产地国家：美国

处方药：是

所属类别： 20毫升/瓶

包装规格： 20毫升/瓶

计价单位：瓶

生产厂家英文名：SMITHKLINE BEECHAM

原产地英文商品名：BEXXAR 131 IODINE DOSIMETRIC 20mL/Vial

原产地英文药品名：TOSITUMOMAB IODINE-131

中文参考商品译名：百克沙 131 IODINE DOSIMETRIC 20毫升/瓶

中文参考药品译名：托西莫单抗 IODINE-131

简介：

部份中文托西莫单抗处方资料（仅供参考）

药品英文名：Tositumomab

药品别名：Bexxar

药物剂型：托西莫单抗注射剂：225mg；35mg，蛋白浓度为14mg/ml。131I-托西莫单抗注射剂：20ml，含131I 0.61mCi，蛋白浓度0.1mg/ml。

药理作用：托西莫单抗是一种在正常及恶性B淋巴细胞表面发现的鼠抗CD20抗原IgG2aλ单克隆抗体，能与CD20抗原特异结合(人B淋巴细胞耐受分化抗原，Bp35或B1)。该抗原前B淋巴细胞表达的跨膜磷蛋白，在发育成熟的B淋巴细胞中浓度高，该抗原也在90%以上的非霍奇金淋巴瘤(NHL)上表达。抗原决定簇的识别在CD20抗原细胞外，CD20不随抗体结合而从细胞表面脱落，也不嵌入细胞。作用机制可能包括：诱导细胞凋亡，补体依赖细胞毒性(CDC)，抗体依赖性细胞介导的细胞毒作用(ADCC)。另外，细胞凋亡也与同位素的放射有关。本品能够促进机体免疫系统攻击癌细胞并将一定剂量的放射引向肿瘤部位。

药动学：NHL患者静注485mg托西莫单抗后平均血浆清除率为68.2mg/h，本品在肿瘤负荷高、脾脏大或骨转移的患者中具有清除率加快、消除半衰期短、表观分布容积大的特点。131I的消除经衰变，由肾脏排出。5天后67%注射剂量被清除，其中78%从尿中回收。

适应证：用于治疗表达CD20抗原的复发性或难治性低分度滤泡状或已变形的NHL患者，包括那些对利妥昔单抗无应答的难治性NHL患者。

禁忌证：本品禁用于孕妇或对该疗法中任一成分过敏的患者。

注意事项：1.本品对生存率的作用尚未可知。2.本品不能用作CD20抗原阳性NHL患者的初始疗法。3.本品只能使用一个疗程。多个疗程或者与其他放疗或化疗联用的安全性还未评估。4.托西莫单抗注射剂2～8℃保存。溶解后2～8℃可保存24h，室温可保存8h。131I-托西莫单抗注射剂2～8℃保存。溶解后2～8℃或室温可保存8h。不良反应本品可致大多数患者血细胞(血小板、白细胞以及红细胞)计数严重下降。约一半的患者发生感染，1/8的患者出血，近1/4的患者需要支持性医护。其他与输液有关的较轻的不良反应包括发热、寒战、出汗、恶心、低血压、呼吸短促和呼吸困难。在给予本品后，可能会增加患甲状腺功能低下的风险。

用法用量：本品治疗分两个独立阶段：剂量测定阶段为7～14天，随后为治疗阶段。

1.剂量测定阶段：(1)托西莫单抗450mg溶于0.9%氯化钠注射液50ml中静滴60min以上。若出现轻、中度毒性，滴速降低50%，若出现严重毒性应停药。(2)131I-托西莫单抗(含蛋白35mg，131I 5.0mCi)溶于0.9%氯化钠注射液30ml中静滴20min以上。若出现轻、中度毒性，滴速降低50%，若出现严重毒性应停药。

2.治疗阶段：(1)托西莫单抗450mg溶于0.9%氯化钠注射液50ml中静滴60min以上。若出现轻、中度毒性，滴速降低50%，若出现严重毒性应停药。(2)131I-托西莫单抗：根据说明书所标活性浓度计算治疗所需131I-托西莫单抗剂量。若出现轻、中度毒性，滴速降低50%，若出现严重毒性应停药。(3)血小板≥150000/mm3者剂量：131I 75cGy全身照射，托西莫单抗35mg静滴20min。(4)血小板100000～150000/mm3者剂量：131I 65cGy全身照射，托西莫单抗35mg静滴20min。

3.联合治疗：患者给予以下辅助治疗后方可用托西莫单抗治疗。饱和碘化钾溶液，口服，每次4滴，每日3次；卢戈碘溶液：口服，每次20滴，每日3次，或碘化钾片每日130mg。甲状腺保护剂应在131I-托西莫单抗治疗前24h开始使用，持续到131I-托西莫单抗治疗后2周。托西莫单抗治疗前30min给予对乙酰氨基酚650mg口服，苯海拉明50mg口服。

