部份中文阿加曲班处方资料（仅供参考） 阿加曲班（Argatroban）是一种活性强、高度选择性、完全可逆的凝血酶抑制剂 ，极低浓度时即可抑制由凝血酶诱导的血小板凝聚反应，其分子量小 ，它能进入到血栓内部， 直接灭活已经与纤维蛋白血栓结合的凝血酶 ，对那些陈旧的血栓仍能发挥抗栓作用。用于对下肢动脉血栓栓塞性疾病、脑血栓、急性心梗溶栓、PCI后预防再闭塞、HIT病人血栓形成的预防和治疗、用于HIT病人进行大和小的外周血管手术，是安全性高、适用广泛的抗血栓药物。 药品英文名 Argatroban 药品别名 阿戈托班  阿加曲班  ARGATROBAN HYDRATE  NOVASTAN 药物剂型 注射剂(供输注用)：250mg(2.5ml)。 药理作用 本品为合成的左旋精氨酸的哌啶羧酸衍生物，属于抗凝药。是由R-和S-同分异构体按65%和35%的比例组合而成。S-同分异构体抑制凝血酶的活力为R-同分异构体的2倍。本品为小分子物质，具有高选择性，能可逆性直接抑制凝血酶的活性。能迅速和循环中游离的和与血凝块中的凝血酶结合，产生抗凝作用。 药动学 在静脉滴注阿加曲班每分钟40μg/kg以内，剂量与血浆浓度呈线性关系。作用出现迅速，约30min即出现。在给药2h后血浆浓度达峰值。持续静脉滴注在1～3h内血浆浓度达稳态。阿加曲班在体内分布容积是174ml/kg，主要是在细胞外分布，它的血浆蛋白结合率为54%。阿加曲班主要是在肝脏代谢，约65%被代谢为4个代谢产物。主要代谢产物的抗凝活性较原药弱3～5倍，其他3个代谢产物在尿中含量甚低，在血浆和粪中未检测出。阿加曲班主要是通过胆汁从粪便中排出，健康志愿者的清除半衰期约为40～50min。药物监测指标为APTT，控制在原水平1.5～3倍。本品进入肝内后，经羟化作用而代谢。本品不会诱导自身的抗体形成，也不会与肝素诱导的抗体发生相互作用。 适应证 用于与肝素引起血小板减少有关的血栓形成。 禁忌证 1.对本品过敏者、哺乳者禁用。 2.任何出血患者均禁用。 注意事项 1.严重高血压、腰穿术后、脊髓麻醉、大手术特别是脑、脊髓或眼科手术后、胃肠溃疡、先天或后天获得的出血性疾病均应慎用。 2.肝功能不全者使用本品时，应减少剂量并监测APTT。中度不全者，推荐剂量为每分钟0.5μg/kg。 3.老年人和肾功能不全者不必调整剂量。 4.小于18岁儿童的用药安全性尚未确定。5.输注的速度根据体重而定，体重50kg，每小时输入6ml(50/6)，余类推为(60/7)，(70/8)，(80/10)，(90/11)，(100/12)，(110/13)，(120/14)，(130/16)，(140/17)。6.在两项多中心临床试验中，对肝素诱发血小板减少症和肝素诱发伴有血栓血小板减少症的患者，静脉滴注阿加曲班每分钟2μg/kg，可较原水平延长APTT 1.5～3倍，且在停用肝素第3天约50%患者血小板可恢复，但出血不良反应与对照组无区别。孕妇及哺乳期妇女用药、儿童用药、老年患者用药和药物相互作用参见比伐卢定。药物过量，若应用阿加曲班过量，无特效药物纠正，须停用阿加曲班后2～4hAPTT和ACT恢复至原水平。 不良反应 常见的有各种不同的出血、呼吸困难、低血压、发热、腹泻、脓毒症、房室传导阻滞、恶心、室性心动过速、疼痛、尿路感染和呕吐。过敏反应的发生率为14%。以阿加曲班治疗不稳定型心绞痛患者停药后可出现心绞痛，及时给予阿司匹林可避免。 用法用量 1.本品供持续输注。给药前，先将注射剂配制成1mg/ml的溶液，稀释液采用0.9%氯化钠注射剂、5%右旋糖酐注射剂或乳酸林格液均可。配制时，要反复倒转瓶子数min，使溶液充分溶化。配制好的溶液室温上可保持稳定24h，置冰箱中可保持48h。 2.防治HIT患者的血栓形成，开始给予每分钟2μg/kg，静脉输注，同时监测ATPP。在治疗后1～3h，常可达较稳定的抗凝效果。在开始输入本品和(或)调查剂量后2h，应当测定APTT，并证实其达到靶值(1.5～3倍的基础值，但不要超过100秒钟)。根据临床调整速度时，不要＞每分钟100μg/kg。 3.在使用本品治疗后，可继续接用华法林。 4.对出现肝素诱发血小板减少的患者，应先停用肝素治疗，并测基础的APTT值，推荐剂量为首先以阿加曲班每分钟2μg/kg静脉滴注，此后根据APTT值调整剂量，最大不超过每分钟10μg/kg。对于中度肝功能不全患者，首先以阿加曲班每分钟0.5μg/kg静脉滴注，此后根据APTT值调整剂量。 药物相应作用 1.与华法林合用可能发生药动学相互作用，使凝血酶原时间延长。 2.合用其他抗凝药均可增加出血的危险性。 临床研究 本品为合成的左旋精氨酸的哌啶羧酸衍生物，属于抗凝药。为小分子物质，具有高选择性，能可逆性直接抑制凝血酶的活性。能迅速和循环中游离的与血凝块中的凝血酶结合，产生抗凝作用。用于与肝素引起血小板减少有关的血栓形成。 Novastan HI（ARGATROBAN HYDRATE） Name of drug classification Selective antithrombin agent Sales name Novastan HI Note 10mg/2 mL Property White crystal or crystalline powder, taste bitter. It is easily soluble in acetic acid (100), slightly soluble in methanol, hardly soluble in ethanol (99.5), and very insoluble in water. Decompose slowly with light. Melting point 180 - 220 ° C (decomposition) Distribution coefficient 0.031 (pH 6.0, chloroform / buffer solution) composition Active ingredient [in 1 tube (2 mL)] Japanese Agar Argatroban hydrate 10 mg Additive [in 1 tube (2 mL)] 300 mg of absolute ethanol, 900 mg of concentrated glycerin, an appropriate amount of hydrochloric acid, an appropriate amount of sodium hydroxide Contraindications Bleeding patients: intracranial haemorrhage, hemorrhagic cerebral infarction, thrombocytopenic purpura, bleeding tendency due to vascular disorders, hemophilia and other coagulopathies, during menstruation, during surgery, gastrointestinal bleeding, urinary tract hemorrhage, hemoptysis , Premature births with premature labor or immediate sexual bleeding immediately after parturition, etc. Menstrual women etc. [When hemorrhagic patients are administered, hemostasis may become difficult. (See the "Warning" section)] Patients with cerebral embolism or cerebral embolism (excluding patients with heparin-induced thrombocytopenia (HIT) type II) [May cause bleeding cerebral infarction. (See "Warning" and "Important basic attention")] Patients with major infarction with severe consciousness disturbance [Patients with major infarction can cause