分类名称 一级分类：皮肤科用药 二级分类：常用抗麻风及麻风反应药物 三级分类：    药品英文名 Thalidomide 药品别名 反应停、沙立度胺、肽胺哌啶酮、酞胺哌啶酮、酞谷酰亚胺、酞咪哌啶酮、K-7、Thalidomidum  THALOMID CAP   药物剂型 片剂：25mg，50mg。 胶囊剂：50MG  100MG  200MG 药理作用 THD可抑制肿瘤坏死因子α(TNF-α)的产生，因而具有抗炎作用。THD也是一种强效的T细胞共刺激剂，可向T细胞提供活化信号，促进IL-2介导的细胞增殖和INF-γ表达，并与T细胞受体(TCR)复合物有协同作用，因而具有免疫调节作用。另外THD还有抗血管生成及致畸作用。本药为谷氨酸衍化物，具有镇静催眠、止痛止痒、退热等作用。对麻风反应疗效较好。其作用机制可能为抑制溶酶体酶、稳定溶酶体膜、抑制中性粒细胞的趋化。另外，本药尚有免疫抑制作用，可用于骨髓移植。 药动学 本药口服易吸收，缓释片的达峰时间为2.9～5.7h：咀嚼片为2～6h。本药总蛋白结合率高，分布容积为120L。本药可能经肝脏代谢，清除半衰期为5～7h。肾脏清除率为每分钟1.15ml，小于给药剂量的0.7%以原形从尿排出。少部分随粪便排出。 适应证 1.适用于各型麻风反应如发热、结节红斑、神经痛、关节痛、淋巴结肿大等，对结核样型的麻风反应疗效稍差。对麻风无治疗作用，可与抗麻风药同用以减少麻风反应。 2.可用于骨髓移植。 3.尚可治疗红斑狼疮、复发性发热性结节性非化脓性脂膜炎、日光性痒疹、多形性日光疹、结节性痒疹、带状疱疹、扁平苔藓、家族性良性天疱疮(家族性良性慢性天疱疮)、白塞病(Behcet病)、渗出性多形红斑(多形红斑)。 禁忌证 1.对本药过敏者。 2.孕妇尤以妊娠早期禁忌。 注意事项 1.育龄妇女在服药期间应避孕。 2.驾驶员及机器操作者慎用。 3.出现神经炎症状时应立即停药，以免造成不可逆病变。 不良反应 1.常见口干、口苦、恶心、呕吐、便秘、食欲缺乏、头昏、嗜睡、面部和四肢水肿、闭经、性欲减退、中毒性神经炎、心率减慢和皮疹等。严重者须停药并给予对症治疗。 2.偶见白细胞和血小板减少。 3.本品有强烈致畸作用，可引起“海豹肢”畸形，妊娠妇女禁用。 4.长期应用(总剂量40g以上)可致多发性神经炎。 用法用量 口服给药：每天100～200mg，分4次服用。对于严重麻风反应，可增至300～400mg(反应得到控制即可逐渐减量维持)。对长期反应，需要较长期服药，每天或隔日服用25～50mg。1.Ⅱ型麻风反应：开始每天200～400mg，症状控制后减至每天50～100mg维持。2.其他疾病：每天100～400mg，症状控制后减至每天25～50mg维持。 药物相应作用 与地塞米松合用，发生中毒性上皮细胞坏死溶解的危险性增加。 专家点评 本品为防治麻风反应的首选药，对麻风病本身无治疗作用，常与其他抗麻风药合用以减少麻风反应，对各型麻风病尤其是发热、结节红斑、神经疼痛和淋巴肿大有一定的疗效。近年发现本品有免疫抑制作用，可用于骨髓移植。THD对Ⅱ型麻风反应疗效良好，总有效率达99%，对Ⅰ型麻风反应疗效很差。THD对轻中度的移植物抗宿主病有较好疗效，对皮肤型的红斑狼疮亦有较好疗效，但对系统损害无效。THD是治疗复发性口疮的很好药物，对HIV感染合并的阿弗它溃疡有良好疗效。 THALOMID CAP 50MG B/P DS 280 (THALIDOMIDE) THALOMID CAP 50MG B/P DS 28 (THALIDOMIDE) THALOMID CAP 100MG B/P DS 28 (THALIDOMIDE) THALOMID CAP 200MG B/P DS 28 (THALIDOMIDE THALOMID CAP 100MG B/P DS 140 (THALIDOMIDE Thalomid (Thalidomide) Description Thalomid (Thalidomide) (thalidomide), α-(N-phthalimido) glutarimide, is an immunomodulatory agent. The empirical formula for thalidomide is CHNO and the gram molecular weight is 258.2. The CAS number of thalidomide is 50-35-1. Thalidomide is an off-white to white, odorless, crystalline powder that is soluble at 25°C in dimethyl sulfoxide and sparingly soluble in water and ethanol. The glutarimide moiety contains a single asymmetric center and, therefore, may exist in either of two optically active forms designated S-(-) or R-(+). Thalomid (Thalidomide) is an equal mixture of the S-(-) and R-(+) forms and, therefore, has a net optical rotation of zero. Thalomid (Thalidomide) is available in 50 mg, 100 mg, 150 mg and 200 mg capsules for oral administration. Active ingredient: thalidomide. Inactive ingredients: pregelatinized starch and magnesium stearate. The 50 mg capsule shell contains gelatin, titanium dioxide, and black ink. The 100 mg capsule shell contains black iron oxide, yellow iron oxide, titanium dioxide, gelatin, and black ink. The 150 mg capsule shell contains FD&C blue #2, black iron oxide, yellow iron oxide, titanium dioxide, gelatin, and black and white ink. The 200 mg capsule shell contains FD&C blue #2, titanium dioxide, gelatin, and white ink. Thalomid (Thalidomide) Indications And Usage Multiple Myeloma Thalomid (Thalidomide) in combination with dexamethasone is indicated for the treatment of patients with newly diagnosed multiple myeloma. The effectiveness of Thalomid (Thalidomide) is based on response rates (See section.) There are no controlled trials demonstrating a clinical benefit, such as an improvement in survival. Erythema Nodosum Leprosum Thalomid (Thalidomide) is indicated for the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). Thalomid (Thalidomide) is not indicated as monotherapy for such ENL treatment in the presence of moderate to severe neuritis. Thalomid (Thalidomide) is also indicated as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence. Thalomid (Thalidomide) Warnings (see Boxed Warnings) Thalidomide is known to cause nerve damage that may be permanent. Peripheral neuropathy is a common, potentially severe, side effect of treatment with thalidomide that may be irreversible. Peripheral neuropathy generally occurs following chronic use over a period of months; however, reports following relatively short-term use also exist. The correlation with cumulative dose is unclear. Symptoms may occur some time