近日，美国FDA批准Andexxa（凝血因子Xa(重组)，inactivated-zhzo）作为首个及唯一一个凝血因子Xa抑制剂（利伐沙班、阿哌沙班）的解毒药物，用于当出现危及生命或无控制出血后的抗凝的逆转。
Andexxa是一种重组蛋白，可特异性结合Xa因子抑制剂并快速逆转其抗凝作用。Andexxa是经修饰的人凝血因Xa，高特异性的竞争结合口服和注射型的Xa因子抑制剂。
批准日期：2018年5月3日 公司：Portola制药
ANDEXXA（凝血因子Xa(重组)，inactivated-zhzo）冻干粉末，用于静脉注射溶液
美国最初批准：2018年
警告：
血栓形成风险，缺血风险，
CARDIAC ARREST和SUDDEN DEATHS
查看完整的盒装警告的完整处方信息使用ANDEXXA治疗与严重和危及生命的不良事件有关，包括：
•动脉和静脉血栓栓塞事件
•缺血性事件，包括心肌梗塞和缺血性中风
• 心脏骤停
•突然死亡
监测血栓栓塞事件并在医学上适当时启动抗凝治疗。监测心脏骤停前的症状和体征，并根据需要提供治疗。
作用机制
通过结合和隔离FXa抑制剂，利伐沙班和阿哌沙班来发挥其促凝血作用。 另一种观察到的ANDEXXA蛋白的促凝血作用是其结合和抑制组织因子途径抑制剂（TFPI）活性的能力。
抑制TFPI活性可以增加组织因子引发的凝血酶产生。
适应症和用法
适用于用利伐沙班和阿哌沙班治疗的患者，当由于危及生命或不受控制的出血而需要逆转抗凝时。
基于健康志愿者中抗FXa活性的基线变化，该指示在加速批准下被批准。尚未确定止血的改善。
该指征的持续批准可能取决于研究结果，以证明患者止血的改善。
使用限制
对于与阿哌沙班和利伐沙班除外的任何FXa抑制剂相关的出血的治疗，ANDEXXA未被证明是有效的，并且不适用于治疗。
剂量和给药
仅限静脉注射。
•剂量ANDEXXA基于特定的FXa抑制剂，FXainhibitor的剂量，以及自患者最后一剂FXa抑制剂以来的时间。
•作为静脉注射（IV）推注，目标速率为30mg/min，然后连续输注最多120分钟。
•有两种给药方案：
  剂量                           初始IV Bolus                      后续IV输注
低剂量:400mg，目标速率为30mg/min，4mg/min， 持续120分钟
高剂量：800mg，目标速率为30mg/min，8mg/min，持续120分钟
*多种剂量的安全性和有效性尚未得到评估。
剂量形式和强度
ANDEXXA可作为冻干粉末在100mg凝血因子Xa（重组）的一次性小瓶中使用，灭活的zhzo。
禁忌症
没有。
警告和注意事项
•使用ANDEXXA治疗期间发生了动脉和静脉血栓栓塞事件，缺血事件和心脏病，包括猝死。在用ANDEXXA治疗后，在医学上适当时立即恢复抗凝治疗。
•可能发生抗凝血活性的再升高或不完全逆转。
不良反应
接受ANDEXXA治疗的患者最常见的不良反应（≥5％）是尿路感染和肺炎。
使用ANDEXXA治疗的健康志愿者中最常见的不良反应（≥3％）是输注相关反应。
包装提供/存储和处理
提供
ANDEXXA以4个一次性小瓶的纸盒供应，每个小瓶含有100毫克ANDEXXA，白色至灰白色冻干饼或粉末。
NDC 69853-0101-1
存储和处理
未开封的小瓶应在2°C至8°C（36°F至46°F）的温度下冷藏。 不要冻结。

完整资料附件：
https://www.andexxa.com/wp-content/uploads/Andexxa%20USPI-v1.4-may2018.pdf
Andexxa(Coagulation Factor Xa (recombinant), Inactivated-zhzo for Injection)
INDICATION AND SELECT IMPORTANT SAFETY INFORMATION
WARNING: THROMBOEMBOLIC RISKS, ISCHEMIC RISKS, CARDIAC ARREST, AND SUDDEN DEATHS
See full prescribing information for complete boxed warning
Treatment with ANDEXXA has been associated with serious and life‑threatening adverse events, including:
Arterial and venous thromboembolic events
Ischemic events, including myocardial infarction and ischemic stroke
Cardiac arrest
Sudden deaths
Monitor for thromboembolic events and initiate anticoagulation when medically appropriate. Monitor for symptoms and signs that precede cardiac arrest and provide treatment as needed.