hemorrhagic cerebral infarction. (See the "Warning" section)] Patients with a history of hypersensitivity to this drug Indication or effect Improvement of neurologic symptoms (motor paralysis) and daily living movements (walking, standing, sitting retention, meal) associated with the following diseases Acute phase of cerebral thrombosis within 48 hours after onset (excluding racune) Normally, 6 adults per day for the first 2 days (60 mg as Argatroban hydrate) are diluted with adequate infusion solution for the first 2 days, and intravenous drip infusion is given over 24 hours. For the following 5 days, 1 tube (10 mg as Argatroban hydrate) is diluted with an appropriate amount of infusion solution and intravenously infused intravenously 2 times a day, in the morning and evening, once over 3 hours. Incidentally, it should be increased or decreased according to your age and symptoms. Improvement of extremity ulcer, resting pain and cooling sensation in chronic arterial obstruction (Buerger disease · obstructive arteriosclerosis) Usually, 1 tube per adult (10 mg as Argatroban hydrate) is diluted with infusion and intravenously infused over 2 to 3 hours once a day twice a day. Incidentally, it should be increased or decreased according to your age and symptoms. Prevention of clotting of perfused blood during extracorporeal circulation in the following patients (hemodialysis) Congenital antithrombin III deficient patients Patients with antithrombin III lowering (Those whose antithrombin III has been judged to be reduced to 70% or less of normal and blood clotting (residual blood) in the extracorporeal circulation path is not improved by using heparin sodium or heparin calcium) Heparin-induced thrombocytopenia (HIT) type II patients Usually, adults receive 1 tube (10 mg as argatroban hydrate) at the start of extracorporeal circulation in the circuit and start administration from 2.5 tubes per hour (25 mg as argatroban hydrate) after start of extracorporeal circulation. Dosage for each patient is determined by increasing or decreasing the dosage using indicators such as prolongation of coagulation time, in-circuit coagulation (residual blood), dialysis efficiency and hemostasis status at the end of dialysis, etc., but 0.5 to 4 tubes per hour (argatroban water 5-40 mg as a standard) as a guide. Prevention of clotting of blood during percutaneous coronary intervention in heparin-induced thrombocytopenia (HIT) type II (including cases of onset risk) This drug is diluted with an appropriate amount of infusion solution, usually 0.1 mg / kg as an argatroban hydrate is administered intravenously to adults over 3 to 5 minutes and up to 4 hours postoperatively, Argatroban hydrate at 6 μg / kg / Continue intravenously with a minute as a guide. If continued anticoagulation therapy is required thereafter, decrease to 0.7 μg/kg/min and continue intravenously. The continuous dosage is a standard, and it is adjusted as appropriate by monitoring appropriate coagulability. Inhibition of the onset of thrombosis in heparin-induced thrombocytopenia (HIT) type II Dilute this drug with an appropriate amount of infusion solution, usually by intravenous infusion of Argatroban hydrate at 0.7 μg /kg/min for adults and continue administration. For patients with liver dysfunction or patients with risk of bleeding, administration should be started from a low dose. The dose is increased or decreased using the activated partial thromboplastin time (aPTT) as an index, and the dose for each patient is determined. When used during extravascular blood circulation, it is desirable not to administer in patients with antithrombin III