部分中文Nulojix处方资料（仅供参考） Nulojix（belatacept）用于肾移植成人患者以预防急性排斥反应 美国食品和药品监督管理局(FDA)准Nulojix(belatacept)在成年患者肾移植中预防急性排斥。本药被批准与其它免疫抑制剂(抑制免疫系统药物)使用--特别是巴利昔单抗[basiliximab]，麦考酚酸酯[mycophenolate mofetil]，和皮质激素。 Nulojix是一类药物被称为选择性T细胞共刺激阻断剂。药物有助于预防肾移植后器官排斥。无免疫抑制, 机体可能排斥被移植器官因为免疫系统是被新器官为外来物(移植物排斥)。通过预防排斥，Nulojix，经历30分钟静脉输注，与其它免疫抑制剂一起工作以保持新肾工作。 药品名称：Nulojix（Belatacept） 化学结构：可溶性 C T L A 4重组免疫球蛋白融合蛋白 批准日期：2011年6月15日 适应症：Belatacept与人白介素2（IL-2）拮抗剂、霉酚酸（MPA）和皮质甾类药物联用，预防肾移植受者出现排异反应，同时维持植肾功能。 作用机制： T细胞的完全活化需要T细胞受体与抗原递呈 细胞(APCs) 的相互作用以及另一种受体分子相互作用引起的共刺激信号，而在免疫反应中，这种共刺激信号尤为重要， 其可通过调节 T细胞活性， 控制自身免疫疾病、下调炎症反应和抑制同种异体移植 排斥反应。CD28：B7途径便是最典型的共刺激途径，CD28是免疫球蛋白超家族的跨膜成员，表达于几乎所有的幼稚 T细胞，是最重要的T细胞活化共刺激受体之一，而其同源的CTLA4则被认为是一个T细胞活化的免疫调节因子和一个负共刺激分子；这两种分子拥有共同的配体， 即表达于APCs的B7家族受体 B7.1(CD80)和B7-2(CD86) 。阻断这些 分子间的相互作用，即可导致免疫无应答或沉默， 即 所谓“无反应性”。如今，应用重组技术手段，已能成功开发可竞争性抑制两种 B7分子与其受体相互作用的融合蛋白。由美国百时美施贵宝(B MS) 公司开发的belatacept(BMS-224818) 就是一种第 2代 可溶性 CTLA4重组免疫球蛋白融合蛋 白，由人CTLA4胞外区和经修饰的人IgG1Fc区片段构成，静注给药后可特异性靶向 T细胞完全活化所需的关键共刺激信号，较其母体化合物 abatacept，更增强了与B7受体的结合力，为首例合理设计的能更有效阻断主要 T细胞共刺激途径的可注射用免疫抑制融合蛋白，它可使接受肾移植的患者避免使用如环孢素等钙调神经素抑制剂，后者的长期使用可能会在一定程度上导致肾、 心血管和代谢毒性。 临床实验： 两项多中心、随机的Ⅲ期临床研究共注册有1200名成年肾移植患者，在用药6个月后活检检移植肾的急性排斥反应发生率为治疗指标。阳性对照物为环孢素（cyclosporine）。临床实验包括b e l atacept 的强化 和非强化 治疗，或环孢素 的基本免疫抑制治疗。belatacept的强化和非强化治疗均包括一个早期阶 段( 本品用量为10毫克/公斤) 和一个后期阶段(本品用量为5毫克/公斤)，两个阶段治疗间隔4或8周，belatacept强化治疗组的早期阶段较其非强化治疗组更长( 6个月3个月) ，且给药次数也更多；同时， 所有受试者均接受 basilixi ma b的诱导治疗与霉酚酸酯和皮质类固醇的辅助维持治疗。6个月时，belatacept强化和非强化治疗组及环孢素治疗组的急性排斥反应发生率相近， 分别为7％、6％和8％，达到了预先设定的 belatacept与环孢素相比的非劣效性标准；12个月时，belatacept治疗组受试者的肾小球滤过率明显高于环孢素治疗组，且慢性移植肾肾病发生率低于环孢素治疗组，血脂和血压也较环孢素治疗组更低或相近。表明 belatace pt具有与环孢素相似的免疫抑制功效， 且在降低心血管和代谢风险以及慢性移植肾肾病发生率、 保护肾功能等方面更显优势。 Nulojix Marketed by: Bristol-Myers Squibb (Princeton, NJ) Indication: Nulojix (belatacept) is the first selective T-cell costimulation blocker indicated for the prophylaxis of organ rejection in adults receiving a kidney transplant to be approved by the FDA. Nulojix is administered in combination with basiliximab induction, myophenolate mofetil, and corticosteroids, and should be used only in patients who are positive for Epstein-Barr virus. It is administered by intravenous infusion over 30 minutes, and is not approved for the prophylaxis of other transplanted organs. Nulojix carries a boxed warning against post-transplant lymphoproliferative disorder, other malignancies, and serious infections. Dosage Form: Lyophilized powder for intravenous injection: 250 mg per vial --------------------------------------------------------- NULOJIX; (belatacept) is approved for the prophylaxis of organ rejection in adult patients receiving a kidney transplant, in combination with basiliximab induction, mycophenolate mofetil (MMF), and corticosteroids. Use NULOJIX only in patients who are Epstein-Barr virus (EBV) seropositive. Use of NULOJIX for prophylaxis of organ rejection in transplanted organs other than kidney has not been established. Selected Important Safety Information: NULOJIX is associated with increased risk for post-transplant lymphoproliferative disorder (PTLD), predominantly in the central nervous system (CNS). NULOJIX is contraindicated in patients who are EBV seronegative or with unknown serostatus because the risk of PTLD is particularly increased in patients who are EBV seronegative. NULOJIX