英文版说明书

INDICATIONS AND USAGERelapsed or Refractory CD20-Positive, Non-Hodgkin’s LymphomaThe BEXXAR therapeutic regimen (tositumomab and iodine I 131 tositumomab) is indicated for the treatment of patients with CD20-positive relapsed or refractory, low grade, follicular, or transformed non-Hodgkin’s lymphoma who have progressed during or after rituximab therapy, including patients with rituximab-refractory non-Hodgkin’s lymphoma.Determination of the effectiveness of the BEXXAR therapeutic regimen is based on overall response rates in patients whose disease is refractory to chemotherapy and rituximab. The effects of the BEXXAR therapeutic regimen on survival are not known.Important Limitations of Use• The BEXXAR therapeutic regimen is only indicated for a single course of treatment.• The safety and efficacy of additional courses of the BEXXAR therapeutic regimen have not been established.• The BEXXAR therapeutic regimen is not indicated for first-line treatment of patients with CD20-positive non-Hodgkin’s lymphoma.BOXED WARNINGS AND ADDITIONAL IMPORTANT SAFETY INFORMATIONWARNING: SERIOUS ALLERGIC REACTIONS (INCLUDING ANAPHYLAXIS), PROLONGED AND SEVERE CYTOPENIAS, AND RADIATION EXPOSURESerious Allergic Reactions (Including Anaphylaxis): Serious, including fatal, allergic reactions have occurred during or following administration of the BEXXAR therapeutic regimen. Have medications for the treatment of allergic reactions available for immediate use. Permanently discontinue the BEXXAR therapeutic regimen for serious allergic reactions and administer appropriate medical treatment [see Warnings and Precautions (5.1)].Prolonged and Severe Cytopenias: The BEXXAR therapeutic regimen resulted in severe and prolonged thrombocytopenia and neutropenia in more than 70% of the patients in clinical studies. The BEXXAR therapeutic regimen should not be administered to patients with greater than 25% lymphoma marrow involvement, platelet count less than 100,000 cells/mm3 or neutrophil count less than 1,500 cells/mm3 [see Warnings and Precautions (5.2), Adverse Reactions (6.1)].Radiation Exposure: The BEXXAR therapeutic regimen may be administered only under the supervision of physicians who are certified under or participating in the BEXXAR therapeutic regimen certification program and who are authorized under the Radioactive Materials License at their clinical site. Follow institutional radiation safety practices and applicable federal guidelines to minimize radiation exposure during handling and after administration of the BEXXAR therapeutic regimen [see Warnings and Precautions (5.3)].ADDITIONAL IMPORTANT SAFETY INFORMATIONSerious Allergic Reactions, Including Anaphylaxis: The BEXXAR therapeutic regimen can cause severe, including fatal, allergic reactions. In clinical trials, 14 patients (6%) experienced allergic reactions. Premedicate with acetaminophen and diphenhydramine. Have medications for the treatment of allergic reactions available for immediate use during administration. Signs and symptoms of severe allergic reactions may include fever, rigors or chills, sweating, hypotension, dyspnea, bronchospasm, and nausea during or within 48 hours of infusion. Immediately interrupt BEXXAR infusions for severe reactions and provide appropriate medical and supportive care measures. Permanently, discontinue the BEXXAR therapeutic regimen in patients who develop serious allergic reactions.Prolonged and Severe Cytopenias: Patients receiving the BEXXAR therapeutic regimen experienced severe (NCI CTC grade 3-4) and prolonged neutropenia (63%), thrombocytopenia (53%), and anemia (29%). The time to nadir was 4 to 7 weeks and the duration of cytopenias was approximately 30 days. Due to the variable nature of the onset of cytopenias, monitor patients with weekly complete blood counts for up to 12 weeks. The BEXXAR therapeutic regimen should not be administered to patients with >25% lymphoma marrow involvement, platelet count <100,000 cells/mm3, or neutrophil count <1,500 cells/mm3.Radiation Exposure: The BEXXAR therapeutic regimen contains Iodine-131. Follow institutional radiation safety practices and applicable federal guidelines to minimize radiation exposure during handling and after administration of the BEXXAR therapeutic regimen. Advise patients of the risks of radiation exposure of household contacts, pregnant women, and small children and of the steps to be taken to reduce these risks. The BEXXAR therapeutic regimen should be administered only by physicians enrolled in the certification program for dose calculation and administration of the BEXXAR therapeutic regimen. Further information regarding the BEXXAR therapeutic regimen certification program is available by phone at 1-877-423-9927.Secondary Malignancies: Myelodysplastic syndrome (MDS) or acute leukemia may occur with the use of the BEXXAR therapeutic regimen and were reported in 10% of patients enrolled