Cerdelga（eliglustat）硬明胶胶囊获FDA已批准用作特定1型戈谢病（Gaucher disease）成人患者唯一的一线口服疗法。Cerdelga不适用于经基因检测证实对Cerdelga代谢更快或代谢速度不确定的少数患者 FDA的药物评价和研究中心药物评价III室副主任Amy G. Egan，M.D.，M.P.H.说：“今天的批准为1型戈谢病病人提供另外重要治疗选择，”“此外，Cerdelga接受FDA的孤儿药物指定，反映监管局专注和承诺治疗的发展罕见疾病。”。优先审评。 批准日期：2014年8月19日；公司：Genzyme Corporation CERDELGA™（细菌素 eliglustat）胶囊，用于口服使用 美国初步批准：2014年 作用机制 戈谢病是由溶酶体酶酸β-葡萄糖苷酶的缺乏引起的。酸性β-葡糖苷酶催化鞘脂葡糖脑苷脂转化为葡萄糖和神经酰胺。酶缺乏导致葡萄糖神经酰胺（GL-1）主要在巨噬细胞的溶酶体区室中的积累，产生泡沫细胞或“Gaucher细胞”。 CERDELGA是葡萄糖神经酰胺合酶的特异性抑制剂（IC50 = 10 ng / mL），作为GD1的底物减少疗法。在临床试验中，CERDELGA减少脾脏和肝脏大小，改善贫血和血小板减少症。 在这种溶酶体贮积症（LSD）中，临床特征反映了Gaucher细胞在肝，脾，骨髓和其他器官中的积累。高斯细胞在肝，脾和骨髓中的积累导致器官大和骨骼疾病。在骨髓和脾中存在戈谢细胞导致临床上显着的贫血和血小板减少。 适应症和用法 CERDELGA是一种葡萄糖神经酰胺合酶抑制剂，用于长期治疗1型戈谢病的成人患者，这些患者是通过FDA批准的试验检测的CYP2D6广泛代谢物（EMs），中间代谢物（IMs）或低代谢物（PMs） 。 使用限制： CYP2D6超快速代谢剂可能无法达到足够的CERDELGA浓度以达到治疗效果 不推荐用于CYP2D6不确定代谢者的特定剂量 剂量和给药 使用FDA批准的测试选择患者来确定CYP2D6基因型 CYP2D6 EM或IM：84mg口服每天两次 CYP2D6 PMs：84mg每日一次口服 吞咽胶囊整体，不粉碎，溶解或打开胶囊 避免吃葡萄柚或喝葡萄柚汁 剂量形式和强度 84 mg胶囊 禁忌症 CYP2D6 EMs和IMs采取强或中等的CYP2D6抑制剂与强或中度CYP3A抑制剂 采用强CYP3A抑制剂的CYP2D6IMs和PMs 警告和注意事项 心脏心律失常的心电图变化和潜力：不建议在既有心脏病，长QT综合征和伴随使用IA类和III类抗心律失常药的患者中 不良反应 最常见的不良反应（≥10％）是：疲劳，头痛，恶心，腹泻，背痛，四肢疼痛和上腹痛 药物相互作用 Eliglustat是CYP2D6和CYP3A底物。 CERDELGA与抑制CYP2D6和CYP3A的药物的共同给药可以显着增加对细菌素暴露的暴露并导致PR，QTc和/或QRS心脏间隔的延长，这可能导致心律失常。考虑在治疗之前和期间潜在的药物相互作用 CYP2D6 IMs和PMs服用中度CYP3A抑制剂：不推荐 CYP2D6 PMs服用弱CYP3A抑制剂：不推荐 采用强或中度CYP2D6抑制剂的CYP2D6 EM和IM和采取强或中等CYP3A抑制剂的CYP2D6 EM：将剂量减少至每日一次84mg Eliglustat是P-gp和CYP2D6的抑制剂。与作为P-gp或CYP2D6底物的药物的共同给药可能导致其他药物的浓度增加 有关临床显着药物相互作用的列表，请参阅完整处方信息 在特定人群中使用 怀孕：只有当潜在利益证明潜在风险时才施行。根据动物数据，可能导致胎儿损伤 护理母亲：根据药物对母亲的重要性停止使用药物或护理 肾损伤：不建议在中重度损伤 肝功能损害：不推荐 供应/存储和处理 CERDELGA以84mg硬明胶胶囊提供，具有珍珠蓝绿色不透明盖和在黑色中印有“GZ02”的珍珠白色不透明体。 CERDELGA 84 mg胶囊如下： NDC-58468-0220-1  - 包含4个胶囊（共56个胶囊）的纸箱。 每个包由14个胶囊的1张吸塑卡和一个纸板钱包组成。 NDC-58468-0220-2  - 包含1包胶囊（共14个胶囊）的纸箱。 每个包由14个胶囊的一个吸塑卡和一个纸板钱包。 储存在68°F  -  77°F（20°C  -  25°C），允许在59°F和86°F（15°C到30°C）之间的偏差[参见USP控制室温]。 国外上市：2014年9月获FDA批准上市，2015年1月获欧盟批准上市，2015年3月在日本上市。 国内报批：2010年健赞（Genzyme）公司提交本品的进口申请，2011年7月已批准临床。国内企业尚无申报。 CERDELGA(ELIGLUSTAT TARTRATE) CAPSULE ORAL CERDELGA is a glucosylceramide synthase inhibitor indicated for the long-term treatment of adult patients with Gaucher disease type 1 who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) as detected by an FDA-cleared test. CYP2D6 ultra-rapid metabolizers may not achieve adequate concentrations of CERDELGA to achieve a therapeutic effect. A specific dose cannot be recommended for CYP2D6 indeterminate metabolizers. CERDELGA™ (eliglustat) capsules, for oral use。 CERDELGA Rx Pharmacological Class: Glucosylceramide synthase inhibitor. Active Ingredient(s): Eliglustat 84mg; hard-gelatin caps. Company Genzyme Corporation Indication(s): Long-term treatment of adults with Gaucher disease type 1 who are CYP2D6 extensive, intermediate, or poor metabolizers as detected by an FDA-cleared test. Limitations of use: CYP2D6 ultra-rapid metabolizers may not achieve adequate concentrations for a therapeutic effect. No dosage recommendation for CYP2D6 indeterminate metabolizers. Pharmacology: Cerdelga is a specific inhibitor of glucosylceramide synthase and acts as a substrate reduction therapy for Gaucher disease type 1. In clinical trials, Cerdelga