英文药名：SYLATRON (peginterferon alfa-2b for Injection) 中文药名：聚乙二醇干扰素α- 2b注射剂 生产厂家：先灵药业 药品介绍： 聚乙二醇干扰素α-2b（Peginterferon alfa-2b）于2011年3月29日美国FDA批准用于治疗涉及到淋巴结且已接受过外科切除术的黑色素瘤。该药由先灵药业公司（Schenng Corporation）生产，商品名称为Sylatron。在临床试验中，服用Sylatron的患者黑色素瘤复发时间比不服药者要延后大约9个月。 适应证和用途 SYLATRON是一种α干扰素适用于显微镜或大体肉眼累及淋巴结黑色素瘤与84天内最终手术切除包括完整的淋巴结清扫术的辅助治疗。 剂量和给药方法 （1）6 μg/kg/周皮下共8剂随后； （2）3 μg/kg/周皮下直至5年。 剂型和规格 （1）296 μg冻干粉每单次使用小瓶 （2）444 μg冻干粉每单次使用小瓶 （3）888 μg冻干粉每单次使用小瓶 禁忌证 （1）已知对聚乙二醇干扰素α-2b或干扰素α-2b严重超敏反应。 （2）自身免疫性肝炎。 （3）肝失代偿(Child-Pugh评分 >6 [类别B和C])。 警告和注意事项 （1）抑郁和其它严重神经精神不良反应。 （2）重要或不稳定心脏病史。 （3）视网膜疾病。 （4）Child-Pugh评分>6(类别B和C)。 （5）不能用药物有效治疗的甲状腺功能减退，甲状腺功能亢进，高血糖，糖尿病。 不良反应 最常见不良反应(>60%)是：疲乏，ALT增高，AST增高，发热，头痛，厌食，肌肉痛，恶心，畏寒，和注射部位反应。 为报告怀疑不良反应，联系Schering Corporation电话1-800-526-4099或FDA电话1-800-FDA-1088或www.fda.gov/medwatch. 药物相互作用 药物被细胞色素P-450(CYP)酶代谢：当与被CYP2C9或CYP2D6代谢药物联用时严密监视。 在特殊人群中的使用 （1）妊娠：根据动物资料，可能致胎儿危害。 （2）儿童：尚未确定<18岁患者中安全性和疗效。 （3）肾受损：有中度和严重肾受损患者中增加监查SYLATRON毒性频度。 SELECT IMPORTANT SAFETY INFORMATION WARNING: DEPRESSION AND OTHER NEUROPSYCHIATRIC DISORDERS The risk of serious depression, with suicidal ideation and completed suicides, and other serious neuropsychiatric disorders are increased with alpha interferons, including SYLATRON. Permanently discontinue SYLATRON in patients with persistently severe or worsening signs or symptoms of depression, psychosis, or encephalopathy. These disorders may not resolve after stopping SYLATRON. View additional SELECT IMPORTANT SAFETY INFORMATION for SYLATRON   In the Registration Phase 3 Study •Once-weekly dose of SYLATRON was adjusted to maintain an ECOG Performance Status of 0 or 1. •Patients achieved a significant improvement in relapse-free survival: ◦Based on 696 RFS events, determined by the Independent Review Committee. ◦Median RFS was 34.8 months (95% CI, 26.1–47.4) and 25.5 months (95% CI, 19.6–30.8) in the group treated with SYLATRON and the observation group, respectively. ◦The estimated hazard ratio for RFS was 0.82 (95% CI, 0.71–0.96; unstratified log-rank P=0.011) in favor of SYLATRON. SELECT IMPORTANT SAFETY INFORMATION SYLATRON is contraindicated in patients with a history of anaphylaxis to peginterferon alfa-2b or interferon alfa-2b, in patients with autoimmune hepatitis, and in patients with hepatic decompensation (Child-Pugh score >6 [Class B and C]). Peginterferon alfa-2b can cause life-threatening or fatal neuropsychiatric reactions. These include suicide, suicidal and homicidal ideation, depression, and an increased risk of relapse of recovering drug addicts. Depression occurred in 59% of patients treated with SYLATRON and 24% of patients in the observation group. Depression was severe or life threatening in 7% of patients treated with SYLATRON compared with <1% of patients in the observation arm. Monitor and evaluate patients for signs and symptoms of depression and other psychiatric symptoms every 3 weeks during the first 8 weeks of treatment and every 6 months thereafter. Monitor patients during treatment and for at least 6 months after the last dose of SYLATRON. Permanently discontinue SYLATRON for persistent severe or worsening psychiatric symptoms or behaviors and refer for psychiatric evaluation. Cardiac adverse reactions, including myocardial infarction, bundle-branch block, ventricular tachycardia, and supraventricular arrhythmia, occurred in 4% of patients treated with SYLATRON compared with 2% of patients in the observation group. Hypotension, cardiomyopathy, and angina pectoris have occurred in patients treated with peginterferon alfa-2b. Permanently discontinue SYLATRON for new onset of