is to be used only in patients who are EBV seropositive. Patients should be monitoredforneworworseningneurological, cognitive, or behavioral signs and symptoms. Higher than recommended doses or more frequent dosing of NULOJIX and concomitantimmunosuppressivesisnotrecommended. Immunosuppression may result in increased susceptibility to infection and development of malignancies. NULOJIX should be prescribed only by physiciansexperienced inimmunosuppressive therapy and management of kidney transplant patients. Use in liver transplant patients is not recommended due to an increased risk of graft loss and death. Continue to read Important Safety Information >> Dosage Formulation and Strength: 250 mg lyophilized powder for injection, for intravenous use.                    IMPORTANT SAFETY INFORMATION Post-Transplant Lymphoproliferative Disorder (PTLD)NULOJIX patients are at increased risk for developing PTLD, predominantly involving the central nervous system (CNS)Recipients without immunity to EBV (ie, seronegative) are at particularly increased risk; therefore, NULOJIX is contraindicated in transplant recipients who are EBV seronegative or unknown serostatus Monitor for new or worsening neurological, cognitive, or behavioral signs and symptomsAs the total burden of immunosuppression is a risk factor for PTLD, higher than recommended doses or more frequent dosing of NULOJIX or concomitantimmunosuppressive agents are not recommendedOther known risk factors for PTLD include cytomegalovirus (CMV) infection and T-cell-depleting therapy CMV prophylaxis is recommended for at least 3 months after transplantationUse T-cell-depleting therapy to treat acute rejection cautiouslyPatients who are EBV seropositive and CMV seronegative may be at increased risk of PTLDSince CMV seronegative patients are at increased risk for CMV disease (a known risk factor for PTLD), the clinical significance of CMV serology for PTLD remains to be determined; however, these findings should be considered when prescribing NULOJIX Management of Immunosuppression Only physicians experienced in immunosuppressive therapy and management of kidney transplant patients should prescribe NULOJIX Patients should be managed in facilities with adequate laboratory and supportive medical resources  The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient Progressive Multifocal Leukoencephalopathy (PML)NULOJIX® (belatacept) patients are at increased riskforPML,oftenarapidlyprogressiveandfatalopportunistic infectionIn clinical trials, two cases were reported in patients receiving NULOJIX at higher cumulative doses and more frequently than the recommended regimen, along with MMF and corticosteroids; one occurred in akidneytransplant recipient and one occurred in a liver transplantrecipientAsPMLhasbeenassociatedwithhighlevelsofimmunosuppression, higher than recommended doses or more frequent dosing of NULOJIX andconcomitantimmunosuppressive agents, including MMF, are not recommendedMonitor for new or worsening neurological, cognitive, or behavioral signs and symptoms PML is usually diagnosed by brain imaging, cerebrospinal fluid testing for JC viral DNA by polymerasechainreaction, and/or brain biopsy Consultation with a specialist should be considered If PML is