lowering due to disseminated intravascular coagulation syndrome (DIC) since they have not been administered during blood extracorporeal circulation. When used for patients with chronic arterial obstruction Since experience of dosing beyond 4 weeks is small, administration period of this drug should be within 4 weeks. When used for hemodialysis patients with antithrombin III lowering state When antithrombin III recovers to 70% or more by using this drug and it is judged that clotting (residual blood) in the extracorporeal circuit can be managed, we will promptly examine the use of heparin sodium and heparin calcium, Do not use this drug gently. When used to prevent coagulation of blood during percutaneous coronary intervention in heparin-induced thrombocytopenia (HIT) type II (including cases of onset risk) The activated whole blood clotting time (ACT) is measured about 10 minutes from the start of administration of this drug, and the continuous dosage should be adjusted so that ACT will be 250 to 450 seconds until 4 hours after the operation. Depending on the condition of the patient, whether or not continuation of anticoagulant therapy is continued after 4 hours after operation is judged. If it is necessary to continue anticoagulant therapy afterwards, after a reduction to 0.7 μg / kg / min, aPTT The aPTT should be measured once a day after adequately adjusting the continuous dosage so that aPTT is about 1.5 to 3 times the pre-administration value, and reaching the target range. If anticoagulation therapy is needed after 4 hours postoperatively for patients with hepatic impairment in which the clearance of this drug is lowered, be careful not to reduce it to 0.2 μg/kg/min. Until aPTT reaches the target range, measure aPTT as appropriate and measure aPTT once a day after reaching the target range. When starting treatment with this drug and when changing the dose, refer to the table below and administer it. When this drug is diluted to 10 mL and administered at 6μg/kg/ min, the administration rate The administration rate when this drug is diluted to 20 mL and administered at 0.7μg/kg/min or 0.2μg/kg/min It is necessary to continue anticoagulant therapy after 4 hours after surgery, and if this drug is reduced to 0.7 μg / kg / min and then aPTT exceeds 3 times the pre-administration value, administration of this drug is discontinued about. When resuming administration of this drug, confirm that aPTT has recovered to the treatment area (1.5 to 3 times the pre-administration value), and the dose at restart is 1/2 dose before discontinuation To be a guide. When used to suppress the onset of thrombosis in heparin-induced thrombocytopenia (HIT) type II Care should be taken to start administration from low doses (0.2 μg/kg / min) for patients with liver dysfunction or for patients at risk of bleeding, the clearance of which is lowered. When treatment with this drug is started, administration should be started with reference to the table below. When this drug is diluted to 20 mL and administered at 0.7μg/ kg/min or 0.2μg/kg/min, the administration rate After the administration of this drug, a dose should be adjusted so that aPTT is 1.5 to 3 times the pre-administration value and 100 seconds or less. In patients with bleeding risk, a dose should be adjusted so that aPTT is 1.5 to 2 times the pre-administration value. APTT is measured 2 hours after the administration of this drug or 2 hours after the change in the dose of this drug as a guide and the dose is adjusted. For patients with liver dysfunction or patients with bleeding risk, it is desirable to measure aPTT even at the start of treatment