新类型降脂药物PRALUENT(ALIROCUMAB)INJECTABLE;INJECTION获美国FDA批准为新一代降脂药PCSK9抑制剂 近日，美国FDA批准Praluent（alirocumab）注射液，这是在美国获批的首个前蛋白转化酶枯草溶菌素9（PCSK9）抑制剂类降胆固醇治疗药物。 Praluent被批准用于除了节食及最大限度耐受他汀药物治疗的患有杂合子家族性高胆固醇血症（HeFH）成年患者，或临床上有动脉纱粥样硬化心血管疾病如心脏病发作或中风的患者，这些患者需要额外地降低 LDL胆固醇水平。 HeFH是一种遗传性疾病，其能导致高水平的低密度脂蛋白（LDL）胆固醇。血液中高水平的LDL胆固醇（称「坏」胆固醇）与心血管疾病相关。心脏病是美国男女患者死亡的第一大因素。据美国疾病控制与预防中心提供的信息，美国每年大约有61万人死于心脏疾病，这相当于每四例死亡中就有一例死于心脏病。 可注射降胆固醇药物的新类别中第一个。药物评价和研究中心新药办公室主任说：“对有HeFH或有已知的心血管病患者用他汀类药物未能足够降低他们的LDL胆固醇Praluent提供另外治疗选择，” “FDA强力支持继续工作以提供新和创新选择为治疗和预防心血管病。 批准日期：2015年7月24日；公司：Sanofi和Regeneron 制药 PRALUENTTM(alirocumab)注射液，为皮下使用 美国初次批准：2015 作用机制 Alirocumab是一种人单克隆抗体结合至前蛋白转化酶枯草溶菌素9型(PCSK9)。PCSK9结合至在肝细胞表面的低密度脂蛋白受体(LDLR)促进LDLR在肝内降解。LDLR是清除循环的LDL的主要受体，因此通过PCSK9导致LDL-C较高血水平LDLR水平减低。通过抑制前蛋白转化酶枯草溶菌素9[PCSK9]的结合至LDLR，alirocumab增加可得到的清除LDL的LDLRs数，从而降低LDL-C水平。 适应证和用途 PRALUENT是一种PCSK9(前蛋白转化酶枯草溶菌素9型)抑制剂抗体适用作为对膳食和最大耐受他汀类治疗辅助为治疗有杂合子家族性高胆固醇血症或临床动脉粥样硬化心血管病，需要LDL-胆固醇(LDL-C)另外降低的成年 尚未确定PRALUENT对心血管发病率和死亡率的影响。 剂量和给药方法 对PRALUENT推荐起始剂量是75 mg皮下给予每2周1次，自从患者的大多数用这个剂量实现足够的LDL-C降低。如LDL-C反应不佳，剂量可增加至最大剂量150 mg给予每2周。 开始的4至8周内测量LDL-C水平或需要时滴定调整PRALUENT，评估反应和调整剂量。 剂型和规格 ⑴注射液：75mg/mL或150mg/mL溶液在一个单剂量预装笔中 ⑵注射液：75mg/mL或150mg/mL溶液在一个单剂量预装注射器中 禁忌证 对PRALUENT严重超敏性反应病史 警告和注意事项 用PRALUENT治疗曾报道过敏反应：超敏性反应(如，瘙痒，皮疹，寻麻症)，包括有些严重事件(如，超敏性血管炎和超敏性反应需要住院)。如发生严重过敏反应的体征和症状，终止用PRALUENT治疗，按照标准医护处理，和监视直至体征和症状解决。 不良反应 最常发生不良反应(≥5%的用PRALUENT治疗患者和发生更频于安慰剂)是鼻咽炎，注射部位反应，和流感。 包装规格/贮存和处置 PRALUENT是一种透明，无色至浅黄溶液，supplied在单剂量预装笔和单剂量预装玻璃注射器中供应。PRALUENT的每支预装笔或预装注射器被设计成输送1 mL的75 mg/mL或150 mg/mL 溶液。 可得到PRALUENT在纸盒中含1或2，预装笔和1或2，预装注射器。 贮藏在冰箱在36°F至46°F(2°C至8°C)为了避光保护在外纸盒中。 不要冻结。不要暴露于极热。不要摇动。 PRALUENT(alirocumab) Injection PRALUENT Rx Pharmacological Class: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor. Active Ingredient(s): Alirocumab 75mg/mL, 150mg/mL; per prefilled pen or syringe; soln for SC inj; preservative-free. Company Sanofi and Regeneron Indication(s): Adjunct to diet and maximally tolerated statin therapy, in adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic ­cardiovascular disease requiring additional lowering of LDL-C. Limitations of use: effect on cardiovascular morbidity and mortality has not been determined. Pharmacology: Alirocumab is a human monoclonal antibody that binds to PCSK9. PCSK9 binds to the low-density lipoprotein receptors (LDLR) on the surface of hepatocytes to promote LDLR degradation within the liver. By inhibiting the binding of PCSK9 to LDLR, alirocumab increases the number of LDLRs available to clear LDL, thereby lowering LDL-C levels. Clinical Trials: The efficacy of Praluent was studied in 5 double-blind, placebo-controlled trials that enrolled 3,499 patients; 3 of the 5 trials were exclusively studied in patients with heterozygous familial hypercholesterolemia. All patients were receiving