Egrifta获美国食品药品管理局（FDA）批准治疗艾滋病患者脂肪代谢障碍 Egrifta(tesamorelin)是一种生长激素释放因子(GRF)合成类似物，为在有脂肪代谢障碍HIV患者中治疗腹部脂肪过多。 2010年11月10日EMD Serono, Inc.，德国Darmstadt，Merck KGaA的分支公司宣布美国食品和药品监督管理局已批准Egrifta (tesamorelin注射用)作为第一个和唯一治疗适用于有脂肪代谢障碍在HIV-感染患者中减少过多腹部脂肪在(腹部脂肪代谢障碍)。 伴随Egrifta (tesamorelin注射用)有使用的限制。因为未曾研究Egrifta(tesamorelin注射用)治疗的长期心血管安全性和潜在地长期心血管获益而且也不知道，在用腰围(WC)或CT扫描测量内脏脂肪组织(VAT)减低程度判断没有显示明确疗效反应的患者应小心考虑是否继续给予Egrifta(tesamorelin注射用)治疗。Egrifta (tesamorelin注射用)不适用于体重减轻处理(体重中性效应)。在HIV-阳性患者用Egrifta (tesamorelin注射用)中没有资料支持改善用抗病毒治疗依从性。 在两项3期多中心，随机化，双盲，安慰剂-对照临床试验中评价Egrifta(tesamorelin注射用)的疗效和安全性，证实在HIV-感染伴随脂肪代谢障碍遭受过量腹部脂肪患者中指机体脂肪分布和代谢异常相比安慰剂内脏脂肪组织和腰围统计显著减低。 加州大学旧金山分校，内科教授Morris Schambelan说：“当HIV-感染患者活得较长时，伴随HIV可能发生大量代谢合并症，例如腹部脂肪代谢障碍，”“随着Egrifta的批准医生现在能够为选定患者提供治疗选择以减低内脏脂肪组织。” FDA已提出三项上市后要求：一项对tesamorelin醋酸盐(Egrifta)长期观察性安全性研究，一个单次小瓶制剂–开发一种新制剂，和临床评价Egrifta(tesamorelin注射用)对糖尿病HIV-感染有脂肪代谢障碍和过量腹部脂肪患者中，对糖尿病视网膜炎是否有影响。 美国FDA批准Egrifta(tesamorelin)注射剂 批准日期：2010年11月10日；公司：Theratechnologies，一个加拿大生物药业公司，在美国由EMD Serono独家上市。. 一般描述 EGRIFTA含tesamorelin(为醋酸盐)。一类人生长激素生长因子(GRF)类似物。Tesamorelin醋酸盐的多肽前体是合成生产和由人GRF的44个氨基酸序列组成。Tesamorelin醋酸盐通过附着一个己烯酰部分制成，在3位上有一双键的一个C6链，至分子N端部分的酪氨酸残基上。Tesamorelin醋酸盐的分子式为C221H366N72O67S ? × C2H4O2 (x ≈ 7)和分子量(游离碱)是5135.9道尔顿。 Tesamorelin醋酸盐的结构式为：   EGRIFTA是一种无菌，白至淡白色，无防腐剂冻干粉为皮下注射。在用提供稀释液(注射液无菌水，USP)配制后，EGRIFTA溶液是澄明和无色。每个单次用EGRIFTA小瓶含1mg的tesamorelin为游离碱(1.1 mg tesamorelin醋酸盐，无水)和以下无活性成分：50 mg甘露醇，USP。 作用机制 在体外，tesamorelin与如内源性GRF相似效力结合和刺激人GRF受体[见临床药理学]。 生长激素生长因子(GRF)，也称为生长激素-释放激素(GHRH)，是一种下视丘多肽that作用于垂体生长激素细胞刺激内源性生长激素(GH)合成和脉冲释放，它兼有合成代谢和分解脂肪作用，GH通过相互作用与各种靶细胞上特异性受体发挥其作用，包括软骨细胞，成骨细胞，肌细胞，肝细胞，和脂肪细胞，导致一种宿主的药效动力学作用。有些，但不是全部这些效应，是主要通过肝和周边组织产生的IGF-I介导的。 适应证和用途 EGRIFTA?是一种生长激素释放因子(GRF)类似物适用于在有脂肪代谢障碍HIV-感染患者中减低过量腹部脂肪。 使用的限制(1)： 1）未曾研究EGRIFTA长期心血管效益和安全性。 2）不适用于体重减轻处理(体重中性效应)。 3）在HIV-阳性患者用EGRIFTA中没有资料支持改善用抗病毒治疗依从性。 剂量和给药方法 （1）EGRIFTA?的推荐剂量是2mg皮下注射每天1次。 剂型和规格 （1）每小瓶EGRIFTA含1mg的tesamorelin. 另一小瓶含配制用稀释液, 注射以无菌水。 禁忌证 （1）由于垂体切除术, 垂体机能减退或垂体瘤/手术, 头部放射治疗或头部创伤下丘脑-垂体轴破坏。 （2）活动性恶性病 （3）已知对tesamorelin和/或甘露醇超敏性。 （4）妊娠 警告和注意事项 （1）肿瘤：已存在恶性病应是不活动的和开始EGRIFTA治疗前其治疗完成。 （2）IGF-I升高：在所有患者中定期监视。在有持续升高患者中考虑停止。 （3）液体潴留：可能包括水肿，关节痛，和腕管综合征。 （4）葡萄糖不能耐受：随EGRIFTA使用可能发生。用EGRIFTA治疗前和期间评价葡萄糖状态。 （5）超敏性反应(如，皮疹，荨麻疹)：如怀疑建议患者立即求医。 （6）注射部位反应：建议患者旋转注射部位。 （7）急性危重病：考虑停药。 不良反应 最常报道不良反应(>5%和比安慰剂更频)：关节痛，注射部位红斑，注射部位瘙痒，肢体疼痛，外周水肿，和肌肉痛。 药物相互作用 （1）细胞色素P450-代谢药物：如与EGRIFTA?使用仔细监视。 特殊人群中使用 （1）哺乳母亲：HIV-l感染母亲不应人乳喂养以避免潜在新生后传播HIV-1。 （2）儿童使用：未确定安全性和疗效。 Contraindications •Disruption of the hypothalamic-pituitary axis due to hypophysectomy, hypopituitarism or pituitary tumor/surgery, head irradiation or head trauma •Active malignancy (either newly diagnosed or recurrent). Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with EGRIFTA® •Known hypersensitivity to tesamorelin and/or mannitol •Women who are pregnant; if pregnancy occurs, discontinue EGRIFTA® therapy Warnings and Precautions •Neoplasms: For patients with a history of non-malignant neoplasms, EGRIFTA® therapy should be initiated after careful evaluation of the potential benefit of treatment. For patients with a history of treated and stable malignancies, EGRIFTA® therapy should be initiated only after careful evaluation of the potential benefit of treatment relative to the risk of re-activation of the underlying malignancy. In addition, the decision to start treatment with EGRIFTA® should be considered carefully based on the increased background risk of malignancies in HIV-positive patients •Elevated IGF-1: EGRIFTA® stimulates GH production and increases serum IGF-1. Given that IGF-1 is a growth factor and the effect of prolonged elevations in IGF-1 levels on the development or progression of malignancies is unknown, IGF-1 levels should be monitored closely during EGRIFTA® therapy. Careful consideration should be given to discontinuing EGRIFTA® in patients with persistent elevations of IGF-1 levels (eg, >3 SDS), particularly if the efficacy response is not robust (eg, based on visceral adipose tissue changes measured by waist circumference or CT scan). During the clinical trials, patients were monitored every three months. Among patients who received EGRIFTA® for 26 weeks, 47.4% had IGF-1 levels greater than 2 standard deviation scores (SDS), and 35.6% had SDS >3, with this effect seen as early as 13 weeks of treatment. Among those patients who remained on EGRIFTA® for a total of 52 weeks, at the end of treatment 33.7% had IGF-1 SDS >2 and 22.6% had IGF-1 SDS >3 •Fluid Retention: Fluid retention may occur during EGRIFTA® therapy and is thought to be related to the induction of GH secretion. It manifests as increased tissue turgor and musculoskeletal discomfort resulting in a variety of adverse reactions (eg, edema, arthralgia, carpal tunnel syndrome) which are either transient or resolve with discontinuation of treatment •Glucose Intolerance: EGRIFTA® treatment may result in glucose intolerance. Patients treated with EGRIFTA® are at an increased risk of developing diabetes (HbA1c ≥ 6.5%). In clinical trials at week 26, a greater percentage of patients had elevated HbA1c (≥6.5%) in the EGRIFTA® group than in the placebo group (4.5% vs 1.3%). Glucose status should be carefully evaluated prior to initiating EGRIFTA® treatment and monitored periodically for changes in glucose metabolism to diagnose those who develop impaired glucose tolerance or diabetes. Caution should be exercised in treating patients with EGRIFTA® if they develop these conditions and discontinuation of treatment should be considered in patients who do not show a clear efficacy response as judged by the degree of reduction in visceral adipose tissue by waist circumference or CT scan measurements. Since EGRIFTA® increases IGF-1, patients with diabetes who are receiving ongoing treatment with EGRIFTA® should be monitored at regular intervals for potential development or worsening of retinopathy •Hypersensitivity Reactions: Hypersensitivity reactions may occur in patients treated with EGRIFTA®. Hypersensitivity reactions occurred in 3.6% of patients with HIV-associated lipodystrophy treated with EGRIFTA® in the Phase 3 clinical trials. These