with this drug or after 6 hours of dose change. Until aPTT reaches the target range, measure aPTT as appropriate and measure aPTT once a day after reaching the target range. If aPTT exceeds three times the pre-administration value or 100 seconds, administration of this drug should be discontinued. When resuming administration of this drug, confirm that aPTT has recovered to the treatment area (1.5 to 3 times the pre-administration value and 100 seconds or less) and start with 1/2 dose before discontinuation as a guide about. If platelet count is recovered by using this drug and stabilized, start of treatment with oral anticoagulant (warfarin etc.) should be considered. If you switch to warfarin, use this drug for 5 days with warfarin. When using this drug in conjunction with warfarin, monitor aPTT and prothrombin time - international standard ratio (PT - INR). Note that PT - INR is prolonged by interaction between this drug and warfarin, so that PT - INR shortens after discontinuation of this drug. Do not use this drug inadvertently, except for patients who are difficult to switch to oral anticoagulation therapy (the period of administration of this drug in domestic and overseas clinical trials was approximately 7 to 14 days, clinical practice in Japan In the study, the duration of administration in one patient who could not switch to warfarin was up to 35 days). Careful Administration Patients with possible bleeding: Patients with gastrointestinal ulcers, visceral tumors, diverticulitis of the gastrointestinal tract, colitis, subacute bacterial endocarditis, patients with a history of cerebral hemorrhage, patients with reduced platelets, Severe Hypertension, Patients with Severe Diabetes Mellitus, Patients After Surgery [May cause bleeding.] Patients receiving an anticoagulant, a drug having platelet aggregation inhibitory action, a thrombolytic agent or an enzyme preparation having a fibrinogen lowering action [in combination with these drugs, there is a risk of increasing bleeding tendency. (See "Interaction" section)] Patients with severe hepatic disorder [There is a danger that blood levels of this drug will rise.] Serious side effects Hemorrhagic cerebral infarction (1.2% investigation of acute phase of cerebral thrombosis) Hemorrhagic cerebral infarction may occur when used in patients with acute cerebral thrombosis, so observe thoroughly and if abnormalities are found, discontinue administration and take appropriate measures. (See the "Warning" section) Cerebral haemorrhage (0.1%), gastrointestinal bleeding (0.2%) Cerebral haemorrhage and gastrointestinal bleeding may occur, so observe thoroughly and if abnormality is found, discontinue administration and take appropriate measures. Shock · Anaphylactic shock (Frequency unknown) Shock and anaphylactic shock (urticaria, blood pressure lowering, dyspnea, etc.) may occur, so observe thoroughly and if abnormality is found, discontinue administration and take appropriate measures. Fulminant hepatitis (frequency unknown), liver dysfunction (investigation of 0.02% chronic arterial occlusion), jaundice (0.03% acute phase of cerebral thrombosis) Severe hepatic function disorder such as fulminant hepatitis, jaundice may appear. If observation is done sufficiently and abnormality is observed, administration should be stopped immediately and appropriate measures should be taken. Medicinal pharmacology Extended action of human blood clotting time Partial thromboplastin time (PTT) was increased 1.57 times and PT was increased to 1.18 times when intravenous drip infusion of 2.25 mg of this drug to healthy adults over 30 minutes. When persistent