in clinical trials and in 3% of patients enrolled in the expanded access program (median follow-up 39 and 27 months, respectively). The median time to development of MDS or leukemia was 31 months. Non-hematologic malignancies may occur with the use of the BEXXAR therapeutic regimen and were reported in 5% of patients enrolled in clinical trials or the expanded access program. In the absence of controlled studies, the relative risk of secondary malignancies in patients receiving the BEXXAR therapeutic regimen cannot be determinedHypothyroidism: The BEXXAR therapeutic regimen can cause hypothyroidism. Initiate thyroid-blocking medications at least 24 hours before administering the dosimetric dose and continue until 14 days after the therapeutic dose. The risk of hypothyroidism is likely to be increased in patients who do not complete the recommended thyroid-protective regimen. eva luate for clinical evidence of hypothyroidism and thyroid-stimulating hormone (TSH) level before treatment and annually thereafter. In clinical studies, 203 patients did not have elevated TSH at study entry. Of these, 137 patients had at least one post-treatment TSH value available and were not taking thyroid hormonal treatment at study entry. With a median follow up of 46 months, the incidence of hypothyroidism (elevated TSH or initiation of thyroid replacement therapy) was 18% with a median time to development of 16 months. The cumulative incidences of hypothyroidism at 2 and 5 years in these 137 patients were 11% and 19%, respectively. Onset of hypothyroidism has occurred up to 90 months post-treatment.Embryo-fetal Toxicity: The BEXXAR therapeutic regimen can cause fetal harm when administered to a pregnant woman including severe, and possibly irreversible, neonatal hypothyroidism. Inform patients who are pregnant or become pregnant after the BEXXAR therapeutic regimen about the potential hazard to a fetus. eva luate infants born to mothers treated with the BEXXAR therapeutic regimen during pregnancy for hypothyroidism at time of delivery and during the neonatal period. Patients should use effective contraception during treatment with the BEXXAR therapeutic regimen and for 12 months after the therapeutic dose.Nursing Mothers: Because immunoglobulins are secreted in human milk, it is expected that tositumomab would be present in human milk. Radiolabeled iodine is excreted in breast milk and may reach concentrations equal to or greater than maternal plasma concentrations. Because of the potential for serious adverse reactions in nursing infants from the BEXXAR therapeutic regimen, advise women to discontinue nursing or to consider alternative treatment, taking into account the importance of the BEXXAR therapeutic regimen to the mother.Excessive Radiation Exposure in Patients With Impaired Renal Function: There are no data regarding the safety of administration of the BEXXAR therapeutic regimen in patients with impaired renal function. Since the BEXXAR therapeutic regimen is primarily cleared through the kidneys, the rate of excretion of radiolabeled iodine is expected to be decreased in patients with impaired renal function or obstructive uropathy, which may result in increased patient exposure to I-131 tositumomab.Immunization: The safety of immunization with live viral vaccines following administration of the BEXXAR therapeutic regimen and the ability to generate a primary or anamnestic humoral response to any vaccine have not been studied. Do not administer live viral vaccines to patients recently treated with BEXXAR.Immunogenicity Human Anti-mouse Antibody (HAMA): There is a potential for immunogenicity with therapeutic proteins such as tositumomab. In clinical trials (N = 219), 11% of patients who received BEXXAR developed HAMA seropositivity. Ten percent (10%) of the patients in the expanded access program (N = 569) developed HAMA seropositivity. The post-treatment incidences of HAMA seropositivity at 6, 12, and 18 months were 6%, 17%, and 21%, respectively.Assessment of Biodistribution: The biodistribution of Iodine I 131 Tositumomab should be assessed. If biodistribution is altered, the therapeutic dose should not be administered.Adverse Reactions: The most common adverse reactions (>25%) during therapy with BEXXAR were neutropenia (63%), thrombocytopenia (53%), anemia (29%), infections (including pneumonia, bacteremia, septicemia, bronchitis, and skin infections) (45%), infusion reactions (29%), asthenia (46%), fever (37%), and nausea (36%). The most common Grade 3 and 4 adverse (NCI CTC grade 3-4) with BEXXAR were neutropenia (7%), thrombocytopenia (7%), anemia (5%), infections (including pneumonia, bacteremia, septicemia, bronchitis, and skin infections) (9%), serious allergic reactions (including bronchospasms and angioedema) (14 patients [6%]), infusion reactions (67 patients [29%]), and secondary leukemia/myelodysplastic syndrome (24/230 patients [10%]).