【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。
【适应证】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。
【用法与用量】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。

【原产地英文商品名】TARGRETIN
【原产地英文药品名】bexarotene capsules
【中文参考商品译名】塔革雷汀
【包装规格】75毫克/胶囊, 100胶囊/瓶
【生产厂家英文名】Ligand Pharmaceuticals
【临床试验期:完成
【中文适应病症】皮肤T淋巴细胞瘤
【产地国家】美国
【中文适应病症癌症

Targretin（bexarotene）

What is bexarotene ?

Bexarotene is used to treat skin lesions of cutaneous T-cell lymphoma (CTCL) in patients who have not responded to or not tolerated other therapies.

Bexarotene may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Targretin (bexarotene)?

Avoid prolonged exposure to sunlight or artificial ultraviolet light (e.g. sunlamps). Bexarotene may increase the sensitivity of your skin to sunlight. Use a sunscreen and wear protective clothing when exposure to the sun is unavoidable. Do not take bexarotene if you are pregnant or if you could become pregnant. Bexarotene is in the FDA pregnancy category X. This means that bexarotene will cause birth defects in an unborn baby. You must take a pregnancy test and have negative results within one week before starting treatment with bexarotene, and a pregnancy test should be repeated monthly during treatment. Bexarotene should be started on the second or third day of a normal menstrual period. Also, you will need to use two reliable forms of birth control at the same time for one month before starting treatment with bexarotene, during treatment with bexarotene, and for at least 1 month following the end of your treatment. If you become pregnant, stop using birth control, or miss your menstrual period, immediately stop taking bexarotene and notify your doctor. Men taking bexarotene with sexual partners who are pregnant, possibly pregnant, or who could become pregnant, must use condoms during sexual intercourse while using bexarotene and for at least one month after the last dose of bexarotene. Swallow each capsule whole. Do not chew them, dissolve them in liquid, or allow them to dissolve in your mouth.

Your doctor will want to monitor the levels of lipids (triglycerides and cholesterol) and thyroid hormones in your blood periodically during treatment with bexarotene. Treatment may be necessary if your cholesterol or triglyceride levels become elevated, or if your thyroid hormone levels are low.

Grapefruit and grapefruit juice may interact with bexarotene. The interaction could have potentially dangerous effects. Discuss the use of grapefruit and grapefruit juice with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.

What should I discuss with my healthcare provider before using Targretin (bexarotene)?

Do not take bexarotene without first talking to your doctor if you

• are allergic to other retinoids such as isotretinoin (Accutane), acitretin (Soriatane), etretinate (Tegison), or tretinoin (Vesinoid);

• have or ever have had pancreatitis (inflammation of the pancreas);

• have high triglyceride levels in your blood;

• have diabetes mellitus;

• have or ever have had gall bladder disease;

• have or ever have had liver disease;

• regularly drink alcohol;

• are taking gemfibrozil (Lopid);

• are taking any prescription medication especially for fungal infections, bacterial infections, diabetes, or seizures; or,

• eat grapefruit or drink grapefruit juice.

You may not be able to take bexarotene, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions, or are taking any of the medications listed above.

Do not take bexarotene if you are pregnant or if you could become pregnant. Bexarotene is in the FDA pregnancy category X. This means that bexarotene will cause birth defects in an unborn baby. You must take a pregnancy test and have negative results within one week before starting treatment with bexarotene, and a pregnancy test should be repeated monthly during treatment. Bexarotene should be started on the second or third day of a normal menstrual period. Also, you will need to use two reliable forms of birth control at the same time for one month before starting treatment with bexarotene, during treatment with bexarotene, and for at least 1 month following the end of your treatment. If you become pregnant, stop using birth control, or miss your menstrual period, immediately stop taking bexarotene and notify your doctor. Men taking bexarotene with sexual partners who are pregnant, possibly pregnant, or who could become pregnant, must use condoms during sexual intercourse while using bexarotene and for at least one month after the last dose of bexarotene. It is not known whether bexarotene passes into breast milk. Do not take bexarotene without first talking to your doctor if you are breast-feeding a baby.

How should I use bexarotene ?

Take bexarotene exactly as directed by your doctor. If you do not understand these instructions, ask your pharmacist, nurse, or doctor to explain them to you.

Your doctor will tell you how many bexarotene capsules to take each day. Take your daily dose of bexarotene all at once. Take bexarotene once a day with or immediately following a meal. Swallow each capsule whole. Do not chew them, dissolve them in liquid, or allow them to dissolve in your mouth. Do not take any bexarotene capsules after the expiration date printed on the label.

If any bexarotene capsules are broken or leaking, do not touch the capsules or the contents and notify your pharmacist immediately. If the contents of a broken capsule get on your skin, immediately wash the area with soap and water and notify your physician.

Your doctor will want to monitor the levels of lipids (triglycerides and cholesterol) and thyroid hormones in your blood periodically during treatment with bexarotene. Treatment may be necessary if your cholesterol or triglyceride levels become elevated, or if your thyroid hormone levels are low.

It may take many weeks of treatment to see the effects of this drug. Do not stop taking bexarotene if you do not see results immediately. Some patients treated with bexarotene see improvement within the first several weeks of treatment, however most patients require several months or more of treatment to improve.

Store bexarotene at room temperature away from moisture and heat. Keep this product out of the reach of children.

What happens if I miss a dose?

Take the missed dose, with food, as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take only your next regularly scheduled dose. Do not take a double dose of this medication.

What happens if I overdose?

Seek emergency medical attention.

Symptoms of a bexarotene overdose are unknown.

What should I avoid while using bexarotene ?

Avoid prolonged exposure to sunlight or artificial ultraviolet light (e.g. sunlamps). Bexarotene may increase the sensitivity of your skin to sunlight. Use a sunscreen and wear protective clothing when exposure to the sun is unavoidable.

Vitamin A may increase side effects when taking bexarotene. Limit your use of vitamin A supplements to not more than the recommended daily allowance (RDA) of 4000 to 5000 International Units (IU) a day. If you take vitamins, check the label to see how much vitamin A they contain. If you are not sure, ask your doctor or pharmacist.

Grapefruit and grapefruit juice may interact with bexarotene. The interaction could have potentially dangerous effects. Discuss the use of grapefruit and grapefruit juice with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.

Bexarotene side effects

If you experience any of the following serious side effects, stop taking bexarotene and seek emergency medical attention:

• an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives); or

• symptoms of pancreatitis (inflammation of the pancreas) such as persistent nausea, vomiting, and abdominal or back pain.

Other, less serious side effects may be more likely to occur. Continue to take bexarotene and talk to your doctor if you experience:

• an increase in fats in the blood (blood lipids) such as cholesterol or triglycerides (blood tests will detect this);

• a underactive thyroid (blood tests will detect this);

• blood problems;

• headache;

• fatigue;

• weakness or loss of strength;

• swelling;

• rash;

• dry skin;

• infections;

• nausea; or

• diarrhea.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088。