a maximally tolerated dose of a statin, with or without other lipid-modifying therapies. Three studies used an initial dose of 75mg every 2 weeks followed by criteria-based up-titration to 150mg every 2 weeks at Week 12 for those who did not meet their pre-defined target LDL-C at Week 8; two studies only used a dose of 150mg every 2 weeks. Study 1 randomized 1,553 patients to Praluent 150mg every 2 weeks and 788 patients to placebo. At Week 24, the treatment difference between Praluent and placebo in mean LDL-C percent change was −58% (95% CI: −61%, −56%; P<0.0001). Study 2 randomized 209 patients to Praluent and 107 to placebo. At Week 24, the mean percent change from baseline in LDL-C was −44% with Praluent and −2% with placebo. The treatment difference between Praluent and placebo in mean LDL-C percent change was −43% (95% CI: −50%, −35%; P<0.0001). The dose was up-titrated to 150mg every 2 weeks in 32 patients treated with Praluent for at least 12 weeks. Studies 3 and 4 randomized a total of 490 patients to Praluent and 245 to placebo. At Week 12, the treatment difference between Praluent 75mg every 2 weeks and placebo in mean LDL-C percent change was −48% (95% CI: −52%, −44%). At Week 24, the mean treatment difference between Praluent and placebo in mean LDL-C percent change from baseline was −54% (95% CI: −59%, −50%; P<0.0001). The dose was up-titrated to 150mg every 2 weeks in 196 patients treated with Praluent for at least 12 weeks. The LDL-C lowering effect was sustained to Week 52. Study 5 randomized 72 patients to Praluent 150mg every 2 weeks and 35 patients to placebo. At Week 24, the mean percent change from baseline in LDL-C was −43% with Praluent and −7% with placebo. The treatment difference between Praluent and placebo in mean LDL-C percent change was −36% (95% CI: −49%, −24%; P<0.0001). For more clinical trial data, see full labeling. Legal Classification: Rx Adults: Give by SC injection into thigh, abdomen, or upper arm; rotate injection sites. Initially 75mg once every 2 weeks; if inadequate LDL-C response, may increase to max 150mg given every 2 weeks. Measure LDL-C levels within 4–8 weeks of initiation or titration; adjust dose if needed. Children: Not established. Warnings/Precautions: Do not inject into areas of active skin disease or injury (eg, sunburns, rashes, inflammation, skin infections). Discontinue if serious allergic reactions occur. Pregnancy (2nd & 3rd trimesters). Nursing mothers. Interaction(s) Avoid co-administration with other injectable drugs at same injection site. Adverse Reaction(s) Nasopharyngitis, injection site reactions (eg, erythema/redness, itching, swelling, pain/tenderness), influenza. How Supplied: Single-dose prefilled pen or syringe (1mL)—1, 2 LAST UPDATED: 8/18/2015