选择治疗可能贡献。
2 剂量和给药方法
2.1 推荐剂量
在18岁和以上患者对ORBACTIV的推荐给药是单次1200 mg剂量历时3小时静脉输注给药。
2.2 对静脉输注ORBACTIV的制备
ORBACTIV是意向为静脉输注，只是重建和稀释后。
重建和稀释需要三个ORBACTIV 400 mg小瓶制备单次1200 mg静脉剂量。
重建：应使用无菌术重建3个ORBACTIV 400 mg小瓶。
● 加入40 mL无菌注射用水(WFI)重建每小瓶提供一个10 mg/mL溶液每小瓶。
● 对每个小瓶，轻轻旋转避免起泡和确保在溶液中所有ORBACTIV粉完全被重建。
● 重建后应肉眼观测每小瓶有无颗粒物质和应出现透明，无色至浅黄色溶液。
稀释：为稀释只使用5%葡萄糖无菌水(D5W)。不要使用生理盐水稀释因为它与ORBACTIV不相容和可能致药物沉淀。用无菌术：
●从1000 mL D5W静脉袋抽吸和遗弃120 mL。
● 从三个重建小瓶的各小瓶抽吸40 mL和加入至D5W静脉袋将袋容积至1000 mL。这产生浓度为1.2 mg/mL。
因为这个产品中不存在防腐剂或抑菌剂，在制备最终静脉溶液必须使用无菌术。
在室温贮存的输注袋中稀释的静脉溶液应在6小时内使用，或当在冰箱2至8°C(36至46°F)在 12小时内使用。组合贮存时间(小瓶中重建溶液和袋中稀释好溶液)和历时3小时输注时间在室温不应超过6小时或如在冰箱不超过12小时。
2.3 不兼容性
ORBACTIV是静脉给药。ORBACTIV只应在D5W被稀释。不要使用生理盐水稀释因它与ORBACTIV不相容和可能致药物沉淀。因此其他静脉物质，添加物或其他药物混合在生理盐水药物不应被加入至ORBACTIV一次用小瓶或通过相同静脉线同时输注或通过共同静脉端口。此外，在碱性或中性pH药物制剂可能与ORBACTIV不相容。
ORBACTIV不应与常用静脉药物同时通过共同静脉端口给药。如相同静脉线被序贯输注另外药物，该线应在ORBACTIV输注前和后用D5W冲洗。
3 剂型和规格
ORBACTIV以无菌，白色至灰白色冻干粉等于400 mg奥利万星在一次性使用50 mL透明玻璃小瓶供应。
4 禁忌证
4.1 静脉注射普通肝素钠
ORBACTIV给药后48小时禁忌使用静脉注射普通肝素钠因为ORBACTIV给药后活化部分凝血活酶时间(aPTT) 测试结果预期保持假性升高约48小时[见警告和注意事项(5.2)和药物相互作用(7.2)]。
4.2 超敏性
有已知对ORBACTIV超敏性患者禁忌ORBACTIV。
5 警告和注意事项
5.1 出血与华法林同时使用的潜在风险
ORBACTIV和华法林的共同给药可能导致华法林的较高暴露，可能增加出血风险。Use在用慢性华法林治疗患者只有当可预期获益胜过出血的风险时才应使用ORBACTIV 。频繁监视出血征象。[见药物相互作用(7.1)，临床药理学(12.3)]。
曾显示ORBACTIV人为地延长PT和INR至24小时，使监视华法林抗凝影响不可靠直至一次ORBACTIV剂量后24。[见警告和注意事项(5.2)]
5.2 凝血测试干扰
ORBACTIV曾显示人为地通过结合至和阻止激活凝固的磷酸脂质试剂的作用，激活在实验室共同使用凝固测试，延长aPTT共48小时和PT和INR共24小时。对ORBACTIV给药48小时内需要监视aPTT患者，一个非-磷酸脂质依赖凝固测试例如一个因子Xa(生色)试验或可能考虑不需要监测aPTT的另一种抗凝剂。
预期ORBACTIV对激活的凝血时间(ACT)影响因为这个凝固测试也利用磷酸脂质试剂。 ORBACTIV对凝固系统没有影响[见禁忌证(4.1)和药物相互作用(7.2)]。
5.3 超敏性
使用ORBACTIV曾报道严重超敏性反应。如ORBACTIV 输注期间发生一种急性超敏性反应，立即终止ORBACTIV和开始适当医护性支持。用ORBACTIV前，仔细询问关于既往对糖肽超敏性反应。由于交叉-敏感性的可能性，有糖肽过敏反应病史患者ORBACTIV输注期间仔细监测超敏性征象。在3期ABSSSI临床试验中，在ORBACTIV-治疗患者超敏性反应开始中位数为1.2天和这些反应的中位时间是2.4天[见不良反应(6.1)]。
5.4 输注相关反应
曾报道用ORBACTIV输注相关反应包括瘙痒，或潮红，如反应的确发生，考虑减慢或中断 ORBACTIV输注。[见不良反应(6.1)]
5.5 难辨梭状芽孢杆菌-伴腹泻
接近所有全身抗细菌药，包括ORBACTIV，都曾报道难辨梭状芽孢杆菌-伴腹泻(CDAD)和严重程度可能范围从轻度腹泻至致命性结肠炎。用抗菌药治疗改变结肠的正常的菌群和可能允许难辨梭状芽孢杆菌[难辨梭状芽孢杆菌]过度生长。难辨梭状芽孢杆菌产生毒素A和B对CDAD发展有贡献。难辨梭状芽孢杆菌的超毒素生产株致发病率和死亡率增加，因这些感染可能对抗细菌治疗难治和可能需要结肠切除术。使用抗菌药后所有存在腹泻患者必须考虑CDAD。需要仔细医疗病史因为曾报道在给予抗菌药后2个月以上发生CDAD。
如怀疑或确证CDAD，不是直接针对难辨梭状芽孢杆菌的抗菌使用可能需要终止。适当液体和电解质处理，蛋白补充，难辨梭状芽孢杆菌的抗菌治疗，和当临床指示应开始外科评价。
5.6 骨髓炎
在3期ABSSSI临床试验中，ORBACTIV治疗臂比万古霉素-治疗臂报告更多骨髓炎。监视患者骨髓炎体征和症状。如怀疑或诊断骨髓炎，开始适当另外抗细菌治疗[见不良反应(6.1)]。
5.7 耐药细菌的发生发展
在缺乏证明或强烈怀疑细菌感染处方ORBACTIV是可能对患者不提供获益和增加发生发展耐药细菌的风险[见患者咨询资料(17)]。
6 不良反应
在说明书的警告和注意事项节也讨论以下不良反应：
超敏性反应[见警告和注意事项(5.3)]
输注相关反应[见警告和注意事项(5.4)]
