近日，FDA批准新型抗生素Orbactiv（oritavancin，奥利万星，IV）注射液，用于由敏感革兰氏阳性菌（包括耐甲氧西林金黄色葡萄球菌，MRSA）导致的急性细菌性皮肤和皮肤结构感染（ABSSSIs）成人患者的治疗。
Orbactiv是FDA批准用于ABSSSIs治疗的首个和唯一一种单剂量治疗方案的抗生素。患者仅接受一次Orbactiv输液，整个治疗方案便已结束。此次Orbactiv的获批，也代表着细菌性皮肤和皮肤结构感染疾病治疗方面远超当前临床标准的重大进步。目前，患者往往需要多次静脉输注抗生素，而Orbactiv单剂量治疗方案，将显著减少患者的剂量负担。
批准日期：2014年8月6日 公司：The Medicines公司
ORBACTIV（奥利万星[oritavancin]）用于注射，用于静脉注射
美国最初批准：2014年
最近的重大变化
禁忌症：1/2016
警告和注意事项：1/2016
警告和注意事项：10/2016
作用机制
Oritavancin是一种抗菌药物[见临床药理学]。
适应症和用法
ORBACTIV是一种lipoglycopeptide抗菌药物，适用于治疗成人患者的急性细菌性皮肤和皮肤结构感染，这些感染是由易感的指定革兰氏阳性微生物分离株引起或怀疑引起的。
为了减少耐药细菌的发展并保持ORBACTIV和其他抗菌药物的有效性，ORBACTIV应该仅用于治疗被证实或强烈怀疑由易感细菌引起的感染。
剂量和给药
通过静脉内输注在3小时内施用1200mg单剂量。
剂量形式和强度
用于注射：在一次性小瓶中用于重构的400mg冻干粉末。
禁忌症
在ORBACTIV给药后120小时（5天）禁止使用静脉内普通肝素钠。
已知对ORBACTIV的超敏反应。
警告和注意事项
凝血试验干扰：ORBACTIV已显示人工延长aPTT长达120小时，并可延长PT和INR长达12小时，ACT长达24小时。对于在ORBACTIV给药120小时内需要进行aPTT监测的患者，可考虑非磷脂依赖性凝血试验，如因子Xa（显色）试验或不需要aPTT的替代抗凝剂。
已经报道了使用包括ORBACTIV的抗菌剂的超敏反应。如果出现急性超敏反应的迹象，则停止输注。密切监测已知对糖肽过敏的患者。
已报道输注相关反应。如果输液反应发生，则减慢速度或中断输液。
艰难梭菌相关性腹泻：如果发生腹泻，评估患者。
同时使用华法林：ORBACTIV已被证明可以人工延长PT/INR长达12小时。如果同时接受ORBACTIV和华法林，应监测患者的出血情况。
骨髓炎：对确诊或疑似骨髓炎患者进行适当的替代抗菌治疗。
不良反应
用ORBACTIV治疗的患者最常见的不良反应（≥3％）是头痛，恶心，呕吐，肢体和皮下脓肿，以及腹泻。
包装提供/存储和处理
提供/存储
ORBACTIV作为单次使用的50mL容量玻璃小瓶提供，其含有相当于400mg奥利万星的无菌冻干粉末（NDC 65293-015-01）。 将三个小瓶包装在纸箱中以提供单次1200mg剂量处理（NDC 65293-015-03）。
ORBACTIV样品瓶应储存在20°C至25°C（68°F至77°F）的温度下; 允许偏移15°C至30°C（59°F至86°F）[见USP，受控室温（CRT）]。
ORBACTIV(oritavancin)for injection, for intravenous use
Initial U.S. Approval: 2014
Usual Diluents
[Single dose]
[1200mg] [880ml] [3hours]   
(Total volume = 1000ml.  Concentration=1.2mg/mL)
Reconstitution: Aseptic technique should be used to reconstitute three ORBACTIV 400 mg vials.
Add 40 mL of sterile water for injection(WFI)to reconstitute each vial to provide a 10mg/mL solution per vial.
For each vial, gently swirl to avoid foaming and ensure that all ORBACTIV powder is completely reconstituted in solution. Each vial should be inspected visually for particulate matter after reconstitution and should appear to be clear, colorless to pale yellow solution.