after thalidomide treatment has been stopped and may resolve slowly or not at all. Few reports of neuropathy have arisen in the treatment of ENL despite long-term thalidomide treatment. However, the inability clinically to differentiate thalidomide neuropathy from the neuropathy often seen in Hansen’s disease makes it difficult to determine accurately the incidence of thalidomide-related neuropathy in ENL patients treated with thalidomide. Patients should be examined at monthly intervals for the first 3 months of thalidomide therapy to enable the clinician to detect early signs of neuropathy, which include numbness, tingling or pain in the hands and feet. Patients should be evaluated periodically thereafter during treatment. Patients should be regularly counseled, questioned, and evaluated for signs or symptoms of peripheral neuropathy. Consideration should be given to electrophysiological testing, consisting of measurement of sensory nerve action potential (SNAP) amplitudes at baseline and thereafter every 6 months in an effort to detect asymptomatic neuropathy. If symptoms of drug-induced neuropathy develop, thalidomide should be discontinued immediately to limit further damage, if clinically appropriate. Usually, treatment with thalidomide should only be reinitiated if the neuropathy returns to baseline status. Medications known to be associated with neuropathy should be used with caution in patients receiving thalidomide. Thalomid (Thalidomide) Precautions The only type of thalidomide exposure known to result in drug associated birth defects are as a result of direct oral ingestion of thalidomide. Currently no specific data are available regarding the cutaneous absorption or inhalation of thalidomide in women of childbearing potential and whether these exposures may result in any birth defects. Patients should be instructed to not extensively handle or open Thalomid (Thalidomide) Capsules and to maintain storage of capsules in blister packs until ingestion. If there is contact with non-intact thalidomide capsules or the powder contents, the exposed area should be washed with soap and water. Thalidomide has been shown to be present in the serum and semen of patients receiving thalidomide. If healthcare providers or other care givers are exposed to body fluids from patients receiving Thalomid (Thalidomide) (thalidomide), appropriate precautions should be utilized, such as wearing gloves to prevent the potential cutaneous exposure to Thalomid (Thalidomide) (thalidomide) or the exposed area should be washed with soap and water. Patients should be instructed about the potential teratogenicity of thalidomide and the precautions that must be taken to preclude fetal exposure as per the program and boxed warnings in this package insert. Patients should be instructed to take thalidomide only as prescribed in compliance with all of the provisions of the Restricted Distribution Program. Patients should be instructed to not extensively handle or open Thalomid (Thalidomide) (thalidomide) Capsules and to maintain storage of capsules in blister packs until ingestion. Patients should be instructed not to share medication with anyone else. Patients should be instructed that thalidomide frequently causes drowsiness and somnolence. Patients should be instructed to avoid situations where drowsiness may be a problem and not to take other medications that may cause drowsiness without adequate medical advice. Patients should be advised as to the possible impairment of mental and/or physical abilities required for the performance of hazardous tasks, such as driving a car or operating other complex machinery. Patients should be instructed that thalidomide may potentiate the somnolence caused by alcohol. Patients should be instructed that thalidomide can cause peripheral neuropathies that may be initially signaled by numbness, tingling, or pain or a burning sensation in the feet or hands. Patients should be instructed to report such occurrences to their prescriber immediately. Patients should also be instructed that thalidomide may cause dizziness and orthostatic hypotension and that, therefore, they