intravenous drip infusion of 60 mg of this drug per day to patients with acute cerebral thrombosis for 2 days, aPTT was extended to 1.53 times. When intravenous drip infusion of 10 mg of this drug over 3 hours to a patient with chronic arterial occlusion disease, aPTT was extended to 1.38 times. When 12 - 48 mg of this drug was administered to hemodialysis patients per hour, PTT was extended to 3.4 times. Action on hypercoagulable state in acute phase of cerebral thrombosis Fibrinopeptide A (FPA) was significantly decreased by administration of this drug in patients with acute phase of cerebral thrombosis. Effect on oxygen oxygen partial pressure of avascular limb etc In the patients with chronic arterial occlusion, transdermal tissue oxygen partial pressure, skin temperature, deep temperature of the avascular limb significantly increased by administration of this drug. Selective antithrombin action In vitro tests strongly inhibited the formation of fibrin by thrombin, platelet aggregation and vasoconstriction. The inhibitory effect on other trypsin-like serine proteases was remarkably weak, and the action was thrombin selective. Extension action of blood coagulation time In the in vitro test, aPTT was extended depending on the concentration. A rapid extension like heparin was not observed. Effect in various models Cerebral thrombosis For the middle cerebral artery thrombosis model (rat) by photosensitization reaction, Ischemic Penumbra showed improvement of local cerebral blood flow, suppression of fibrin micro thrombus formation, suppression of infarct region expansion and improvement of hemiplegic-like neurological symptoms. Chronic arterial occlusion For the peripheral arterial obstruction model (rat) by lactic acid injection in the femoral artery, the development of the lesion was suppressed. Extracorporeal circulation Suppressed thrombus formation in antithrombin III lowering animals (rat, mouse). Heparin did not inhibit thrombus formation in the same test. For extracorporeal circulation model (dog), extracorporeal circulation could be performed by using this drug alone. -------------------------------------------------- 注：以下产品不同的厂家和不同价格，采购以咨询为准！ -------------------------------------------------- 产地国家: 日本 原产地英文商品名: NOVASTAN HI INJ(ノバスタンHI注) 10MG/2ML/amps 10amps/BOX 原产地英文药品名: ARGATROBAN HYDRATE 原产地英文化合物名称: (2R,4R)-4-Methyl-1-[N-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)sulfonyl]-L-arginyl]-2-piperidinecarboxylic acid 中文参考商品译名: NOVASTAN HI注射剂(ノバスタンHI注) 10毫克/2毫升/安醅 10安醅/盒 中文参考药品译名: 阿加曲班水合物 中文参考化合物名称: （2R，4R）-4-甲基-1-[N-（（R，S）-3-甲基-1，2，3，4-四氢-8-喹啉磺酰基）-L-精氨酰基]-2-哌啶羧酸 生产厂家中文参考译名: 田辺三菱製薬 生产厂家英文名: Mitsubishi Tanabe Pharma -------------------------------------------------- 产地国家: 日本 原产地英文商品名: NOVASTAN HI INJ(ノバスタンHI注)10MG/20ML/amps 10amps/BOX 原产地英文药品名: ARGATROBAN HYDRATE 原产地英文化合物名称: (2R,4R)-4-Methyl-1-[N-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)sulfonyl]-L-arginyl]-2-piperidinecarboxylic acid 中文参考商品译名: NOVASTAN HI注射剂(ノバスタンHI注) 10毫克/20毫升/安醅 10安醅/盒 中文参考药品译名: 阿加曲班水合物 中文参考化合物名称: （2R，4R）-4-甲基-1-[N-（（R，S）-3-甲基-1，2，3，4-四氢-8-喹啉磺酰基）-L-精氨酰基]-2-哌啶羧酸 生产厂家中文参考译名: 田辺三菱製薬 生产厂家英文名: Mitsubishi Tanabe Pharma -------------------------------------------------- 产地国家: 日本 原产地英文商品名: ARGATROBAN INJECTION SYRINGE(アルガトロバン) 10mg/20ml/amp 10amps/box 原产地英文药品名: ARGATROBAN HYDRATE 原产地英文化合物名称: (2R,4R)-4-Methyl-1-[N-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)sulfonyl]-L-arginyl]-2-piperidinecarboxylic acid 中文参考商品译名: 阿加曲班注射剂(アルガトロバン) 10毫克/20毫升/安醅 10安醅/盒 中文参考药品译名: 阿加曲班水合物 中文参考化合物名称: （2R，4R）-4-甲基-1-[N-（（R，S）-3-甲基-1，2，3，4-四氢-8-喹啉磺酰基）-L-精氨酰基]-2-哌啶羧酸 生产厂家中文参考译名: ニプロファーマ沢井製薬 生产厂家英文名: nipro-pharma