通用名：注射用硼替佐米、

商品名称：万珂TM(Velcade®)

英文名：Bortezomib for Injection

汉浯拼音：Zhusheyong  Pengtizuomi

分子式：C19H25BN4O4

分子量：384。24
　　
本品主要成份为硼替佐米，其化学名称为：[(1R)-3-甲基-1-[[(2S)-1-氧-3-苯基-2-[(吡嗪羧基)氨基]丙基]氨基]丁基]硼酸

性状
本品为白色或类白色块状物或粉末。

药理毒理

药效学

硼替佐米是哺乳动物细胞中26S蛋白酶体糜蛋白酶样活性的可逆抑制剂。26S蛋白酶体是一种大的蛋白质复合体，可降解泛蛋白。泛蛋白酶体通道在调节特异蛋白在细胞内浓度中起到重要作用，以维持细胞内环境的稳定。蛋白水解会影响细胞内多级信号串联，这种对正常的细胞内环境的破坏会导致细胞的死亡。而对26S蛋白酶体的抑制可防止特异蛋白的水解。体外试验证明硼替佐米对多种类型的癌细胞具有细胞毒性。临床前肿瘤模型体内试验证明硼替佐米能够延迟包括多发性骨髓瘤在内的肿瘤生长。

毒理学

尚未进行硼替佐米的致癌性研究。

用中国仓猝鼠卵巢细胞进行体外染色体畸变分析显示硼替佐米有诱裂活性(染色体结构畸变)。体外诱变性分析(埃姆斯试验)和小鼠体内小核分析结果显示硼替佐米没有基因毒性。

尚未对生育影响进行研究，但是在一般毒理学研究中对生殖组织进行了评价。6个月的大鼠毒理研究显示，剂量≥0.3mg／㎡(临床推荐剂量的1/4)时发现对卵巢有变性的作用，剂量为1.2mg／㎡时发现有变性的改变。本品可能对男性或女性的生育能力有潜在影响。

药代动力学

对8名多发性骨髓瘤患者静脉给予本品1.3mg／㎡，最大血药浓度中值为509ng／m1(范围109—1300ng／m1)，肌酐清除率为3l—169ml／min。对晚期恶性肿瘤患者给予本品1.45—2.00mg／㎡，首剂量后的平均消除半衰期为9—15小时。作为单药，推荐剂量的硼替佐米在多发性骨髓瘤患者体内的药代动力学尚不完全明确。

分布

尚未对推荐剂量的硼替佐米在多发性骨髓瘤患者体内的分布容积进行研究。浓度为100—1000ng／ml时，硼替佐米与人体血浆蛋白的平均结合率为83％。

代谢

利用人体肝微粒体和互补脱氧核糖核酸(cDNA)表达的细胞色素P450同工酶进行的体外研究显示，硼替佐米主要通过细胞色素P450酶系的3A4、2D6、2C19、2C9和IA2酶氧化代谢。主要代谢途径是去硼酸化，形成2个去硼酸化代谢物，再通过羟基化形成几个代谢产物。去硼酸化的硼替佐米代谢产物无抑制26S蛋白酶体的活性。8名患者给药后10—30分钟的血浆数据显示，血浆中代谢产物的浓度比原形药物低。

消除

尚未对硼替佐米在人体内的消除途径进行研究。

特殊人群

年龄、性别和人种：尚未就年龄、性别和人种对硼替佐米药代动力学影响进行评价。

肝功能损害的患者：尚未进行对肝功能损害患者的药代动力学研究。

肾功能损害的患者：尚未进行对肾功能损害患者的药代动力学研究。临床研究中患者的肌酐清除率为13.8—220m1／min。

儿童：尚无儿童药代动力学资料。

适应症

本品用于多发性骨髓瘤患者的治疗，此患者在使用本品前至少接受过两种治疗，并在最近—次治疗中病情还在进展。

本品的有效性基于它的有效率。尚无临床对照试验证明其临床利益，如对存活率的改善。

成人
   
推荐剂量

本品的推荐剂量为单次注射1.3 mg／㎡，每周注射2次，连续注射2周(即在第1、4、日和11天注射)后停药10天(即从第12至第2l天)。3周为1个疗程，两次给药至少间隔72小时。

在临床研究中，被确认完全有效的患者再接受另外2个周期的注射用硼替佐米治疗。建议有效的患者接受8个周期的注射用硼替佐米治疗。

剂量调整以及重新开始治疗

当发生3级非血液学的或任何4级血液学的毒性(不包括下面讨论的神经病)时，应暂停本品治疗。一旦毒性症状得到缓解，可以重新开始本品的治疗，剂量减少25%(例如： 1.3mg／㎡降低到1.0mg／㎡；1.0mg／㎡降低到0.7mg／㎡)。如果患者发生与本品治疗有关的神经痛或周围感觉神经病，应按下表推荐的调整剂量进行治疗。如果患者本身患有严重的神经病，只有权衡利弊后方可使用本品。

Velcade

Generic name: bortezomib
Product Brand Name: Velcade
Product Manufacturer: Janssen-Cilag

Velcade description

What is Velcade?