ventricular arrhythmia or cardiovascular decompensation. Peginterferon alfa-2b can cause decrease in visual acuity or blindness due to retinopathy. Retinal and ocular changes including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, papilledema, and serous retinal detachment may be induced or aggravated by treatment with peginterferon alfa-2b or other alpha interferons. The overall incidence of serious retinal disorders, visual disturbances, blurred vision, and reduction in visual acuity was <1% in both patients treated with SYLATRON and those in the observation group. Perform an eye examination that includes assessment of visual acuity and indirect ophthalmoscopy or fundus photography at baseline in patients with preexisting retinopathy and at any time during treatment with SYLATRON in patients who experience changes in vision. Permanently discontinue SYLATRON in patients who develop new or worsening retinopathy. Peginterferon alfa-2b increases the risk of hepatic decompensation and death in patients with cirrhosis. Monitor hepatic function with serum bilirubin, ALT, AST, alkaline phosphatase, and LDH at 2 and 8 weeks, and 2 and 3 months, following initiation of SYLATRON, then every 6 months while receiving SYLATRON. Permanently discontinue SYLATRON for evidence of severe (Grade 3) hepatic injury or hepatic decompensation (Child-Pugh score >6 [Class B and C]). Peginterferon alfa-2b can cause new onset or worsening of hypothyroidism, hyperthyroidism, and diabetes mellitus. Hypothyroidism developed in 1% of patients treated with SYLATRON. The overall incidence of endocrine disorders was 2% in patients treated with SYLATRON compared to <1% for patients in the observation group. Obtain TSH levels within 4 weeks prior to initiation of SYLATRON, at 3 and 6 months following initiation, then every 6 months thereafter while receiving SYLATRON. Permanently discontinue SYLATRON in patients who develop hypothyroidism, hyperthyroidism, or diabetes mellitus that cannot be effectively managed. The most common adverse reactions in patients treated with SYLATRON vs observation were fatigue (94% vs 41%), increased ALT (77% vs 26%), increased AST (77% vs 26%), pyrexia (75% vs 9%), headache (70% vs 19%), anorexia (69% vs 13%), myalgia (68% vs 23%), nausea (64% vs 11%), chills (63% vs 6%), and injection site reaction (62% vs 0%). The most common serious adverse reactions in patients treated with SYLATRON vs observation were fatigue (7% vs <1%), increased ALT (3% vs <1%), increased AST (3% vs <1%), and pyrexia (3% vs <1%). Thirty-three percent of patients receiving SYLATRON discontinued treatment due to adverse reactions. When administering SYLATRON with medications metabolized by CYP2C9 or CYP2D6, the therapeutic effect of these drugs may be altered. There are no adequate and well-controlled studies of SYLATRON in pregnant women. Use SYLATRON during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether the components of SYLATRON are excreted in human milk. Because of the potential for adverse reactions from the drug in nursing infants, a decision must be made whether to discontinue nursing or discontinue treatment with SYLATRON. Safety and effectiveness in patients below the age of 18 years have not been established. Increase frequency of monitoring for toxicity with SYLATRON in patients with moderate and severe renal impairment. Before prescribing SYLATRON, please read the Prescribing Information, including the Boxed Warning about depression and other neuropsychiatric disorders. The Medication Guide and Instructions for Use also are available. SYLATRON Rx Generic Name and Formulations: Peginterferon alfa-2b 296mcg, 444mcg, 888mcg; per vial; pwd for SC inj after reconstitution. Company: Merck & Co., Inc. Indications for SYLATRON: Adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy. Adult Dose for SYLATRON: ≥18yrs: Give by SC inj. Rotate inj sites. Premedicate with acetaminophen. 