Astagraf XL（他克莫司缓释胶囊，tacrolimus extended release capsules）是首个每日一次的他克莫司制剂，该药作为免疫抑制组合方案中的核心组成部分，为肾移植受者预防器官排斥反应提供了一个很有潜力的疗法。 ASTAGRAF XL®（他克莫司缓释胶囊），供口服使用 美国首次批准：2013  生产公司：美国安斯泰来 警告： 恶性肿瘤;严重感染;和死亡率的肝移植的妇女RECIPIENTSSee完整处方为完整的黑框警告信息 •只有医师经验丰富的免疫抑制治疗和器官移植患者的管理应该开ASTAGRAF XL。 •易感染性增加和恶性肿瘤的可能发展可能导致的免疫抑制。 •使用在肝移植中不因死亡率在女性肝移植增加推荐。 作用机制 ActionTacrolimus的机制抑制T淋巴细胞的活化，虽然目前还不知道确切的作用机制。实验证据表明，他克莫司结合到细胞内蛋白，FKBP-12。然后，形成他克莫司的FKBP-12，钙，钙调蛋白，钙调磷酸酶和一种复杂和钙的磷酸酶活性的抑制。这种效果可能会阻止活化的T细胞（NF-AT），以为发起基因转录为淋巴因子（如白细胞介素2，γ干扰素）的形成核组分的核因子的去磷酸化和易位。最终结果是T淋巴细胞的活化（即，免疫抑制）的抑制。 适应症和用法 ASTAGRAF XL是用于器官排斥的预防中接收肾脏移植与霉酚酸酯（MMF）和皮质类固醇，具有或不具有巴利昔单抗诱导的患者指示的钙调神经磷酸酶抑制剂的免疫抑制剂。 使用限制： •不能互换与他克莫司立即释放胶囊 •不要同时使用环孢素 用法用量 推荐的初始口服剂量和肾移植观察全血他克莫司谷浓度的患者。 * 10日-90百分位数。给予首剂前或移栽完毕后48小时内;可能会延迟开始治疗，直至肾功能已经恢复。给再灌注之前，和第一个手术后剂量再灌注后12小时内而不是手术前剂量后小于4小时12小时内的术前剂量。 治疗方案 口服剂量 观察全血谷浓度* 随着巴利昔单抗诱导† 0.15毫克/千克/天 第1天至60：5-17毫微克/毫升 第3个月到12：4-12毫微克/毫升 如果没有感应 手术前：0.1毫克/千克/天 手术后：0.2毫克/千克/天 第1天至60：6-20毫微克/毫升 第3个月到12：6-14毫微克/毫升 •每天一次在早晨乘坐，最好是在空腹;不要随身携带的酒精饮料或柚子汁;不嚼，分割或挤压胶囊。 •全血他克莫司谷浓度监测建议。 剂型和规格 •胶囊：0.5毫克，1毫克，5毫克 禁忌 •ASTAGRAF XL是禁忌的患者过敏的他克莫司。 警告和注意事项 •用药错误的报道，包括立即释放他克莫司和ASTAGRAF XL（缓释）他克莫司制剂之间无意取代。 •新发糖尿病移植后：监测血糖。 •肾毒性（急性和/或慢性）：监测肾功能;减少剂量;小心与其他肾毒性药物。 •神经毒性，后可逆脑病综合征的风险（PRES）：监测的神经系统异常;减少或停止免疫抑制。 •高钾血症：监测血清钾水平;谨慎使用其他药物会增加钾。 •高血压：可能需要降压治疗;监测相关的药物相互作用。 •使用西罗莫司：不推荐;在肝脏和心脏移植的严重不良反应的风险增加。 •请使用强CYP3A抑制剂和诱导剂：他克莫司调整剂量和监测谷浓度以及发生不良反应，包括QT间期延长。 •免疫接种：避免使用活疫苗。 •纯红细胞再生障碍：考虑中止。 不良反应 •最常见的不良反应（≥30％）为：腹泻，便秘，恶心，外周性水肿，震颤和贫血。 要报告疑似不良反应，请与安斯泰来制药美国公司在1-800-727-7003或FDA电话1-800-FDA-1088或www.fda.gov/medwatch。 药物相互作用 •麦考酚酸产品：显示器的MPA相关的不良反应，并根据需要调整MMF或MPA剂量。 •CYP3A抑制剂：他克莫司增加浓度;监测浓度和调整剂量的他克莫司根据需要与同时使用。 •CYP3A诱导剂：降低他克莫司的浓度;监测浓度和调整剂量的他克莫司根据需要与同时使用。 特殊人群中使用 •妊娠：根据动物实验数据可能对胎儿造成伤害。 •哺乳母亲：请停止药物或哺乳。 •肾损害：如果肾毒性的发展，减少剂量。 •肝损伤：下面推荐的起始剂量较低剂量可能需要。 •种族：非洲裔美国人可能需要更高剂量。 生产厂家：安斯泰来（美国公司） ------------------------------------------------ 注：以下产品不同规格和不同价格，购买以咨为准！ ------------------------------------------------ ASTAGRAF XL缓释 5毫克/胶囊    30粒 | 50粒 胶囊/瓶 ASTAGRAF XL缓释 0.5毫克/胶囊 30粒 | 50粒 胶囊/瓶 ASTAGRAF XL缓释 1毫克/胶囊    30粒 | 50粒 胶囊/瓶 ASTAGRAF XLTM (tacrolimus extended-release capsules) for the prophylaxis of organ rejection in patients receiving a kidney transplant used with mycophenolate mofetil (MMF) and corticosteroids, with or without basiliximab induction, "The availability of ASTAGRAF XL marks a significant moment for the transplantation community, giving new adult kidney transplant recipients an additional option in their immunosuppressant care," said James Robinson, President, Astellas Pharma US, Inc. "Astellas has long been a leader in the field of transplant immunology, and we are proud to continue to advance care for transplant recipients." ASTAGRAF XL is the first once-daily oral tacrolimus formulation available in the U.S. for the prophylaxis of organ rejection in adult kidney transplant patients. ASTAGRAF XL was approved by the U.S. Food and Drug Administration (FDA) on July 19, 2013. In total, tacrolimus extended-release capsules have been approved for use in 73 countries. The recommended starting dose of ASTAGRAF XL with basiliximab induction is 0.15 mg/kg once-daily. The recommended starting dose of ASTAGRAF XL without basiliximab induction is 0.1 mg/kg once-daily (pre-operative) and 0.2 mg/kg once-daily (post-operative). It is available in 0.5 mg, 1 mg and 5 mg capsules. About ASTAGRAF XL (tacrolimus extended-release capsules) ASTAGRAF XL capsules is a prescription medicine used with other medicines to help prevent organ rejection in people who have had a kidney transplant. ASTAGRAF XL is an extended-release capsule and is not the same as tacrolimus immediate-release capsules. Your doctor should decide what medicine is right for you. ASTAGRAF XL is not for use with medicines called cyclosporine (Neoral®, Sandimmune®, Gengraf®). It is not known if ASTAGRAF XL is safe and effective when used with sirolimus (Rapamune®) in people who have had kidney transplants. It is not known if ASTAGRAF XL is safe and effective in children under 16 years of age who have had kidney