Velcade having generic name bortezomib is used for the treatment of patients with multiple myeloma. It is also approved for the treatment of mantle cell lymphoma who have already received other treatments. In the year 2003, this drug was approved for the treatment of relapsed and refractory myeloma. Velcade is manufactured (made) by the Takeda Oncology Company – Millenium.


Use of Velcade in multiple Myeloma

The FDA of the United States Of America approved velcade for all the stages of illness related to myeloma. It is used throught the course of treatment starting from diagnose to first stage and beyond. Various studies have revealed that patients suffering from relapsed and refractory myeloma respond to the velcade therapy . Such therapy decreases the chances of disease worsening and also helps in improving survival. This drug has also shown good results among the patients who have previously received multiple previous therapies. The rate of response of this therapy is high and is much appreciated. In European region this drug is also approved for the patients who have already under gone any one therapy, including those patients who have already had stem cell transplant. In the present scenaria, this highly effective velcade is been studied in combination of other myeloma drugs.


Velcade mechanism of action

Velcade is basically a proteasome inhibitor. Proteasomes are the enzymes found in cells and play a vital role in cell function regulation and growth. It controls the breakdown of important proteins. Velcade works by blocking the activity of proteasomes there by restricting the process related to survival and growth of cancer cells. It has also been profounded that velcade can improve the bone disease in velcade patients. It is also safe in patients with myeloma related kidney damage as in patients with normal kidney function.


Untreated Myeloma

The drug was successfully approved only after its effective ness when used in combination with oral melphalan and prednisone. Velcade, in this combination is given for nine 6-week treatment cycles. Each treatment consists of 11 days of therapy and 10 day rest period. Velcade is given at a dose of 1.3mg /m2 twice a week during the first four week of treatment and for the rest of 5 cycles, the dose is given at the rate of 1.3mg /m2 once in a week. In case if the patient is taking different combination therapy then the number of treatment cycles may vary. Typically a total of eight cycles therapy is given for relapsed or refractory myeloma. After the proposed cycle, the treatment can be continue for the same or maintainance schedule. For maintainance it is generally given once a week for 4 weeks followed by a rest of 13 days.


How long is the Velcade treatment

Again the length or duration of the velcade treatment depends upon the type of therapy and the conbination of drug the patient is taking. It also depends upon the margin of side effects. Two additinal cycles are given after th complete response of the treatment.


Side effects of Velcade

If the side effects of velcade therapy occurs, then the doctor stops the treatment or temporarily lowers down the dose of drug. After the side effects are over the patient can be given the treatment of velcade but at a reduce level of 25%. The side effects generally includes low number of white blood cells, low platelet counts, diarrhoea, nausea, anaemia, fatigue, nerve pain, low potassium levels, burning, tingling, fever, loss of appetite, vomiting and low count of red blood cells.



Velcade notes:

Velcade generic name bortezomib is a medication which interferes with the growth of cancer cells and restricts them from spreading in the body. Velcade combined chemotherapy is used to treat multiple myeloma and mantle cell lymphoma.

Velcade side effects includes back, bone, or joint pain, constipation, diarrhea, dizziness, headache; lightheadedness, loss of appetite, nausea, stomach pain or upset, tiredness, trouble sleeping, vomiting, weakness, impaired thinking or reactions. It should not be used if allergic to bortezomib, mannitol, or boron.

Velcade can lower blood cells that help body to fight against infections. This makes bleeding from an injury easy or patient can get sick from others who are ill. Avoid being near to people who have colds, flu or other contagious illnesses.

This medication taken along with antifungal drugs (clotrimazole, itraconazole), antidepressant drugs
(nefazodone, paroxetine) or barbiturate (amobarbital, butabarbital) may effect its performance.

The mechanism of action of bortezomib combination therapy with activation of PKC-d can enhance the therapeutic effect of bortezomib providing a unique opportunity to overcome resistance to conventional chemotherapy.

Velcade can cause harm to an unborn baby. It is recommended not to consume Velcade without consulting doctor if you are pregnant. Use an effective form of birth control, and tell doctor if you become pregnant during treatment.

The dose and frequency of administration should be consistent with the Velcade package insert.

The average wholesale price of bortezomib for one 3.5-mg vial is $1094.

Store unopened vials in original package at room temperature (77 degrees F or 25 degrees C).