Indication
ANDEXXA, coagulation factor Xa (recombinant), inactivated-zhzo is indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.
This indication is approved under accelerated approval based on the change from baseline in anti-FXa activity in healthy volunteers. An improvement in hemostasis has not been established. Continued approval for this indication may be contingent upon the results of studies to demonstrate an improvement in hemostasis.
Limitation of Use:
ANDEXXA has not been shown to be effective for, and is not indicated for, the treatment of bleeding related to any FXa inhibitors other than apixaban and rivaroxaban.
SELECT IMPORTANT SAFETY INFORMATION
Thromboembolic Risk
Arterial and venous thromboembolic events, ischemic events, sudden deaths, or events where a thrombotic event could not be ruled out were observed within 30 days post-ANDEXXA administration in 33 of the 185 patients (17.8%) evaluable for safety in the ongoing ANNEXA-4 study. The median time to these events was 6 days. Of the 86 patients who were re-anticoagulated prior to a thrombotic event, 11 (12.7%) patients experienced a thromboembolic, ischemic event, cardiac event or death.
Monitor patients treated with ANDEXXA for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. To reduce thromboembolic risk, resume anticoagulant therapy as soon as medically appropriate following treatment with ANDEXXA.
The safety of ANDEXXA has not been evaluated in patients who experienced thromboembolic events or disseminated intravascular coagulation within two weeks prior to the life-threatening bleeding event requiring treatment with ANDEXXA. Safety of ANDEXXA also has not been evaluated in patients who received prothrombin complex concentrates, recombinant factor VIIa, or whole blood products within seven days prior to the bleeding event.
Re-elevation or Incomplete Reversal of Anti-FXa Activity
The time course of anti-FXa activity following ANDEXXA administration was consistent among the healthy volunteer studies and the ANNEXA-4 study in bleeding patients. Compared to baseline, there was a rapid and substantial decrease in anti-FXa activity corresponding to the ANDEXXA bolus. This decrease was sustained through the end of the ANDEXXA continuous infusion. Following the infusion, there was an increase in anti-FXa activity, which peaked 4 hours after infusion in ANNEXA-4 subjects. After this peak, the anti-FXa activity decreased at a rate similar to the clearance of the FXa inhibitors.
Thirty-eight patients who were anticoagulated with apixaban had baseline levels of anti-FXa activity >150 ng/mL. Nineteen of these 38 (50%) patients experienced a > 93% decrease from baseline anti-FXa activity after administration of ANDEXXA. Eleven patients who were anticoagulated with rivaroxaban had baseline anti-FXa activity levels > 300 ng/mL. Five of the 11 patients experienced a >90% decrease from baseline anti-FXa activity after administration of ANDEXXA.
Adverse Reactions
The most common adverse reactions (≥ 5%) in patients receiving ANDEXXA were urinary tract infections and pneumonia.
The most common adverse reactions (≥ 3%) in healthy volunteers treated with ANDEXXA were infusion-related reactions.
Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. Low titers of anti-ANDEXXA antibodies were observed in 26/145 healthy subjects (17%); 6% (9/145) were first observed at Day 30 with 20 subjects (14%) still having titers at the last time point (days 44 to 48). To date, the pattern of antibody response in patients in the ANNEXA-4 study has been similar to that observed in healthy volunteers with 6% of the patients having antibodies against ANDEXXA (6/98 patients). None of these anti-ANDEXXA antibodies were neutralizing. No antibodies cross-reacting with FX or FXa were detected in healthy subjects (0/145) or in bleeding patients to date (0/98).
https://www.andexxa.com/how-andexxa-is-supplied/