reactions included pruritis, erythema, flushing, urticaria, and other rash. In cases of suspected hypersensitivity reactions, patients should be advised to seek prompt medical attention and treatment with EGRIFTA® should be discontinued immediately •Injection Site Reactions: EGRIFTA® treatment may cause injection site reactions, including injection site erythema, pruritus, pain, irritation, and bruising. The incidence of injection site reactions was 24.5% in EGRIFTA®-treated patients and 14.4% in placebo-treated patients during the first 26 weeks of treatment in the Phase III clinical trials. For patients who continued EGRIFTA® for an additional 26 weeks, the incidence of injection site reactions was 6.1%. In order to reduce the incidence of injection site reactions, it is recommended to rotate the site of injection to different areas of the abdomen •Acute Critical Illness: Increased mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure has been reported after treatment with pharmacologic amounts of growth hormone. EGRIFTA® has not been studied in patients with acute critical illness. Since EGRIFTA® stimulates growth hormone production, careful consideration should be given to discontinuing EGRIFTA® in critically ill patients Drug Interactions •Cytochrome P450-Metabolized Drugs: Co-administration of EGRIFTA® with simvastatin, a sensitive CYP3A substrate, showed that EGRIFTA® had no significant impact on the pharmacokinetic profiles of simvastatin in healthy subjects. Because tesamorelin stimulates GH production, careful monitoring is advisable when EGRIFTA® is administered in combination with other drugs known to be metabolized by CYP450 liver enzymes Immunogenicity •Antibody formation may occur with the use of therapeutic peptide products. Anti-tesamorelin IgG antibodies were detected in approximately half of patients treated with EGRIFTA® and generally disappeared over time after discontinuation of treatment. Antibodies did not appear to impact the efficacy of EGRIFTA® Use in Specific Populations •Nursing Mothers: Because of both the potential for HIV-1 infection transmission and serious adverse reactions in nursing infants, mothers receiving EGRIFTA® should be instructed not to human milk-feed •Pediatric Use: Safety and effectiveness in pediatric patients have not been established. EGRIFTA® should not be used in children with open epiphyses, among whom excess GH and IGF-1 may result in linear growth acceleration and excessive growth •Geriatric Use: There is no information on the use of EGRIFTA® in patients greater than 65 years of age with HIV and lipodystrophy •Renal and Hepatic Impairment: Safety, efficacy, and pharmacokinetics of EGRIFTA® in patients with renal or hepatic impairment have not been established 附件： 2011112021090122.PDF     --------------------------------------------------------------- 产地国家: 美国 原产地英文商品名: EGRIFTA 1mg/vial 60vials/box 原产地英文药品名: TESAMORELIN ACETATE 中文参考商品译名: EGRIFTA 1毫克/瓶 60瓶/盒 中文参考药品译名: 醋酸替莫瑞林 生产厂家中文参考译名: THERATECHNOLOGIES 生产厂家英文名: THERATECHNOLOGIES