难辨梭状芽孢杆菌-伴腹泻[见警告和注意事项(5.5)]
骨髓炎[见警告和注意事项(5.6)]
ORBACTIV (oritavancin [oritavancin]) injection for intravenous use
Initial US Approval: 2014
Indications and Usage
ORBACTIV is a fat glycopeptide antibiotic suitable for acute bacterial skin and skin structure infections caused or suspected to be designated Gram-positive organisms susceptible isolates induced in adult patients. (1.1)
To reduce the incidence of drug-resistant bacteria and maintain the effectiveness ORBACTIV and other antibacterial drugs, ORBACTIV should only be used for the treatment proved or strongly suspected to be caused by susceptible bacterial infections (1.2)
Dosage and Administration
Which lasted 3 hours intravenous infusion a single dose of 1200 mg dose. (2.1)
DOSAGE FORMS AND STRENGTHS
Injection: 400 mg lyophilized powder in single-use vials for reconstruction. (3)
Contraindications
⑴ administered 48 hours after ORBACTIV contraindications to use of intravenous heparin ordinary. (4.1,5.2)
⑵ known to ORBACTIV hypersensitivity. (4.2,5.3)
Warnings and Precautions
⑴ Meanwhile warfarin [warfarin] Use: co-administration ORBACTIV and warfarin may result in higher warfarin exposure may increase the risk of bleeding. Used in the treatment of patients with chronic warfarin may be expected only when the benefit worth the risk of bleeding can be expected to use ORBACTIV. (5.1)
⑵ interfere with coagulation tests: once displayed ORBACTIV artificially prolong aPTT to 48 hours, and may be extended to 24 hours PT and INR. (5.2)
⑶ have reported the use of antimicrobial drugs, including ORBACTIV hypersensitivity reactions. In the event of termination signs of acute hypersensitivity infusion. Known to closely monitor the glycopeptide hypersensitivity patients. (5.3)
⑷ reported infusion - related reactions. Such as slowing the rate of infusion reactions occurred or interrupt infusion (5.4)
⑸ Clostridium difficile [Clostridium difficile] - accompanied by colitis: Evaluation of patients, such as the occurrence of diarrhea. (5.5)
⑹ osteomyelitis: There are confirmed or suspected osteomyelitis in patients with anti-bacterial treatment began appropriate addition. (5.6)
Adverse reactions
ORBACTIV patients with the most common adverse reactions (≥ 3%) are headache, nausea, vomiting, limb and subcutaneous abscesses, and diarrhea. (6.1)
To report suspected adverse reactions, contact The Medicines Company Phone 1-888-977-6326 or FDA telephone 1-800-FDA-1088 or www.fda.gov/medwatch.