reduced spleen and liver size, and improved anemia and thrombocytopenia. Clinical Trials: The efficacy of Cerdelga was evaluated in 3 clinical trials in patients with Gaucher disease type 1. Trial 1 was a randomized, double-blind, placebo-controlled, multi-center study evaluating the efficacy and safety of Cerdelga in 40 treatment-naïve patients ≥16 years old with pre-existing splenomegaly and hematological abnormalities. The Cerdelga treatment group consisted of intermediate (5%), extensive (90%), and ultra-rapid (5%) metabolizers. Patients randomized to Cerdelga received an initial dose of 42mg twice daily, with an increase up to 84mg twice daily possible at Week 4 based on the plasma trough concentration at Week 2. The primary endpoint was the percentage change in spleen volume from baseline to 9 months as compared to placebo. Secondary endpoints were absolute change in hemoglobin level, percentage change in liver volume, and percentage change in platelet count from baseline to 9 months compared to placebo. During the 9-month primary analysis period, Cerdelga demonstrated statistically significant improvements in all primary and secondary endpoints compared to placebo. Results in the Cerdelga treatment group showed a –27.8% change in spleen volume vs. 2.3% in the placebo group (treatment difference –30.0, [95% CI: –36.8, –23.2]; P<0.0001). Furthermore, the percentage change in platelet count was 32.0% in the Cerdelga group vs. –9.1% in the placebo group (treatment difference 41.1, [95% CI: 24.0, 58.2]; P<0.0001). In an uncontrolled study of treatment-naïve Gaucher disease type 1 patients, improvements in spleen and liver volume, hemoglobin level, and platelet count continued through the 4-year treatment period. For more clinical trials data, see full labeling. Legal Classification: Rx Adults: Swallow whole with water. Extensive and intermediate metabolizers: 84mg twice daily. Poor metabolizers: 84mg once daily; monitor. Extensive and intermediate metabolizers taking strong or moderate CYP2D6 inhibitors (eg, paroxetine, terbinafine); or extensive metabolizers taking strong or moderate CYP3A inhibitors (eg, ketoconazole, fluconazole): reduce to 84mg once daily. Currently on imiglucerase, velaglucerase alfa, or taligucerase alfa: administer eliglustat 24hrs after last dose of the previous enzyme replacement therapy. Children: Not established. Contraindication(s): Extensive or intermediate metabolizers taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor. Intermediate or poor metabolizers taking a strong CYP3A inhibitor (eg, ketoconazole). Warnings/Precautions: Determine CYP2D6 genotype using an FDA-cleared test. Pre-existing cardiac disease (CHF, recent MI, bradycardia, heart block, ventricular arrhythmia), long QT syndrome: not recommended. Moderate-to-severe renal impairment, ESRD, hepatic impairment, cirrhosis: not recommended. Pregnancy (Cat.C). Nursing mothers: not recommended. Interaction(s) See Contraindications. Increased risk of arrhythmias with concomitant CYP2D6 and CYP3A inhibitors; adjust dose based on metabolizer status (see full labeling). Avoid grapefruit or grapefruit juice. Concomitant