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英文药名: Targretin（Bexarotene Capsules）
中文药名: 蓓萨罗丁胶囊,贝沙罗汀
药品介绍
【商品名】Targretin
【通用名】Bexarotene
【化学名】4-[1-(5，6，7，8-四氢-3，5，5，8，8-五甲基-2-萘基）乙烯基]苯甲酸
【上市厂商】由美国Ligand制药公司研制，2000年1月15日在美国首次上市。
【适应症】用于口服治疗顽固性皮肤T-细胞淋巴瘤的皮肤症状。
【药理作用】本品可选择性地结合并激活视黄酸类（retinoid）X受体亚型（RXRα，RXRβ，RXRγ）。RXR可与多种受体[如维A酸受体（RAR）、维生素D受体、甲状腺素受体，以及过氧化物酶体增生物激活受体（PPAR）]形成异二聚体。这些受体一旦被激活可控制基因的表达，控制细胞分化和增生。在体外试验中，本品可抑制某些肿瘤细胞系的生长；在动物模型体内试验中，本品可诱使乳腺瘤消退。
本品口服后，约2小时达血浆峰浓度，半衰期约为7小时。含脂食物可增加本品吸收，较之葡萄糖溶液，含脂食物可使300mg本品的AUC及Cmax分别上升35%和48%；本品可与血浆蛋白高度结合（99%）。
在血浆中能测得本品的四种代谢产物：6-和7-羟基bexarotene以及6-和7-氧代bexarotene。体外试验显示细胞色素P450 3A4是对氧化产物形成及氧化产物葡糖醛酸化起主要作用的酶。
经对Ⅱ型糖尿病患者进行本品及本品代谢物肾消除过程的检测，目前认为本品主要大部分随胆汁消除，基本不随尿液排出。
【临床评价】两项开放性研究显示本品对早期及晚期难治性皮肤T-细胞淋巴瘤有效。
在第一项研究中，对至少两种治疗方法无反应或不能耐受的早期皮肤T-细胞淋巴瘤病人服用本品一日300mg/m2后，28例病人中有15例（54%）获得全部或部分反应（改善至少达50%以上），而更高剂量组反应率为10例/15例（67%），此外，一日300mg/m2组中有2例病人在25周内复发。
在第二项研究中，94例至少一种全身性治疗方法无效的晚期皮肤T-细胞淋巴瘤病人中，56例接受本品一日300mg/m2后有25例（45%）获得反应，另外35例接受较高剂量本品，有21例（55%）获得瓜；低剂量组有反应的病人中有9例经中位时间19周复发。
在两项研究中，共有84例病人接受本品一日300mg/m2，其中3例（4%）获得完全反应，40例（48%）获得部分瓜；在高剂量组中，完全反应率为9例/53例（17%）。
【不良反应】
本品的多数不良反应与剂量有关，使用本品后大部分病人会出现高甘油三酯血症、高胆固醇血症及高密度脂蛋白水平低下，通常需要对症治疗或减少本品的用药剂量；此外，尚易发生中枢性甲状腺机能减退并需要治疗，还常发生头痛、虚弱、白细胞减少、贫血、感染、皮疹、光敏反应和脱发。临床研究中约30%的病人停药；亦有转氨酶升高、致命性胰腺炎和致命性胆汁郁积的报道。
【注意事项】
本品可对胎儿造成伤害，故孕妇禁用。
在动物试验中本品可致睾丸萎缩。
本品理论上与P450 3A4诱导剂或抑制剂可发生相互作用；已发现经P450 3A4代谢的吉非贝齐（gemfibrozil）可升高本品血浆浓度，这至少部分归因于吉非贝剂能抑制细胞色素P4503A4；本品与胰岛素、磺酰脲类、二甲双胍、曹格列奈或噻唑烷二酮（格列酮）类药物合用时可致低血糖。由于本品是一种VA衍生物，与VA合用可增加药物的毒性作用。
对bexarotene或该产品的其他成分过敏者禁用。
【用法用量】治疗皮肤T-细胞淋巴瘤的推荐剂量为一日300mg/m2，与食物同服；若8周后尚未见疗效，则可增加剂量至一日400mg/m2，最佳治疗时间目前尚未确定。
【剂型规格】本品为75mg口服明胶软胶囊制剂。
Targretin® (bexarotene) capsules
Targretin® (bexarotene) capsules 75 mg are used to treat the skin problems arising from a disease called cutaneous T-cell lymphoma (CTCL) when at least one systemic therapy has not worked. A doctor must advise on the proper use of Targretin capsules.
CTCL is a rare disease. In CTCL, T-cells become cancerous and affect the skin and the blood. Normally T-cells are used by the body to fight infections. CTCL symptoms are often mistaken for a rash, eczema or psoriasis.
In the United States, there are nearly 2,000 new cases annually and the annual incidence continues to rise and its cause is unknown.