Dilution: Use ONLY 5% dextrose in sterile water (D5W) for dilution. Do NOT use Normal Saline for dilution as it is incompatible with ORBACTIV and may cause precipitation of the drug. Use aseptic technique to:
Withdraw and discard 120 mL from a 1000 mL intravenous bag of D5W.
Withdraw 40 mL from each of the three reconstituted vials and add to D5W intravenous bag to bring the bag volume to 1000 mL. This yields a concentration of 1.2 mg/mL.
WARNINGS
See warnings and precautions below.
Description:
ORBACTIV (oritavancin) for injection contains oritavancin diphosphate, a semisynthetic lipoglycopeptide antibacterial drug.
The chemical name for oritavancin is [4"R]-22-O-(3-amino-2,3,6-trideoxy-3-C-methyl-a-L-arabino-hexopyranosyl)-N3''-[(4'-chloro[1,1'-biphenyl]-4-yl)methyl] vancomycin phosphate [1:2] [salt]. The empirical formula of oritavancin diphosphate is C86H97N10O26Cl3•2H3PO4 and the molecular weight is 1989.09.
ORBACTIV is supplied as a sterile white to off-white lyophilized powder for intravenous infusion that contains oritavancin diphosphate, mannitol (an inactive ingredient) and phosphoric acid (to adjust pH 3.1 to 4.3). Each 50 ml capacity glass vial contains 449 mg oritavancin diphosphate (equivalent to 405 mg of oritavancin, 5 mg excess is to ensure withdrawal of 400 mg oritavancin), 400 mg oritavancin (free base equivalent).
Each vial is reconstituted with sterile water for injection and further diluted with 5% Dextrose in sterile Water for intravenous infusion. Both the reconstituted solution and the diluted solution for infusion should be clear, colorless to pale yellow solution.
CLINICAL PHARMACOLOGY:
Mechanism of Action:
Oritavancin has three mechanisms of action: (i) inhibition of the transglycosylation (polymerization) step of cell wall biosynthesis by binding to the stem peptide of peptidoglycan precursors; (ii) inhibition of the transpeptidation (crosslinking) step of cell wall biosynthesis by binding to the peptide bridging segments of the cell wall; and (iii) disruption of bacterial membrane integrity, leading to depolarization, permeabilization, and cell death. These multiple mechanisms contribute to the concentration-dependent bactericidal activity of oritavancin.
INDICATIONS AND USAGE
INDICATIONS AND USAGE:
Acute Bacterial Skin and Skin Structure Infections
ORBACTIV™ (Oritavancin) for injection is indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms:
Staphylococcus aureus (including methicillin-susceptible and methicillin–resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus), and Enterococcus faecalis (vancomycin-susceptible isolates only).
Usage
To reduce the development of drug-resistant bacteria and maintain the effectiveness of ORBACTIV and other antibacterial drugs, ORBACTIV should be used only to treat 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.
CONTRAINDICATIONS
Contraindications:
Intravenous Unfractionated Heparin Sodium
Use of intravenous unfractionated heparin sodium is contraindicated for 48 hours after ORBACTIV administration because the activated partial thromboplastin time (aPTT) test results are expected to remain falsely elevated for approximately 48 hours after ORBACTIV administration.
Hypersensitivity
ORBACTIV is contraindicated in patients with known hypersensitivity to ORBACTIV.
PRECAUTIONS
WARNINGS AND PRECAUTIONS:
Concomitant warfarin use: Co-administration of ORBACTIV and warfarin may result in higher exposure of warfarin, which may increase the risk of bleeding. Use ORBACTIV in patients on chronic warfarin therapy only when the benefits can be expected to outweigh the risk of bleeding.
Coagulation test interference: ORBACTIV has been shown to artificially prolong aPTT for up to 48 hours, and may prolong PT and INR for up to 24 hours.
Hypersensitivity reactions have been reported with the use of antibacterial agents including ORBACTIV. Discontinue infusion if signs of acute hypersensitivity occur. Monitor closely patients with known hypersensitivity to glycopeptides.
Infusion-related reactions have been reported. Slow the rate or interrupt infusion if infusion reaction develops.
