近日，美国FDA批准TNK酶剂Activase（alteplase recombinant，阿替普酶）冻干粉注射剂，是一个重组组织型纤维蛋白溶酶原激活物(tPa),可以溶解严重心肌梗塞患者的血块。也被用来治疗非出血型中风。
批准日期：2001年09月04日 公司：基因技术公司
Activase（阿替普酶/活化酶[alteplase recombinant]）注射，静脉内使用
美国初次批准：1987年
最近的重大变化
警告和注意事项：02/2018
作用机理
阿替普酶是一种丝氨酸蛋白酶，负责将纤维蛋白溶酶原转化为纤溶酶。
在没有纤维蛋白的情况下，它会产生纤溶酶原的有限转化。
当以药理学浓度引入全身循环时，阿替普酶与血栓中的血纤蛋白结合，并将捕获的纤溶酶原转化为纤溶酶。 这会启动局限性蛋白水解，而全身蛋白水解受限。
适应症和用途
激活酶是一种组织纤溶酶原激活剂（tPA），可用于治疗
•急性缺血性中风（AIS）。
•急性心肌梗塞（AMI）以降低死亡率和心力衰竭的发生率。
在AMI中使用的局限性：中风的风险可能大于因心脏原因死亡的低风险患者的获益。
•急性大量肺栓塞（PE）用于裂解。
剂量和给药
•急性缺血性中风：建议剂量为0.9mg/kg（不超过90mg总剂量），在60分钟内静脉输注，并在1分钟内以总剂量的10％进行初始推注。
•急性心肌梗塞：建议的总剂量基于患者的体重，不超过100mg。
•急性大量肺栓塞：推荐剂量为100毫克，在2小时内静脉输注。
•请勿在含激活酶的输液中添加其他药物。
剂量形式和强度
•冻干粉剂：50mg和100mg注射用无菌水，每1mL 1mg复溶。
禁忌症
一般
•活动性内出血。
•最近的颅内或脊柱内手术或严重的头部外伤。
•颅内疾病可能会增加出血的风险。
•出血素质。
•当前严重的无法控制的高血压。
急性缺血性中风
•当前的颅内出血。
• 蛛网膜下腔出血。
急性心肌梗塞或肺栓塞
•最近的中风病史。
警告和注意事项
•增加出血的风险。避免肌肉注射。监控出血。如果发生严重的出血，请停止激活酶。
•在输液过程中以及输注后的几个小时内监测患者的超敏反应。如果出现超敏反应迹象，请停止激活酶。
•考虑肺栓塞患者潜在的深层静脉血栓溶解导致再次栓塞的风险。
•很少有溶栓剂治疗的患者发生胆固醇栓塞。
不良反应
最常见的不良反应（> 5％）是出血。
要报告可疑的不良反应，请致电1-888-835-2555与Genentech联系，或致电1-800-FDA-1088与FDA联系或访问www.fda.gov/medwatch。
药物相互作用
•给予激活酶治疗时，抗凝药和抑制血小板功能的药物会增加出血的风险。
•伴随的血管紧张素转换酶抑制剂可能会增加血管性水肿的风险。
包装供应/存储和处理方式
供应方式
活化酶以无菌，冻干的粉末形式提供，含50mg含真空的小瓶和100mg无真空的小瓶。
每个50毫克 Activase小瓶（2900万IU）与稀释剂一起包装以进行重建（50毫升注射用无菌水，USP）：NDC 50242-044-13。
每个100毫克Activase小瓶（5800万IU）包装有用于重建的稀释剂（100毫升无菌注射用水，USP）和一个转移装置：NDC 50242-085-27。
稳定性和储存
将冻干的活化酶保存在室温下，不要超过30°C（86°F）或冷藏不足（2-8°C/36-46°F）。延长储存时间，防止冻干的材料过度暴露于光下。如果储存在2-30°C（36-86°F）之间，则可在重组后8小时内使用Activase。 管理完成后，请丢弃所有未使用的解决方案。
请勿在小瓶上标明的失效日期后使用。
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ACTIVASE 50MG VL  ALTEPLASE  GENENTECH INC. USA NDC：50242004413
ACTIVASE 100MG VL  ALTEPLASE  GENENTECH INC. USA  NDC：50242008527
ACTIVASE 100MG SDV PWD 1/EA  ALTEPLASE RECOMBINANT  GENENTECH INC.  NDC：50242-0085-27
ACTIVASE 50MG SDV PWD W/DIL 1/EA  ALTEPLASE RECOMBINANT GENENTECH INC. NDC：50242-0044-13
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Activase (alteplase) for injection, for intravenous use
Initial U.S. Approval: 1987
Important Safety Information & Indication
Important Safety Information
Contraindications
Do not administer Activase to treat acute ischemic stroke in the following situations in which the risk of bleeding is greater than the potential benefit: current intracranial hemorrhage (ICH); subarachnoid hemorrhage; active internal bleeding; recent (within 3 months) intracranial or intraspinal surgery or serious head trauma; presence of intracranial conditions that may increase the risk of bleeding (e.g., some neoplasms, arteriovenous malformations, or aneurysms); bleeding diathesis; and current severe uncontrolled hypertension.
