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新型口服抗血凝药Savaysa(edoxaban)获美国FDA批准上市，用于降低非心脏瓣膜问题引起的房颤患者的中风及危险血栓风险（全身性栓塞）。
FDA的药品评价和研究中心心血管和肾产品部主任Norman Stockbridge，M.D.，Ph.D.说：“在有心房纤颤患者中，抗-凝药通过预防心脏中血凝块形成降低卒中的风险，”“对于患者重要的是有这些各种类型药物可供选择。”
批准日期：2015年1月8日 公司：第一三共制药制造
SAVAYSA（依度沙班 edoxaban）片 供口服用片剂
最初美国批准：2015年
警告在非瓣膜性房颤患者
（A）药效降低肌酐清除率（CrCl）> 95毫升/分钟
（B）SAVAYSA提前终止增加缺血事件的风险
（C）脊髓/硬膜外血肿
请参阅完整的黑框警告的完整处方信息。
（a）降低疗效非瓣膜性房颤患者与CRCL> 95毫升/分钟：SAVAYSA不应该的患者肌酐清除率> 95毫升/分钟使用。在ENGAGE AF-TIMI 48研究中，非瓣膜性房颤患者的肌酐清除率> 95毫升/分钟有缺血性中风与SAVAYSA 60毫克，每天一次增加的速度相比，与华法林治疗的患者。在这些患者中另一个抗凝剂应使用。
SAVAYSA提前终止增加缺血事件的风险：
在没有适当的替代抗凝任何口服抗凝提前终止增加缺血事件的风险。如果SAVAYSA停产超过病变出血或治疗的课程完成以外的原因，因为在过渡指导所描述考虑覆盖与另一抗凝剂。
（C）脊髓/硬膜外血肿：硬膜外或脊髓血肿可与谁正在接受椎管内麻醉或脊髓进行穿刺SAVAYSA治疗的患者发生。这些血肿可能导致长期或永久性瘫痪。调度患者脊柱程序时，请考虑这些风险。
作用机理
Edoxaban是的FXa的选择性抑制剂。它不需要抗凝血酶III为抗血栓形成活性。 Edoxaban抑制游离的FXa和凝血酶原酶的活性，并抑制凝血酶诱导的血小板聚集。在凝血级联的FXa的抑制减少了凝血酶生成，并减少血栓的形成。
适应症和用法
SAVAYSA是Xa因子抑制剂表示：
为了减少卒中和全身性栓塞（SE）的风险患者的非瓣膜性房颤（NVAF）。
使用限制的非瓣膜性房颤
SAVAYSA不应患者肌酸酐清除率（CrCl）被用来>由于缺血性中风的风险增加相比在最高剂量的华法林95毫升/分钟的研究（60毫克）。
SAVAYSA表示为以下5至10天的初始治疗的与胃肠抗凝深静脉血栓（DVT）和肺栓塞（PE）的处理。
用法用量
非瓣膜性房颤的处理：
开始治疗前评估肌酐清除率。
推荐的剂量为60毫克，每天一次患者CRCL> 50至≤95毫升/分钟。不要在患者的肌酐清除率> 95毫升/分钟使用SAVAYSA。
患者每日一次降低剂量至30mg肌酐清除率15至50毫升/分钟。
DVT和PE的处理：
推荐的剂量为60毫克，每天一次。
推荐的剂量为30毫克，每天一次患者CRCL 15至50毫升/分钟或体重小于或等于60千克或谁使用某些的P-gp抑制剂。
剂型和规格
片剂：60毫克，30毫克和15毫克。
禁忌症
主动病理出血。
警告和注意事项
出血：严重和潜在致命性出血。及时评估体征及失血症状。
机械心脏瓣膜或中度至重度二尖瓣狭窄：不推荐使用。
不良反应
非瓣膜性房颤的治疗：最常见的不良反应（≥5％）是出血和贫血。
DVT和PE的处理：最常见的不良反应（≥1％）有出血，皮疹，肝功能异常和贫血。
药物相互作用
抗凝血剂：
避免同时使用。
利福平：
避免同时使用。
特殊人群中使用
哺乳母亲：请停止药物或停止哺乳。
肾功能受损（肌酐清除率15〜50毫升/分钟）：减少剂量。
中度或重度肝功能损害：不推荐。
Savaysa (edoxaban tosylate) 15, 30, and 60mg tablets Description:
FDA approved(First approved January 8th, 2015)
Brand name: Savaysa
Generic name: edoxaban
Company: Daiichi Sankyo
Treatment for: Prevention of Thromboembolism in Atrial Fibrillation, Deep Vein Thrombosis, Pulmonary Embolism
Savaysa (edoxaban) is an oral, once-daily factor Xa inhibitor anticoagulant indicated for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, and for the treatment of deep vein thrombosis, and pulmonary embolism.