transplants. ASTAGRAF XL Generic Name and Formulations: Tacrolimus 0.5mg, 1mg, 5mg; ext-rel caps. Company: Astellas Pharma US, Inc. Indications for ASTAGRAF XL: Organ rejection prophylaxis in kidney transplant patients, in combination with mycophenolate mofetil (MMF) and corticosteroids, with or without basiliximab induction. Limitations of use: not interchangeable or substitutable with tacrolimus immediate-release caps. Do not use simultaneously with cyclosporine. Adult Dose for ASTAGRAF XL: Swallow whole. Take once daily in the morning, preferably on an empty stomach. If previously on Prograf IV infusion, initial oral dose may be given 8–12 hours after discontinuing infusion. ≥16yrs: with basiliximab induction: initially 0.15mg/kg/day; give first dose prior to or within 48 hours after transplantation; but may be delayed until renal function has recovered; without induction (pre-op): 0.1mg/kg/day; give dose within 12 hours prior to reperfusion when used with MMF and corticosteroids; without induction (post-op): 0.2mg/kg/day; give first dose within 12 hours after reperfusion but not less than 4 hours after pre-op dose when used with MMF and corticosteroids. Black patients may require higher doses. Renal or hepatic impairment: use lowest effective dose. Post-op oliguria: give initial dose no sooner than 6 hours and within 48 hours of transplantation, but may delay therapy until renal function recovers. See full labeling. Children's Dose for ASTAGRAF XL: <16yrs: not established. Pharmacological Class: Immunosuppressant (calcineurin-inhibitor). Warnings/Precautions: Not recommended for use in liver transplantation. Increased risk of infections (eg, bacterial, viral, fungal, protozoal, cytomegalovirus), opportunistic infections including polyoma virus. Increased risk of lymphomas and other malignancies (eg, skin). Avoid sun, UV light. Epstein Barr Virus seronegative. New-onset diabetes: monitor for hyperglycemia. Hepatic or renal impairment; monitor and consider dose reduction. Obtain tacrolimus whole blood concentrations, serum creatinine, potassium, and fasting glucose periodically. Pregnancy (Cat. C), nursing mothers: not recommended. Interactions: Concomitant sirolimus, live vaccines, cyclosporine: not recommended. Concomitant mycophenolic acid (MPA) products; monitor. Concomitant strong CYP3A4 inhibitors/inducers or substrates: must adjust dosing regimen, closely monitor tacrolimus blood concentrations and for QT prolongation. Caution with potassium-sparing diuretics, ACEIs, ARBs. Avoid grapefruit juice, nelfinavir, alcohol. Additive nephrotoxicity with aminoglycosides, ganciclovir, amphotericin B, cisplatin, tenofovir, ritonavir, indinavir. May be potentiated by calcium channel blockers (eg, verapamil, diltiazem, nifedipine), antifungals (eg, fluconazole, ketoconazole), macrolides (eg, troleandomycin, clarithromycin, erythromycin), metoclopramide, lansoprazole, omeprazole, bromocriptine, chloramphenicol, cimetidine, danazol, ethinyl estradiol, amiodarone, methylprednisolone, protease inhibitors (eg, telaprevir, boceprevir, ritonavir), nefazodone, magnesium-aluminum-hydroxide. May be antagonized by carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, caspofungin, St. Johns Wort. Adverse Reactions: Diarrhea, constipation, nausea, peripheral edema, tremor, anemia, headache, abdominal pain, insomnia, hypertension, renal dysfunction, infections (viral, cytomegalovirus, polyoma virus), hypophosphatemia, hyperkalemia, hypomagnesemia, hyperglycemia, nephrotoxicity or neurotoxicity (esp. in high doses), JC virus-associated progressive multifocal leukoencephalopathy, post-transplant diabetes mellitus, posterior reversible encephalopathy syndrome (consider reduced dose or discontinue), malignancies (lymphomas, skin), post-transplant lymphoproliferative disorder, pure red cell aplasia (consider discontinuation). How Supplied: Ext-rel caps—30, 50 http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=550a5cd4-fbf2-4c09-b577-6bde8fcbdf6e