should sit upright for a few minutes prior to standing up from a recumbent position. Patients should be instructed that they are not permitted to donate blood while taking thalidomide. In addition, male patients should be instructed that they are not permitted to donate sperm while taking thalidomide. Patients should be educated about the signs and symptoms of thromboembolism and instructed to seek medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. Two-year carcinogenicity studies were conducted in male and female rats and mice. No compound-related tumorigenic effects were observed at the highest dose levels of 3,000 mg/kg/day to male and female mice (38-fold greater than the highest recommended daily human dose of 400 mg based upon body surface area [BSA]), 3,000 mg/kg/day to female rats (75-fold the maximum human dose based upon BSA), and 300 mg/kg/day to male rats (7.5-fold the maximum human dose based upon BSA). Thalidomide was neither mutagenic nor genotoxic in the following assays: the Ames bacterial reverse mutation assay, a Chinese hamster ovary cell (AS52/XPRT) forward mutation assay, and an in vivo mouse micronucleus test. Fertility studies were conducted in male and female rabbits; no compound-related effects in mating and fertility indices were observed at any oral thalidomide dose level including the highest of 100 mg/kg/day to female rabbits and 500 mg/kg/day to male rabbits (approximately 5- and 25-fold the maximum human dose, respectively, based upon BSA). Testicular pathological and histopathological effects (classified as slight) were seen in male rabbits at dose levels ≥ 30 mg/kg/day (approximately 1.5-fold the maximum human dose based upon BSA). Thalomid (Thalidomide) Adverse Reactions The most serious toxicity associated with thalidomide is its documented human teratogenicity. (See  and ) The risk of severe birth defects, primarily phocomelia or death to the fetus, is extremely high during the critical period of pregnancy. The critical period is estimated, depending on the source of information, to range from 35 to 50 days after the last menstrual period. The risk of other potentially severe birth defects outside this critical period is unknown, but may be significant. Based on present knowledge, thalidomide must not be used at any time during pregnancy. Because thalidomide is present in the semen of patients receiving the drug, males receiving thalidomide must always use a latex condom during any sexual contact with women of childbearing potential. Thalidomide is associated with drowsiness/somnolence, peripheral neuropathy, dizziness/orthostatic hypotension, neutropenia, and HIV viral load increase. (See ) Hypersensitivity to Thalomid (Thalidomide) and bradycardia in patients treated with thalidomide have been reported. (See ) Somnolence, dizziness, and rash are the most commonly observed adverse events associated with the use of thalidomide. Thalidomide has been studied in controlled and uncontrolled clinical trials in patients with multiple myeloma and ENL and in people who are HIV-seropositive. In addition, thalidomide has been administered investigationally for more than 20 years in numerous indications. Adverse event profiles from these uses are summarized in the sections that follow. Thalomid (Thalidomide) Drug Abuse And Dependence Physical and psychological dependence has not been reported in patients taking thalidomide. However, as with other tranquilizers/hypnotics, thalidomide too has been reported to create in patients habituation to its soporific effects. Thalomid (Thalidomide) Overdosage There have been three cases of overdose reported, all attempted suicides. There have been no reported fatalities in doses of up to 14.4 grams, and all patients recovered without reported sequelae. Thalomid (Thalidomide) Storage And Dispensing This drug must not be repackaged. Store at 25º C (77º F); excursions permitted to 15-30º C (59-86º F). [See USP Controlled Room Temperature]. Protect from light. Rx only and only able to be prescribed and dispensed under the terms of the Restricted Distribution Program Manufactured for Celgene Corporation