SAVAYSA Rx
Pharmacological Class:
Factor Xa inhibitor.
Active Ingredient(s):
Edoxaban 15mg, 30mg, 60mg; tablets.
Company
Daiichi Sankyo
Indication(s):
To reduce the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF). Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5–10 days of initial therapy with parenteral anticoagulant. Limitations of use: not for use in NVAF patients with CrCl >95mL/min.
Pharmacology:
Edoxaban is a selective inhibitor of FXa. It does not require antithrombin III for antithrombotic activity. Edoxaban inhibits free FXa, and prothrombinase activity and inhibits thrombin-induced platelet aggregation. Inhibition of FXa in the coagulation cascade reduces thrombin generation and reduces thrombus formation.
Clinical Trials:
The safety and efficacy of Savaysa was compared to warfarin in ENGAGE AF-TIMI 48, a multi-national, double-blind, non-inferiority study in reducing the risk of stroke and systemic embolic events (SEE) in patients with NVAF. A total of 21,105 patients were randomized to Savaysa 30mg, Savaysa 60mg, or warfarin. The primary endpoint of the study was the occurrence of first stroke (ischemic or hemorrhagic) or SEE that occurred during treatment or within 3 days from the last dose taken. Study results showed both Savaysa treatment arms were non-inferior to warfarin for the primary efficacy endpoint. However, the Savaysa 30mg treatment arm was found to be less effective vs. warfarin for the primary endpoint and was also inferior in reducing the rate of ischemic stroke. Treatment with Savaysa 60mg had a lower incidence of first stroke or SEE vs. warfarin (HR 0.79; [97.5% CI: 0.63, 0.99]; P=0.017).
In the Hokusai-VTE study population, Savaysa 60mg once daily showed to be non-inferior to warfarin for the primary efficacy endpoint of recurrence of symptomatic venous thromboembolism (3.2% vs. 3.5%; HR 0.89; [95% CI: 0.70, 1.13]).
For more clinical trials data, see full labeling.
Legal Classification:
Rx
Adults:
Assess CrCl prior to initiation. NVAF: CrCl >50mL/min: 60mg once daily; CrCl 15–50mL/min: 30mg once daily. DVT/PE: CrCl >50mL/min: 60mg once daily following initial parenteral anticoagulant; CrCl 15–50mL/min, body wt. ≤60kg, or concomitant P-gp inhibitors: 30mg once daily. Transition to or from Savaysa: see full labeling.
Children:
Not established.
Contraindication(s):
Active pathological bleeding.
Warnings/Precautions:
Reduced efficacy in NVAF patients with CrCl >95mL/min; use another anticoagulant. Premature discontinuation increases risk of ischemic events; if discontinued for reason other than bleeding or therapy completion, consider coverage with another anticoagulant. Increased risk of spinal/epidural hematoma in anticoagulated patients receiving neuraxial anesthesia or undergoing spinal puncture (eg, use of indwelling epidural catheters); monitor for signs/symptoms of neurological impairment. Increased risk of bleeding; monitor for signs/symptoms of blood loss; discontinue if active pathological hemorrhage occurs. Patients with mechanical heart valves or moderate-to-severe mitral stenosis: not recommended. Discontinue 24 hours before surgery. Renal impairment (CrCl <15mL/min), moderate or severe hepatic impairment (Child-Pugh B and C): not recommended. Labor & delivery. Pregnancy (Category C). Nursing mothers: not recommended.
Interaction(s)
Increased risk of bleeding with concomitant aspirin, antiplatelet drugs, other antithrombotic agents, fibrinolytic therapy, NSAIDs; monitor. Concomitant other anticoagulants in long term therapy: not recommended. Avoid concomitant P-gp inducers (eg, rifampin).
Adverse Reaction(s)
Bleeding (may be serious or fatal), anemia, rash, abnormal LFTs.
How Supplied:
Tabs 15mg—30; 30mg, 60mg—30, 90, 500
LAST UPDATED:
4/2/2015
http://www.drugs.com/pro/savaysa.html
http://www.fda.gov/Drugs/InformationOnDrugs/ucm428735.htm |