Do not administer Activase to treat acute myocardial infarction or pulmonary embolism in the following situations in which the risk of bleeding is greater than the potential benefit: active internal bleeding; history of recent stroke; recent (within 3 months) intracranial or intraspinal surgery or serious head trauma; presence of intracranial conditions that may increase the risk of bleeding; bleeding diathesis; and current severe uncontrolled hypertension.
Warnings and Precautions
Bleeding
Activase can cause significant, sometimes fatal internal or external bleeding, especially at arterial and venous puncture sites. Avoid intramuscular injections and trauma to the patient. Perform venipunctures carefully and only as required. Fatal cases of hemorrhage associated with traumatic intubation in patients administered Activase have been reported. Aspirin and heparin have been administered concomitantly with and following infusion with Activase in the management of acute myocardial infarction and pulmonary embolism. The concomitant administration of heparin and aspirin with and following infusions of Activase for the treatment of acute ischemic stroke during the first 24 hours after symptom onset has not been investigated. Because heparin, aspirin, or Activase may cause bleeding complications, carefully monitor for bleeding, especially at arterial puncture sites. Hemorrhage can occur 1 or more days after administration of Activase, while patients are still receiving anticoagulant therapy. If serious bleeding occurs, terminate the Activase infusion, and treat appropriately.
In the following conditions, the risks of bleeding with Activase are increased and should be weighed against the anticipated benefits: recent major surgery or procedure; cerebrovascular disease; recent intracranial hemorrhage; recent gastrointestinal or genitourinary bleeding; recent trauma; hypertension; acute pericarditis; subacute bacterial endocarditis; hemostatic defects including those secondary to severe hepatic or renal disease; significant hepatic dysfunction; pregnancy; diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions; septic thrombophlebitis or occluded AV cannula at seriously infected site; advanced age; and patients currently receiving oral anticoagulants, or any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location.
Hypersensitivity
Hypersensitivity, including urticarial/anaphylactic reactions, have been reported after administration of Activase. Rare fatal outcome for hypersensitivity was reported. Angioedema has been observed during and up to 2hours after Activase infusion in patients treated for acute ischemic stroke and acute myocardial infarction. In many cases, patients received concomitant angiotensin-converting enzyme inhibitors. Monitor patients treated with Activase during and for several hours after infusion for hypersensitivity.If signs of hypersensitivity occur, e.g. anaphylactoid reaction or angioedema develops, discontinue the Activase infusion and promptly institute appropriate therapy(e.g., antihistamines, intravenous corticosteroids, epinephrine).
Thromboembolism
The use of thrombolytics can increase the risk of thrombo-embolic events in patients with high likelihood of left heart thrombus, such as patients with mitral stenosis or atrial fibrillation. Activase has not been shown to treat adequately underlying deep vein thrombosis in patients with PE. Consider the possible risk of re-embolization due to the lysis of underlying deep venous thrombi in this setting.
Cholesterol Embolization
Cholesterol embolism, sometimes fatal, has been reported rarely in patients treated with thrombolytic agents; the true incidence is unknown. It is associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy.
Coagulation Tests May be Unreliable during Activase Therapy
Coagulation tests and/or measures of fibrinolytic activity may be unreliable during Activase therapy unless specific precautions are taken to prevent in vitro artifacts. When present in blood at pharmacologic concentrations, Activase remains active under in vitro conditions, which can result in degradation of fibrinogen in blood samples removed for analysis.
Adverse Reactions
The most frequent adverse reaction associated with Activase therapy is bleeding.
1)https://www.gene.com/download/pdf/activase_prescribing.pdf
2)https://www.activase.com/ais/dosing-and-administration/reconstituting.html