6mcg/kg/week for 8 doses, followed by 3mcg/kg/week for up to 5 years. Withhold dose if ANC <0.5x109/L, platelets <50x109/L, ECOG PS ≥2, or for non-hematologic toxicity ≥ Grade 3. Resume at reduced dose (see literature) when: ANC ≥0.5x109/L, platelets ≥50x109/L, ECOG PS 0–1, and non-hematologic toxicity has completely resolved or improved to Grade 1. Children's Dose for SYLATRON: <18yrs: not established. Pharmacological Class: Alpha interferon. Contraindications: Anaphylaxis to peginterferon alfa-2b or interferon alfa-2b. Autoimmune hepatitis. Hepatic decompensation (Child-Pugh score >6 [Class B and C]). Warnings/Precautions: Increased risk of depression and other neuropsychiatric disorders. Permanently discontinue for: persistent severe or worsening neuropsychiatric disorders (eg, depression, psychosis, encephalopathy); new onset ventricular arrhythmia or cardiovascular decompensation; new or worsening retinopathy; severe (Grade 3) hepatic injury or hepatic decompensation; hypothyroidism, hyperthyroidism, or diabetes mellitus that cannot be effectively managed; or if unable to tolerate a dose of 1mcg/kg/week. Monitor for signs/symptoms of depression/psychosis every 3 weeks during first 8 weeks, then every 6 months, continue for at least 6 months after last dose. Perform eye exam in patients with retinopathy and those with vision changes during therapy. Monitor hepatic function with serum bilirubin, ALT/AST, alkaline phosphate, and LDH at 2 and 8 weeks, and 2 and 3 months following initiation, then every 6 months. Obtain TSH levels within 4 weeks prior to initiation, at 3 and 6 months following initiation, then every 6 months. Moderate-to-severe renal impairment (monitor). Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Therapeutic effect of drugs metabolized by CYP2C9 or CYP2D6 may be altered. Adverse Reactions: Fatigue, increased ALT/AST, pyrexia, headache, anorexia, myalgia, nausea, chills, inj site reactions; neuropsychiatric disorders. Elimination: Renal. Generic Availability: NO How Supplied: Single-use vial—1, 4 (w. diluent) 美国FDA批准聚乙二醇干扰素α-2b（Sylatron）用于治疗黑色素瘤 2011年3月29日美国FDA批准聚乙二醇干扰素α-2b（Peginterferon alfa-2b） 用于治疗涉及到淋巴结且已接受过外科切除术的黑色素瘤。该药由先灵药业公司（Schering Corporation）生产，商品名称为Sylatron。在临床试验中，服用Sylatron的患者黑色素瘤复发时间比不服药者要延后大约9个月。 聚乙二醇干扰素α-2b治疗可在施行淋巴切除术或其他外科手术后的84天内开始。 该药的批准是基于一项为期5年的多中心临床试验的结果，总共有1256名黑色素瘤患者参加了这个试验，试验数据由一个独立的不知情委员会进行审核。 在试验中，黑色素瘤患者被随机分成两组，一组服用聚乙二醇干扰素α-2b，另一组（观察组）不服。在头两年，每3个月对试验对象作一次肿瘤转移情况检查，余下3年里则每6个月检查一次。试验的疗效终点是无复发生存时间（relapse-free survival,RFS），FDA对此下的定义是“（从开始用药）到最早出现局部复发、远处转移或死亡的时间”（"the time to the earliest of local or regional recurrence, distant metastases, or death."）。 在696个出现黑色素瘤复发的患者中，服用聚乙二醇干扰素α-2b者平均RFS为34.8个月，95%可信区间（confidence interval,CI）为26.1-47.4；而未服用聚乙二醇干扰素α-2b者其RFS则为25.5个月，95%可信区间为19.6-30.8。 聚乙二醇干扰素α-2b并不会影响两组实验对象的整体生存率，两组风险比（hazard ratio）为0.98；95%可信区间为0.82-1.16。5年研究期限到期后，有525名患者已经死亡。 聚乙二醇干扰素α-2b推荐用药方法是，先用6微克/公斤体重/周的剂量皮下注射8周，往后剂量减至3微克/公斤体重/周，治疗期可一直持续5年。 FDA报告说，服用聚乙二醇干扰素α-2b的患者有三分之一因为副作用而停止用药。超过60%的服药者出现以下副作用：困惓、丙氨酸氨基转移酶和天门冬氨酸氨基转移酶水平升高、发烧、头痛、食欲不振、肌痛、恶心、冷颤和注射部位反应等。 有5名服用聚乙二醇干扰素α-2b的患者在停药30内死亡，其中2人死于心血管疾病，FDA表示这两例死亡可能与聚乙二醇干扰素α-2b的使用有关联。 Sylatron是FDA在2011年批准的第二种治疗黑色素瘤药物，也是2011年批准的第三种抗肿瘤药。在3月25日，FDA批准了布迈施贵宝公司的Yervoy（ipilimumab注射液）用于治疗转移性或无法实施外科切除术的黑色素瘤。