NEXAVAR(SORAFENIB TOSYLATE)TABLET ORAL是近10多年来唯一被FDA批准的用于治疗肾癌及肝细胞癌的新药”
多吉美（索拉非尼 sorafenib）片剂，薄膜包衣口服使用
美国首次批准：2005
目前的主要变化
适应症和用法，肝细胞癌 11/2007
警告和注意事项，
与多西他赛的相互作用 11/2007
与多柔比星互动 11/2007
肝损伤 11/2007
适应症和用法
多吉美是用于治疗所示的激酶抑制剂
不能切除的肝细胞癌
晚期肾细胞癌
用法用量
400毫克（2片），口服，每日两次，没有食物。
中断治疗和/或减少剂量可能需要管理可疑的药物不良反应。剂量可以减少到400 mg，每天一次或至400mg隔日1次。
剂型和规格
200毫克片剂（参见图3）
禁忌
多吉美患者中禁忌与已知的严重过敏索拉非尼或多吉美的任何其他组件。
警告和注意事项
心肌缺血和/或梗死，可能会发生。多吉美考虑暂时或永久终止。
可能会发生出血。如果出血就必须的医疗干预，多吉美考虑停药。
高血压通常发生在治疗的过程中早期，并与抗高血压疗法管理。在第一6周监测血压每周一次，然后定期和治疗，按要求。
手足皮肤反应和皮疹是常见的。管理层可能包括局部治疗缓解症状，暂时中断治疗和/或调整剂量，或在严重或持续的情况下，永久终止。
胃肠穿孔是一种罕见的不良反应。在胃肠道穿孔的情况下，多吉美治疗应停药。
多吉美治疗的暂时中断，建议在发生重大外科手术的病人。
注意事项时，建议同时给予物质代谢/由UGT1A1途径主要是消除（如伊立替康）。
当共同给予多西他赛注意事项建议。
注意事项时，建议同时给予阿霉素
当给予孕妇多吉美可能对胎儿造成伤害。育龄妇女应尽量避免怀孕，而在多吉美。
不良反应
最常见的不良反应（≥20％），这被认为是与多吉美，是疲劳，体重减轻，皮疹/脱屑，手足皮肤反应，脱发，腹泻，厌食，恶心，腹痛。
药物相互作用
UGT1A1（例如伊立替康）和UGT1A9基板：注意，药物的AUC增加时共同施用多吉美。
多西他赛：小心，多西紫杉醇AUC增加时，共给予多吉美。
多柔比星：小心，阿霉素AUC增加时，共给予多吉美。
氟尿嘧啶：注意，当共同施用多吉美氟尿嘧啶AUC变化。
CYP2B6和CYP2C8底物：注意，预期的全身性暴露，以增加当共同施用多吉美。
CYP3A4诱导剂：预计将增加索拉非尼的代谢，降低索拉非尼的浓度。
特殊人群中使用
肝损害：无需调整剂量是必要的肝癌患者Child-Pugh分级A和B肝受损。多吉美尚未研究的患者儿童Pugh C级肝功能损害。
肾损害：多吉美尚未研究在接受透析的病人。
完整说明书附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b50667e4-5ebc-4968-a646-d605058dbef0
TIPS TO REMEMBER: Nexavar
Patients taking concomitant warfarin should be monitored regularly for changes in prothrombin time, INR, or clinical bleeding episodes.
Blood pressure should be monitored weekly during the first six weeks of Nexavar therapy and managed throughout treatment.
Temporary or permanent discontinuation of Nexavar therapy should be considered in those with cardiac ischemia and/or infarction.
When dose reduction is necessary, the dose may be reduced to 400 mg taken once daily. If further dose reduction is required, the dose can be reduced to a single 400-mg dose taken every other day.
For the first time in more than 10 years, the Food & Drug Administration has granted marketing approval to a drug for kidney cancer. Sorafenib (Nexavar, Bayer/ Onyx) was recently approved for the treatment of advanced renal cell carcinoma, the most common form of the disease. Sorafenib is currently available through specialty pharmacies.
Sorafenib is the first oral multi-kinase inhibitor that targets serine/ threonine and receptor tyrosine kinases in both the tumor cell and the tumor vasculature, said Ronald Bukowski, M.D., director of experimental therapeutics at the Cleveland Clinic Taussig Cancer Center in Ohio. In preclinical models, sorafenib targeted members of two classes of kinases, including RAF kinase, VEGFR-2, VEGFR-3, PDGFR-B, KIT, and FLT-3. These kinases are known to be involved in both tumor cell proliferation and tumor angiogenesis.
Nexavar
According to the manufacturer, sorafenib was approved based on data from the largest randomized, placebo-controlled clinical trial ever conducted in patients with advanced renal cell carcinoma. Compared with placebo, sorafenib was found to double the time of progression-free survival. The maker also reported that a recent interim analysis showed sorafenib reduced mortality risk by 28%.
The most common adverse events associated with sorafenib in clinical trials were diarrhea, rash/ desquamation, fatigue, blisters on the palms of the hands and soles of the feet, alopecia, nausea, pruritus, hypertension, vomiting, and anorexia. Bukowski said that in early-stage clinical trials, grades 3 and 4 adverse events were rare, occurring in probably less than 5% of patients.
Sorafenib should be used with caution when taken concomitantly with drugs eliminated primarily by the UGT1A1 pathway, such as irinotecan (Camptosar, Pfizer). In addition, the manufacturer said, exercise caution when administering sorafenib concomitantly with doxorubicin and substrates of CYP2B6 and CYP2C8. The company noted that sorafenib has not been tested in those with Child-Pugh C hepatic impairment, although no dose adjustment is necessary in those with Child-Pugh A or B hepatic impairment.
Sorafenib is classified as Pregnancy Category D, so adequate contraception during treatment and for at least two weeks after discontinuation of therapy is recommended for male and female patients. Women should be advised against breastfeeding while taking sorafenib. The recommended daily dose of sorafenib is 400 mg taken twice daily (2 x 200 mg tablets), without food, at least one hour before or two hours after eating.
Sorafenib is in phase III clinical trials for the treatment of advanced hepatocellular carcinoma and metastatic melanoma. A phase III clinical trial for non-small-cell lung cancer is planned for the first half of this year.
--------------------------------------------------------------
附件：
20082501003511.pdf