Do not take Targretin capsules if you are pregnant or plan to become pregnant.
Targretin capsules may harm your fetus (unborn baby). You should contact your doctor immediately if you believe or suspect you are pregnant while you are taking Targretin capsules and until one month after you stop taking Targretin capsules.
If you are capable of becoming pregnant, you must have a pregnancy test within one week before you start Targretin capsule therapy and monthly while you are on therapy, confirming you are not pregnant.
You must use effective contraception (birth control) continuously starting one month before beginning treatment with Targretin capsules until one month after you stop taking Targretin capsules. It is strongly recommended that two reliable forms of contraception be used together. At least one of these two forms of contraception should include condoms, diaphragms, cervical caps, IUDs, or spermicides.
If you are male and your partner is pregnant or capable of becoming pregnant, you should discuss with your doctor the precautions you should take.
Do not take Targretin capsules if you are allergic to this medicine.
Targretin capsules can greatly increase blood levels of lipids (triglycerides and cholesterol) and these levels must be monitored and, if elevated, treated.
Targretin capsules can cause an underactive thyroid and periodic blood tests will be needed to detect this. Medication to control the condition may be necessary.
Before you start to take Targretin capsules, tell your doctor if you are pregnant, have or previously had an inflamed pancreas (pancreatitis), are breastfeeding, are taking gemfibrozil (Lopid®) a medicine to reduce high triglyceride cholesterol (fats) levels in the blood, or are taking tamoxifen (Nolvadex®).
You should tell your doctor if you are allergic to retinoid medications (for example: Accutane® [isotretinoin], Soriatane® [acitretin], Tegison [etretinate], Vesinoid® [tretinoin]), have or ever had high triglyceride (a fatty substance) levels in your blood, diabetes mellitus (sugar diabetes), gall bladder disease, any liver disease, if you regularly drink more than a small amount of alcohol, are taking any prescription medication for fungal infections, bacterial infections, or seizures, or eat a lot of grapefruit or drink a lot of grapefruit juice.
Because vitamin A in large doses may cause some side effects which are similar to those seen in patients applying Targretin gel, do not take more than the recommended daily dietary allowance of vitamin A (4000 to 5000 International Units). If you are not sure, ask your doctor or pharmacist.
Your skin may become more sensitive to sunlight while taking this medicine. Minimize exposure to sunlight and do not use a sunlamp.
The most common side effects with Targretin capsules are an increase in blood lipids (fats in the blood), headache, weakness, underactive thyroid, decreased white blood cells and diarrhea.
Please also see the Targretin capsules Full Prescribing Information and patient's instructions for use including Boxed WARNING and additional important safety information.
For more information about Targretin Capsules, visit www.Targretin.com or call Eisai Medical Services Oncology at (877) 873-4724. To report suspected adverse reactions, call (877) 873-4724.
FDA批准治疗皮肤T细胞淋巴瘤的口服药Targretin胶
FDA已经批准Targretin胶用于局部治疗对其他治疗不能耐受或没有反应的皮肤T细胞淋巴瘤。这种病变的一个初发症状是局部皮肤出现鳞屑、发痒进而剥脱，还会出现皲裂导致溃疡和感染。约有16，000美国人罹患此病，同时每年新发病者为1，000人。
皮肤T细胞淋巴瘤目前是一种不可治愈的慢性疾病，因其皮损部位难看、痒、痛而严重影响生活质量。Targretin胶属于视黄醛类，表现有限制某些皮肤癌生长的作用。视黄醛属于维生素A的同系物，其能够激活视黄酸和细胞核的视黄醛X受体，该受体的激活会触发一个化学信号链，启动抑制肿瘤发展的基因。但是科学家目前还不能完全解释药物抗肿瘤的机制。Targretin是选择性激活视黄醛X受体的唯一物质。圣地亚哥的Targretin 胶制造公司Ligand Pharmaceuticals去年11月份获得了FDA对Targretin胶囊的批准，这种口服药的获准是基于肿瘤药物咨询委员会对该药的有关研究进行审核基础之上的。在接受Targretin胶囊临床实验的病人中40％对该治疗有反应，皮损片数目减少。与以往的病例比较，发现后者中实际上没有皮损自行消失的病例。由于皮肤T细胞淋巴瘤较少见，制药公司难以收集病例，因而没有设立安慰剂对照组。
Targretin胶非常有效。休斯敦Anderson癌症中心的 Duvic 博士估计67％的病人可从该药获益，与口服胶囊相比，胶体更适于皮损面积不太大的患者，以及对系统治疗有效但仍有小块皮损的患者。早期皮肤T细胞淋巴瘤可局部涂抹视黄醛，没有治疗反应的可随之给以氨甲喋呤和干扰素，这两种药物都需静脉给药，并有相当多的副作用。 | 
