新型抗凝剂Praxbind(idarucizumab)注射溶液为第一个逆转剂获美国FDA批准上市
—Praxbind(idarucizumab)批准为特异性紧急情况
近期，美国食品药品监督管理局FDA批准泰毕全®（达比加群酯）的特异性逆转剂Praxbind®(idarucizumab)。Praxbind®获批用于接受泰毕全®（达比加群酯）治疗的患者，在急诊手术、介入性操作、或者出现危及生命或无法控制的出血并发症，需要逆转达比加群酯的抗凝效应时使用。
FDA药品评价和研究中心血液学和肿瘤产品室主任Richard Pazdur，M.D.说：“Pradaxa的抗凝剂作用对有些患者是重要和挽救生命，但其中也有情况逆转药物作用是医疗上必要的，” “今天的批准为医学社会提供一个重要工具为在紧急或危及生命情况当出血不能控制时处理用Pradaxa。” 加快批准程序
批准日期：2015年10月16日；公司：Boehringer Ingelheim Pharmaceuticals，Inc.
PRAXBIND(达比加群酯 idarucizumab)注射液，供静脉使用
美国初次批准：2015
作用机制
Idarucizumab是一个对达比加群特异性逆转剂。它是一个人源化单克隆抗体片段(Fab)与达比加群及其酰基葡萄糖醛酸苷代谢物结合亲和力比达比加群与凝血酶的结合亲和力有更高，中和它们的抗凝剂效应。
适应证和用途
PRAXBIND是一个人源化单克隆抗体片段(Fab)适用在用Pradaxa®当患者需要逆转达比加群[dabigatran]的抗凝剂效应治疗时：
⑴为急诊手术/紧急程序
⑵在危及生命或不能控制出血
这个适应证是在加快批准下被批准根据在健康志愿者非结合的达比加群和归一化凝固参数的减低。继续批准这个适应证可能取决于正在进行队列病例系列研究的结果。
剂量和给药方法
只为静脉使用。
⑴PRAXBIND的推荐剂量是5g，以分开2小瓶各含2.5g/50mL idarucizumab提供。
⑵有限数据支持给予另外5g的PRAXBIND。
剂型和规格
注射液：在一次性使用小瓶中2.5g/50mL溶液
禁忌证
无。
警告和注意事项
血栓栓塞风险：达比加群治疗暴露患者于他们所患疾病的血栓形成的风险的逆转。医疗上适当立即恢复抗凝剂治疗。
凝固参数的再升高：In患者有升高的凝固参数和临床上相关出血的再出现或需要一个第二次急诊手术/紧急程序，可能被考虑另外5g剂量PRAXBIND。
超敏性反应：终止给药和评价。
在由于敷料山梨醇有遗传学果糖不能耐受患者严重不良反应的风险:有遗传性果糖不能耐受患者可能是处于不良反应的风险。
不良反应
在健康志愿者中，用idarucizumab治疗受试者最常报道大于或等于5%不良反应是头痛。
在患者，用idarucizumab治疗患者最常报道大于或等于5%不良反应是低钾血症，谵妄，便秘，发热，和肺炎
供应/贮存和处置
供应
● PRAXBIND是一个无菌，无防腐剂，无色至浅黄色，清澈至略微乳白色溶液在2个一次性小瓶中供应，各含2.5g/50mL的idarucizumab。
●NDC号0597-0197-05：纸盒含2个2.5g/50mL小瓶。
贮存和处置
●贮存PRAXBIND小瓶在冰箱在2ºC至8ºC(36ºF至46ºF)。不要冻结。不要摇晃。
●使用前，未打开小瓶可保持在室温25°C(77°F)共至48小时，如贮存在原包装为了避光保护，或至6小时当暴露于光。

IMPORTANT SAFETY INFORMATION AND INDICATION FOR PRAXBIND
WARNINGS AND PRECAUTIONS
Thromboembolic Risk
Dabigatran-treated patients have underlying diseases predisposing them to thromboembolic events. Reversing dabigatran therapy exposes patients to the thrombotic risk of their underlying disease. To reduce this risk, resumption of anticoagulant therapy should be considered as soon as medically appropriate.
Re-elevation of Coagulation Parameters
Elevated coagulation parameters (e.g., activated partial thromboplastin time or ecarin clotting time) have been observed in a limited number of PRAXBIND-treated patients. If reappearance of clinically relevant bleeding together with elevated coagulation parameters is observed or if patients requiring a second emergency surgery/urgent procedure have elevated coagulation parameters, an additional full dose may be considered.
Hypersensitivity Reactions
There is insufficient clinical experience evaluating risk of hypersensitivity to idarucizumab, but a possible relationship could not be excluded. Risk of hypersensitivity (e.g., anaphylactoid reaction) to idarucizumab or excipients needs to be weighed cautiously against the potential benefit. If serious allergic reaction occurs, immediately discontinue PRAXBIND and institute appropriate treatment.
Risk in Patients with Hereditary Fructose Intolerance
PRAXBIND contains 4 g sorbitol as an excipient. When prescribing PRAXBIND in patients with hereditary fructose intolerance consider the total daily amount of sorbitol/fructose consumption from all sources as serious adverse reactions (e.g. hypoglycemia, hypophosphatemia, metabolic acidosis, increase in uric acid, acute liver failure and death) may occur.
ADVERSE REACTIONS
The most frequently reported adverse reaction in ≥5% of idarucizumab-treated healthy volunteers was headache (12/224). The most frequently reported adverse reactions in ≥5% of patients were hypokalemia (9/123), delirium (9/123), constipation (8/123), pyrexia (7/123) and pneumonia (7/123).
As with all proteins there is a potential for immunogenicity with idarucizumab. In treated patients, treatment-emergent antibodies with low titers were observed (9/224).
USE IN SPECIFIC POPULATIONS
Pregnancy and Nursing Mothers
PRAXBIND should be given to a pregnant or nursing woman only if clearly needed.
INDICATIONS AND USAGE
PRAXBIND is indicated in patients treated with Pradaxa® when reversal of the anticoagulant effects of dabigatran is needed:
For emergency surgery/urgent procedures
In life-threatening or uncontrolled bleeding
This indication is approved under accelerated approval based on a reduction in unbound dabigatran and normalization of coagulation parameters in healthy volunteers. Continued approval for this indication may be contingent upon the results of an ongoing cohort case series study.
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7400f8a-dcf4-a6df-6d07-983081b1bf34