Full prescribing information
1 INDICATIONS AND USAGE
1.1 acute bacterial skin and skin structure infections
ORBACTIV ™ (oritavancin [Oritavancin]) is suitable for injection by susceptible isolates of the following Gram-positive microorganisms caused by acute bacterial skin and skin structure infections (ABSSSI) treatment of adult patients with:
Staphylococcus aureus [Staphylococcus aureus] (including methicillin [methicillin] - susceptible and methicillin - resistant isolates), Streptococcus pyogenes [Streptococcus pyogenes], Streptococcus agalactiae [Streptococcus agalactiae], dysgalactiae streptococci [Streptococcus dysgalactiae], angina Streptococcus [Streptococcus anginosus] group (including Streptococcus anginosus, Streptococcus intermedius, and S. constellation), and Enterococcus faecalis [Enterococcus faecalis] (vancomycin [vancomycin ] - susceptible isolates only).
1.2 Usage
To reduce the development of drug-resistant bacteria and maintain the effectiveness of ORBACTIV and other anti-bacterial drugs, ORBACTIV applies only been proven or strongly suspected to be caused by susceptible bacterial infections. When obtaining the cultivation and susceptibility information, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns, experience the choice of treatment may contribute.
2 DOSAGE AND ADMINISTRATION
The recommended dose of 2.1
In patients over 18 years old and is the recommended dosing for ORBACTIV a single dose of 1200 mg intravenous infusion lasted three hours.
2.2 Preparation of the infusion ORBACTIV
ORBACTIV is the intention for intravenous infusion, but reconstruction and diluted.
Reconstruction and dilution requires three ORBACTIV 400 mg vial preparation of a single 1200 mg intravenous dose.
Reconstruction: aseptic technique should be used to rebuild three ORBACTIV 400 mg vial.
● added 40 mL of sterile water for injection (WFI) per vial rebuild a 10 mg / mL solution per vial.
● For each vial, gently rotate avoid foaming and to ensure that all ORBACTIV powder was completely rebuilt in the solution.
● After the reconstruction should be visually inspected for particulate matter and each vial should appear clear, colorless to pale yellow solution.
Dilution: dilution using only 5% dextrose in sterile water (D5W). Do not use saline dilution because it is precipitated with ORBACTIV incompatible and may cause drugs. Using sterile technique:
● From 1000 mL D5W intravenous bag suction and abandoned 120 mL.
● reconstruction from each vial three suction 40 mL vial and added to D5W intravenous bag to bag volume to 1000 mL. This results in a concentration of 1.2 mg / mL.
Because this product does not exist in preservatives or bacteriostatic agents, aseptic technique must be used in the preparation of the final intravenous solution.
Should be used within 6 hours of intravenous infusion of the solution stored at room temperature dilute the bag or when the refrigerator as 至 8 ° C (36 至 46 ° F) within 12 hours of use. Combination of storage time (reconstituted vial and diluted with a solution and the solution bag), and the infusion time for 3 hours at room temperature or not more than 6 hours, such as not more than 12 hours in the refrigerator.
2.3 Incompatibility
ORBACTIV intravenous administration. ORBACTIV should only be diluted in D5W. Do not use saline dilution because it precipitates with ORBACTIV incompatible and may cause drugs. So other intravenous substances, additives or other drugs mixed with a vial or a line simultaneously through the same intravenous infusion or by intravenous port in saline common drug should not be added to ORBACTIV. Furthermore, alkaline or neutral pH in the pharmaceutical formulation may be incompatible with ORBACTIV.
ORBACTIV commonly used intravenous drugs should not be administered simultaneously through a common intravenous port. The same vein as an infusion line is sequential addition of drugs, the line should be conducted before and after infusion with D5W ORBACTIV rinse.
3 DOSAGE FORMS AND STRENGTHS
ORBACTIV sterile, white to off-white lyophilized powder equivalent to 400 mg of oritavancin in disposable 50 mL clear glass vial supply.
4 contraindications
4.1 intravenous unfractionated heparin
ORBACTIV 48 hours after administration of intravenous unfractionated heparin is contraindicated because the ORBACTIV administration of activated partial thromboplastin time (aPTT) test results are expected to remain elevated for about 48 hours pseudo [see Warnings and Precautions (5.2) and drug interactions action (7.2)].
