部份中文艾比特思处方资料（仅供参考）
药品英文名
Cetuximab
药品别名
艾比特思、西妥昔单抗，ERBITUX、C-225
药物剂型
西妥昔单抗注射剂：100mg/50ml/瓶(西妥昔单抗浓度为2mg/ml，8.48mg/ml氯化钠，1.88mg/ml磷酸氢二钠七水合物，0.42mg/ml磷酸二氢钠一水合物，注射用水)。2～8℃冰箱冷藏，不能冷冻。
本品溶液打开后，2～8℃冰箱冷藏能存放12h，20～25℃室温存放仅8h。
药理作用
本品由哺乳动物(鼠骨髓瘤)作细胞培养产生，是人和嵌合体鼠的单克隆抗体的重组体，由小鼠股静脉内抗表皮生长因子的抗体与人体重链和轻链恒定区的免疫球蛋白G1组成。
本品可特异性地与正常和肿瘤细胞的表皮生长因子受体(epidermalgrowth factor receptor，EGFR)相结合，竞争性抑制表皮生长因子受体与其他配体如转化生长因子α的结合。本品与生长因子受体的结合阻断磷酸化作用和与受体相关联激酶的活性，抑制细胞生长，诱导细胞凋亡，并减少基质金属蛋白酶和血管内皮生长因子的产生。
表皮生长因子受体是跨膜糖蛋白，属于Ⅰ型受体酪氨酸激酶，Ⅰ型受体酪氨酸激酶包括表皮生长因子HER1、HER2、HER3和HER4。表皮生长因子受体不断由正常上皮组织如皮肤和毛囊上皮组织所表达出来，在结肠癌和直肠癌患者体内可检测到过度表达的表皮生长因子受体。动物体内外试验表明，本品可抑制肿瘤细胞的存活和生长从而抑制表皮生长因子受体的过度表达。动物试验表明在依立替康或依立替康与5-氟尿嘧啶合用的基础上加用本品比单纯用其化疗抗肿瘤的效果好。
药动学
本品单独使用、与其他抗肿瘤药物或放疗同时使用时药代动力学均呈非线性过程。给药剂量20～400mg/m2范围内，本品的药时曲线下面积(AUC)增大比例高于药量增加比例；给药剂量20～200mg/m2范围内，清除率(CL)从0.08L/(m2·h)下降到0.02L/(m2·h)；给药剂量超过200mg/m2后，CL不再改变。
本品表观分布容积(Vd)为45.2～61.9ml/kg，约相当于血浆体积，且不随给药剂量变化。2h内静滴本品400mg/m2，峰浓度(Cmax)平均为184μg/ml(92～327μg/ml)，消除半衰期平均为97h(41～213h)；1h内静滴本品200mg/m2，Cmax平均为140μg/ml(120～170μg/ml)；按推荐剂量(起始剂量400mg/m2，每周维持剂量250mg/m2)，3周血药浓度达稳态，Cmax平均为168～235μg/ml，谷浓度(Cmin)平均为41～85μg/ml，半衰期平均为114h(75～188h)。
适应证
用于结肠直肠癌：与依替立康合用于依替立康化疗无效的患者；单独使用，用于不能耐受依替立康的患者。多种标准化疗药物的联合方案对晚期非小细胞肺癌(NSCLC)具有潜在疗效。
禁忌证
1.对本品过敏者禁用。
2.儿童应用的安全性和疗效未知，不适用儿童。
3.生殖毒性分级为C级，孕妇应用是否会引起胚胎严重伤害或影响生殖能力尚不清楚，本品不适用于孕妇。
4.本品是否经乳汁分泌尚不清楚，但人类IgG1经乳汁分泌。由于本品半衰期长达114h，故哺乳期妇女停用本品60天后方可哺乳。
注意事项
1.光照能加重皮肤反应，使用本品时建议戴遮光帘或帽子，以减少光照。2.如果患者发生轻、中度(1级、2级)输液反应，则输液速率应减小50%。如发生严重的输液反应(3级、4级)，应立即终止使用。
3.轻、中度皮肤毒性改变不需要做剂量的调整。
4.如果患者出现急性痤疮样皮疹，应停止输液1～2周；若症状改善，本品剂量可适当降低；多次出现急性痤疮样皮疹应停止用药。
5.不要将本品静脉推注。
6.本品禁止振动和稀释。
7.在本品输液过程中应准备必要的药物治疗可能发生的严重的输液反应。
8.慎用：对鼠类蛋白过敏者慎用。
不良反应
最严重的不良反应有输液反应(3%)，皮肤毒性(1%)，间质性肺疾病(0.5%)，发热(5%)，败血症(3%)，肾衰(2%)，肺栓塞(1%)，脱水(本品与依立替康联合应用时发生率为5%，本品单独应用时发生率为2%)，腹泻(本品与依立替康联合应用时发生率为6%，单独应用时未发现)；共有10%接受本品与依立替康联合治疗和5%接受本品单独治疗的患者由于不良反应而终止用药。本品与依立替康联合治疗患者不良反应的发生情况为：痤疮样皮疹88%、虚弱/不适73%、腹泻72%、恶心55%、腹痛45%、呕吐41%。接受本品单独治疗患者不良反应的发生情况为：痤疮样皮疹90%、虚弱/不适49%、腹泻33%、恶心29%、腹痛28%、呕吐28%。约5%患者对本品产生抗体。
用法用量
静滴：本品可由输液泵或注射器泵输入体内，与依立替康联合应用或单独应用的推荐剂量为首次负荷剂量(第一次注射剂量)400mg/m2，120min静滴(最大滴注速率为5ml/min)；每周维持剂量(其他时间注射剂量)250mg/m2，超过60min静滴(最大滴注速率为5ml/min)。建议术前用H1受体拮抗剂(如50mg苯海拉明静脉注射)。
药物相应作用
本品与依立替康合用无意外事件发生和药代动力学相互作用。
Indications
Head & Neck Cancer:
ERBITUX® (cetuximab), in combination with radiation therapy, is indicated for the initial treatment of a certain type of locally or regionally advanced head and neck cancer.