Class IA (eg, quinidine, procainamide) and Class III (eg, amiodarone, sotalol) antiarrhythmics, CYP3A inducers (eg, rifampin, carbamazepine, phenobarbital, phenytoin, St. John’s wort): not recommended. Concomitant digoxin; reduce digoxin dose by 30% and monitor. Potentiates P-gp substrates (eg, phenytoin, colchicine, dabigatran etexilate) or CYP2D6 substrates (eg, metoprolol, tricyclic antidepressants, phenothiazines); monitor and consider reducing dose of these drugs. Adverse Reaction(s) Fatigue, headache, nausea, diarrhea, back pain, pain in extremities, upper abdominal pain; ECG changes, arrhythmias. How Supplied: Blister card (14 caps)—1, 4 LAST UPDATED: 10/31/2014 Cerdelga (Eiglustat Capsules) Indication & Usage CERDELGA (eliglustat) capsules is a glucosylceramide synthase inhibitor indicated for the long-term treatment of adult patients with Gaucher disease type 1 who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) as detected by an FDA-cleared test. CYP2D6 ultra-rapid metabolizers may not achieve adequate concentrations of CERDELGA to achieve a therapeutic effect. A specific dose cannot be recommended for CYP2D6 indeterminate metabolizers. Important Safety Information CERDELGA (eliglustat) capsules are a prescription medicine used for the long-term treatment of Gaucher disease type 1 (GD1) in certain adults. Your doctor will perform a test to help determine if CERDELGA is right for you. It is not known if CERDELGA is safe and effective in children. Before taking CERDELGA, tell your doctor about all of your medical conditions, including kidney or liver problems, history of heart attacks, or heart rhythm problems (including long QT syndrome). If you are pregnant or plan to become pregnant or breastfeed, talk to your physician. It is not known if CERDELGA will harm your unborn baby. CERDELGA can affect the way other medicines work and other medicines can affect how CERDELGA works. Using CERDELGA with other medicines or herbal supplements (including St. John’s Wort) may cause an increased risk of side effects, including ECG changes and irregular heart beat. Especially tell your doctor if you take medicines for fungal infections, tuberculosis, seizures, heart rhythm and rate problems, high blood pressure, or depression or other mental health problems. Your doctor may need to prescribe a different medicine, change your dose of other medicines, or change your dose of CERDELGA. Tell your doctor about any new medicines before you start taking them. Swallow the capsule whole. If you miss a dose of CERDELGA, take the next dose at the usual time. Do not take two doses of CERDELGA at the same time. Avoid eating or drinking grapefruit products while taking CERDELGA. Grapefruit products can increase the amount of CERDELGA in your body. The most common adverse reactions (≥10%) for CERDELGA are: fatigue, headache, nausea, diarrhea, back pain, pain in extremities, and upper abdominal pain. Call your doctor for medical advice about adverse effects. You may report adverse effects to FDA at 1-800-FDA-1088. If you would like more information, talk with your doctor. You may also go to www.cerdelga.com for the。