Clostridium difficile-associated colitis: eva luate patients if diarrhea occurs.
Osteomyelitis: Institute appropriate alternate antibacterial therapy in patients with confirmed or suspected osteomyelitis.
ADVERSE REACTIONS  top of page
ADVERSE REACTIONS:
The most common adverse reactions (>/= 3%) in patients treated with ORBACTIV were headache, nausea, vomiting, limb and subcutaneous abscesses, and diarrhea.
To report SUSPECTED ADVERSE REACTIONS, contact The Medicines Company at 1-888-977-6326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.
DOSAGE AND ADMINISTRATION
DOSAGE AND AMINISTRATION:
Recommended Dosage
The recommended dosing for ORBACTIV is a single 1200 mg dose administered by intravenous infusion over 3 hours in patients 18 years and older.
Preparation of ORBACTIV for Intravenous Infusion
ORBACTIV is intended for intravenous infusion, only after reconstitution and dilution.
Three ORBACTIV 400 mg vials need to be reconstituted and diluted to prepare a single 1200 mg intravenous dose.
Reconstitution: Aseptic technique should be used to reconstitute three ORBACTIV 400 mg vials.
Add 40 mL of sterile water for injection (WFI) to reconstitute each vial to provide a 10 mg/mL solution per vial.
For each vial, gently swirl to avoid foaming and ensure that all ORBACTIV powder is completely reconstituted in solution.  Each vial should be inspected visually for particulate matter after reconstitution and should appear to be clear, colorless to pale yellow solution.
Dilution: Use ONLY 5% dextrose in sterile water (D5W) for dilution. Do NOT use Normal Saline for dilution as it is incompatible with ORBACTIV and may cause precipitation of the drug. Use aseptic technique to:
Withdraw and discard 120 mL from a 1000 mL intravenous bag of D5W.
Withdraw 40 mL from each of the three reconstituted vials and add to D5W intravenous bag to bring the bag volume to 1000 mL. This yields a concentration of 1.2 mg/mL.
Since no preservative or bacteriostatic agent is present in this product, aseptic technique must be used in preparing the final intravenous solution.
Diluted intravenous solution in an infusion bag should be used within 6 hours when stored at room temperature, or used within 12 hours when refrigerated at 2 to 8°C (36 to 46°F). The combined storage time (reconstituted solution in the vial and diluted solution in the bag) and 3 hour infusion time should not exceed 6 hours at room temperature or 12 hours if refrigerated.
Incompatibilities
ORBACTIV is administered intravenously. ORBACTIV should only be diluted in D5W. Do NOT use normal saline for dilution as it is incompatible with ORBACTIV and may cause precipitation of the drug. Therefore other intravenous substances, additives or other medications mixed in normal saline should not be added to ORBACTIV single-use vials or infused simultaneously through the same IV line or through a common intravenous port. In addition, drugs formulated at a basic or neutral pH may be incompatible with ORBACTIV. ORBACTIV should not be administered simultaneously with commonly used intravenous drugs through a common intravenous port. If the same intravenous line is used for sequential infusion of additional medications, the line should be flushed before and after infusion of ORBACTIV with D5W.
HOW SUPPLIED
DOSAGE FORMS AND STRENGTHS:
ORBACTIV is supplied as sterile, white to off-white lyophilized powder equivalent to 400 mg of oritavancin in a single use 50 mL clear glass vial.
Storage and Stability
Stability: Diluted intravenous solution in an infusion bag should be used within 6 hours when stored at room temperature, or used within 12 hours when refrigerated at 2 to 8°C (36 to 46°F). The combined storage time (reconstituted solution in the vial and diluted solution in the bag) and 3 hour infusion time should not exceed 6 hours at room temperature or 12 hours if refrigerated.
HOW SUPPLIED/STORAGE AND HANDLING
How Supplied/Storage
ORBACTIV is supplied as single use 50 mL capacity glass vials containing sterile lyophilized powder equivalent to 400 mg of oritavancin (NDC 65293-015-01). Three vials are packaged in a carton to supply for a single 1200 mg dose treatment (NDC 65293-015-03).
ORBACTIV vials should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=085d6d1a-21c2-11e4-8c21-0800200c9a66