ERBITUX, in combination with platinum-based chemotherapy with 5-fluorouracil, is indicated for the initial treatment of patients with a certain type of head and neck cancer whose tumor has returned in the same location or spread to other parts of the body.
ERBITUX is also indicated for use alone to treat patients with a certain type of head and neck cancer whose tumor has returned in the same location or spread to other parts of the body and whose disease has progressed following platinum-based chemotherapy.
Colorectal Cancer:
ERBITUX is indicated for the treatment of patients who have colorectal cancer that has spread to other parts of the body and whose tumor expresses a protein called an Epidermal Growth Factor Receptor (EGFR). Treatment with ERBITUX is given in the following two ways:
■As a single agent:
for patients whose disease has progressed after receiving both irinotecan and oxaliplatin
for patients who are unable to tolerate chemotherapy with irinotecan
■In combination with another chemotherapy drug, irinotecan, for
patients whose disease has progressed after receiving chemotherapy with irinotecan. The effectiveness of ERBITUX in this combination is based on data regarding patients in clinical studies whose tumors became smaller. At present, there is no proof in this setting that ERBITUX improves the symptoms that a patient feels or helps a patient live longer
The results of certain clinical trials of patients with advanced or metastatic colorectal cancer were reviewed. It was found that
ERBITUX did not work in patients whose tumors had mutations of the K-ras gene.
ERBITUX is not recommended for the treatment of patients whose colorectal cancer tumors have mutations of the K-ras gene.
ERBITUX is available by prescription only.
Important Safety Information including Boxed WARNINGSAllergic Reaction
■Severe allergic reactions due to ERBITUX® (cetuximab) therapy have occurred in 42 of 1373 patients (3%) receiving ERBITUX during clinical studies, resulting in death in less than 1 in 1000 patients
Symptoms can include trouble with breathing (including tightening of the airways, wheezing, or hoarseness), low blood pressure, shock, loss of consciousness, and/or heart attack
Most (90%) of the severe allergic reactions occurred with the first dose of ERBITUX, although some patients experienced their first severe allergic reaction during a subsequent dose of ERBITUX
Your doctor or nurse should watch you closely for these symptoms during treatment and may need to stop therapy in the event of an allergic reaction
Severe allergic reactions require that treatment with ERBITUX be stopped immediately and not started again
Heart Attack
■Heart attack and/or sudden death occurred in 4 of 208 patients (2%) with head and neck cancer treated with radiation therapy and ERBITUX (cetuximab) as compared to none of 212 patients treated with radiation therapy alone
■Heart problems resulting in death and/or sudden death occurred in 7 of 219 patients (3%) with head and neck cancer treated with platinum-based chemotherapy with 5-fluorouracil and cetuximab compared to 4 of 215 patients (2%) treated with chemotherapy alone, based on a study conducted in Europe using European cetuximab
■Notify your doctor if you have a history of any heart disease
Lung Disease
■Lung disease, which resulted in 1 death, occurred in 4 of 1570 patients (<0.5%) receiving ERBITUX in several clinical trials in colorectal cancer and head and neck cancer Notify your doctor if you develop shortness of breath while receiving ERBITUX
ERBITUX treatment should be stopped if symptoms worsen or lung disease is confirmed
Skin Problems
■In several clinical trials in colorectal cancer and head and neck cancer with ERBITUX, skin problems including an acne-like rash, skin drying and cracking, infections (including infections of the blood, skin, eyes, and lips), and abnormal hair growth were seen Sun exposure may worsen these effects
Patients taking ERBITUX should wear sunscreen and hats to limit sun exposure
A related nail disorder that causes painful swelling of the skin around the nails—most often of the large toes and thumbs—also was reported
Notify your doctor if you develop any of these symptoms while receiving ERBITUX
ERBITUX With Chemotherapy and Radiation
■Death and serious heart problems were seen in a clinical trial that studied the combination of ERBITUX, radiation therapy, and cisplatin (a cancer drug) treatment in patients with head and neck cancer Two out of 21 patients died and four patients stopped treatment due to side effectsThe safety and effectiveness of this regimen has not been established