4.2 hypersensitivity
There are known to be contraindicated in patients with hypersensitivity ORBACTIV ORBACTIV.
5 WARNINGS AND PRECAUTIONS
5.1 Potential risk of bleeding with warfarin used simultaneously
Co-administration ORBACTIV and warfarin may result in higher warfarin exposure may increase the risk of bleeding. Use with chronic warfarin therapy in patients can be expected only if the benefit worth the risk of bleeding should be used ORBACTIV. Frequent monitoring signs of bleeding. [See Drug Interactions (7.1), Clinical Pharmacology (12.3)].
Has been shown to prolong artificially ORBACTIV PT and INR to 24 hours, so that the monitoring of anticoagulant effects of warfarin are not reliable until after the first dose ORBACTIV 24. [See Warnings and Precautions (5.2)]
5.2 interfere with blood clotting tests
ORBACTIV has been shown to artificially blocked by binding to and activating the role of lipid phosphate coagulation reagents, activated coagulation laboratory tests commonly used to extend a total of 48 hours aPTT and PT and INR total of 24 hours. ORBACTIV administered within 48 hours aPTT patients need to be monitored, a non - lipid phosphatase-dependent coagulation tests such as a factor Xa (chromophore) test or may not need to consider another anticoagulant monitoring the aPTT.
Expected ORBACTIV of activated clotting time (ACT) as the coagulation test can also affect the use of the lipid-phosphate reagents. ORBACTIV no effect on the clotting system [see Contraindications (4.1) and Drug Interactions (7.2)].
5.3 hypersensitivity
Use ORBACTIV have reported severe hypersensitivity reactions. As occurred during ORBACTIV an acute hypersensitivity infusion reactions, immediately terminate ORBACTIV and start appropriate medical support. With former ORBACTIV, careful inquiry about previous glycopeptide hypersensitivity reactions. Because of the cross - the possibility of sensitivity, there are glycopeptides allergic reactions during infusion ORBACTIV carefully monitored in patients with a history of hypersensitivity signs. In three ABSSSI clinical trials, patients treated in ORBACTIV- hypersensitivity reaction started a median of 1.2 days and the median time for these reactions is 2.4 days [see Adverse Reactions (6.1)].
5.4 infusion-related reactions
Have been reported with ORBACTIV infusion related reactions, including itching, or flushing, such as the reaction does occur, consider slowing or interruption ORBACTIV infusion. [See Adverse Reactions (6.1)]
5.5 Clostridium difficile - associated diarrhea
Close to all systemic antibacterial agents, including ORBACTIV, have reported Clostridium difficile - associated diarrhea (CDAD) and the severity may range from mild diarrhea to fatal colitis. The normal flora of the colon with antibiotic treatment and the change could allow Clostridium difficile [Clostridium difficile] overgrowth. Clostridium difficile toxin A and B contribute to the development for CDAD. Clostridium difficile toxin-producing strains caused by ultra-morbidity and mortality due to these infections may fight bacteria treatment of refractory and may require colectomy. After the use of antimicrobial drugs must be considered for all patients with diarrhea, the presence of CDAD. After requires careful medical history as reported in the administration of antibacterial agents CDAD occurred two months or more.
If the suspected or confirmed CDAD, is not directed against C. difficile may need to stop using anti-bacterial. Appropriate fluid and electrolyte handling, protein supplements, Clostridium difficile antimicrobial therapy, and when clinically indicated surgical evaluation should begin.
5.6 osteomyelitis
In three clinical trials ABSSSI, ORBACTIV vancomycin treatment arm ratio - Treatment Arm to report more osteomyelitis. Monitoring signs and symptoms in patients with osteomyelitis. If you suspect or diagnose osteomyelitis, start the appropriate addition of anti-bacterial treatment [see Adverse Reactions (6.1)].
5.7 the development of drug-resistant bacteria
In the absence of proven or strongly suspected bacterial infection prescription ORBACTIV is likely to benefit and increase the risk of development of drug-resistant bacteria in the patient does not provide [see Patient Counseling Information (17)].
6 ADVERSE REACTIONS
Warnings and Precautions section of the manual also discusses the following adverse reactions:
Hypersensitivity reactions [see Warnings and Precautions (5.3)]
Infusion-related reactions [see Warnings and Precautions (5.4)]
Clostridium difficile - associated diarrhea [see Warnings and Precautions (5.5)]
Osteomyelitis [see Warnings and Precautions (5.6)]
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