diagnosed, consider reduction or withdrawal of immunosuppression, weighing risk to the graftOther Malignancies and Serious InfectionsIncreased susceptibility to infection and possible development of malignancies may result from immunosuppressionPatients should avoid prolonged exposure to ultraviolet light and sunlightPatients receiving immunosuppressants, including NULOJIX, are at increased risk for bacterial, viral, fungal, and protozoal infections, including opportunistic infections and tuberculosis.  Some infections were fatal Polyoma virus-associated nephropathy can lead to deteriorating renal function and graft loss;considerreductioninimmunosuppression, weighing risk to the graft Tuberculosis was more frequently observed in patients receiving NULOJIX. Evaluate for tuberculosis and initiate treatment for latent infection prior to NULOJIX useCMV and Pneumocystis jiroveci prophylaxis is recommended after transplantationLiver Transplant: use in liver transplant patients is not recommended due to increased risk of graft loss and death in a clinical trial with more frequent administration of NULOJIX than studied in kidney transplant, along with MMFandcorticosteroidsImmunizations: avoid use of live vaccines during NULOJIX treatment Pregnancy Category C: based on animal data, NULOJIX may cause fetal harm. NULOJIX should not be used in pregnancy unless potential benefit to the mother outweighs potential risk to the fetus. To monitor maternal-fetal outcomes of pregnant women who have received NULOJIX, or whose partners have received NULOJIX, healthcare providers are strongly encouraged to register pregnant patients in the National Transplant Pregnancy Registry (NTPR) by calling 1-877-955-6877 Nursing Mothers: discontinue NULOJIX® (belatacept) or nursing, considering importance of NULOJIX to the mother Most Common Adverse Reactions (≥20%): anemia (45%), diarrhea (39%), urinary tract infection (37%), peripheral edema (34%), constipation (33%), hypertension (32%), pyrexia (28%), graft dysfunction (25%), cough (24%), nausea (24%), vomiting (22%), headache (21%), hypokalemia (21%), hyperkalemia (20%), and leukopenia (20%) FDA批准Nulojix用于肾移植患者 美国FDA2011年6月15日批准belatacept（Nulojix），以防止接受肾移植手术的成年患者产生急性排斥反应。该药物被批准用于与其他免疫抑制剂（抑制免疫系统药物）同时使用——特别是巴利昔单抗（basiliximab）、吗替麦考酚酯（mycophenolate mofetil）和糖皮质激素corticosteroids。 本品是一种称为选择性T细胞共刺激阻断剂的药物。这种药物有助于预防肾移植手术后的器官排斥。如果没有免疫抑制，身体会对被移植器官产生排异，这是由于免疫系统将新器官识别为外来者（移植排斥反应）。静脉输液本品30分钟，可通过防止排斥反应，与其他免疫抑制剂一起作用以保持新的肾脏。 “Nulojix为肾移植患者带来了新的选择，”FDA药物评价和研究中心抗菌产品办公室主任，医学博士、公共卫生硕士Edward Cox说。 “这种新的药物与其他免疫抑制剂联合使用有助于控制免疫系统，防止接受肾脏移植的患者对器官的排斥反应。” 两项开放性随机多中心III期试验研究对Nulojix进行了评估。该研究纳入了超过1200例患者，并将2种不同给药剂量的Nulojix联用其他免疫抑制剂——环孢菌素进行比较。这些研究表明，建议的本品疗法对防止急性器官排斥是安全和有效的。 本品附带一个黑框警示：本品可能增加移植后淋巴增生性障碍（PTLD）的风险，这是一种器官移植后白细胞失控增长的癌症。从未接触过EB病毒（EBV）——单核细胞增多症的病因——的接受过移植手术的患者患上PTLD的风险是很高。未接触过EBV的移植患者如果在移植后产生发生感染，那么他们产生对病毒的有效免疫应答是困难的；通常他们在移植时便暴露在病毒中，因为大约80%的捐赠器官上携带这种病毒。患者应当对EBV进行测试，如果结果显示他们已接触到EBV，那么只能使用Nulojix。另外的黑框警示，同样也是其他免疫抑制剂的黑框警示警告了可能增加产生严重感染和其他癌症的风险。 试验中，移植患者的常见不良反应包括：贫血、便秘、肾脏及膀胱感染、腿脚肿胀等症状。此外，服用者必须尽量减少日晒时间，以预防皮肤癌的发生。Nulojix是经静脉输注用药，输注时间为30分钟。 --------------------------------------------------------------- 原产地英文商品名: NULOJIX 250MG/VIAL 原产地英文药品名: BELATACEPT 中文参考商品译名: NULOJIX 250毫克/瓶 中文参考药品译名: BELATACEPT 生产厂家中文参考译名: 百时美施贵宝 生产厂家英文名: BRISTOL MYERS SQUIBB