Electrolyte Depletion
■Low levels of magnesium and accompanying low calcium and potassium levels have been reported with ERBITUX when given by itself and in combination with other cancer drugs Your doctor or nurse should periodically monitor your blood electrolyte levels and administer intravenous replacement as needed
Late Radiation Side Effects
■The percentage of late radiation side effects was higher in patients given ERBITUX with radiation therapy compared with patients given radiation therapy alone The following sites were affected: organs that produce saliva(65%/56%), voice box (52%/36%), tissue below the skin (49%/45%), lining of the mouth and some organs (48%/39%), food pipe (44%/35%), and skin (42%/33%) in the patients given ERBITUX and radiation versus patients given radiation alone, respectively
■The percentage of severe late radiation side effects was similar among patients given radiation therapy alone and patients given ERBITUX plus radiation therapy
Pregnancy and Nursing
■Notify your doctor if you are pregnant or if you become pregnant while receiving ERBITUX. Contraception must be used, in both males and females, during ERBITUX therapy and for six months following the last dose of ERBITUX. ERBITUX may be passed from the mother to the developing fetus, and may cause harm to the fetus.
ERBITUX should only be used during pregnancy if the potential benefit is greater than the potential risk to the fetus
■ERBITUX may be passed through human breast milk. Because of the potential for serious side effects in nursing infants from ERBITUX, nursing is not recommended during ERBITUX therapy and for two months following the last dose of ERBITUX
Additional Side Effects
In studies of ERBITUX:
■The most serious side effects associated with ERBITUX across all clinical studies were: allergic reactions, heart attack, skin problems, skin irritation in the radiation area, infection, kidney failure, lung disease, and blood clots in the lung
■The most frequent side effects associated with ERBITUX (reported in at least 25% of patients) are skin problems (including rash, itching, and nail changes), headache, diarrhea, and infectionIn a study of ERBITUX and radiation therapy given to 208 people with head and neck cancer versus radiation therapy alone given to 212 people with head and neck cancer:
■The most frequent side effects were: acne-like rash (87% versus 10%), skin irritation in the radiation area (86% versus 90%), weight loss (84% versus 72%), and feeling weak (56% versus 49%)
■Serious side effects reported by at least 10% of patients that received ERBITUX in combination with radiation therapy versus radiation therapy alone included: skin irritation in the radiation area (23% versus 18%), acne-like rash (17% versus 1%), and weight loss (11% versus 7%)In a study of European cetuximab in combination with platinum-based chemotherapy with 5-fluorouracil given to 219 people with head and neck cancer versus chemotherapy alone given to 215 people with head and neck cancer:
■The most frequent side effects were: acne-like rash (70% versus 2%), nausea (54% versus 47%), and infection (44% versus 27%).
■Serious side effects reported by at least 10% of patients in either arm were: infection (11% versus 8%).
■ERBITUX yields approximately 22% higher blood levels of cetuximab relative to European cetuximab. It is possible that U.S. patients receiving ERBITUX may experience more frequent or severe side effects than patients in the study conducted in Europe. In a study where ERBITUX and supportive care were given to 288 people with metastatic colorectal cancer:
■The most frequent side effects reported were: feeling tired (89%), rash or shedding of the outer layer of the skin (89%), stomach pain (59%), and other pain (51%)
■Serious side effects reported by at least 10% of patients included: fatigue (33%), other pain (16%), shortness of breath (16%), stomach pain (14%), infection without abnormal decrease in white blood cell count (13%), rash or shedding of the outer layer of skin (12%), and other intestinal problems (10%)In studies where ERBITUX and irinotecan were given to 354 people with metastatic colorectal cancer:
■The most frequent side effects reported were: acne-like rash (88%), feeling weakness or discomfort (73%), diarrhea (72%), and nausea (55%)
■Serious side effects reported by at least 10% of patients included: diarrhea (22%), decrease in white blood cell count (17%), feeling weakness or discomfort (16%), and acne-like rash (14%)
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20113920485716.pdf