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——Jakafi（磷酸鲁索替尼）在美获批首款治疗真性红细胞增多症
2014年12月4日，美国FDA批准鲁索替尼；商品名Jakafi)用于治疗真性红细胞增多症患者，这是一种慢性骨髓疾病。在美国鲁索替尼是获批用于这一疾病的首款药物。
当骨髓制造太多红细胞时会发生真性红细胞增多症，患者可能经历白细胞及血小板增多。血细胞过多可导致脾脏肿大、出血问题及皮肤附近静脉发生血栓（静脉炎）。此外，这种疾病使患者处于中风或心脏病发作风险增加的境地。
鲁索替尼的新适应症旨在治疗对羟基脲没有充分响应或不能耐受的真性红细胞增多症患者，羟基脲是另一款通常用来降低血液中红细胞及血小板数量的药物。鲁索替尼通过抑制参与调节血液及免疫功能的Janus相关激酶(JAK)1和2发挥作用。这款药物获批治疗真性红细胞增多症将帮助降低脾肿大的发生及静脉切开术的需求，静脉切开术是将体内过多血液移出体外的一种手术。
“鲁索替尼获批用于真性红细胞增多症凸显了开发药物以与我们日益增长的疾病机理知识相匹配的重要性，，”FDA药物评价与研究中心血液及肿瘤产品办公室主任、医学博士Pazdur称。“用来评价鲁索替尼的试验证实减少脾脏体积及静脉切开术来控制这一疾病的临床意义。”
鲁索替尼治疗真性红细胞增多症的安全性及有效性在一项由222名受试者参与的试验中得到评价，这些受试者患有该疾病至少有24周时间，他们对羟基脲已没有充分响应或不能耐受，实施过静脉切开术及显示脾肿大。受试者被随机配给鲁索替尼或最好的现有可供使用治疗药物。
这项研究旨在检测在治疗第8周及继续治疗完成32周时对静脉切开术的需求，及在第32周时脾脏体积减小35%的情况。结果显示，21%的鲁索替尼治疗受试者经历了静脉切开术需求减少及脾脏体积减小，相比之下，接受现有最好治疗的受试者只有1%的患者达到这一指标。
在真性红细胞增多症受试者中，最常见的与使用鲁索替尼相关的副作用有低红细胞计数 (贫血)及低血小板计数(血小板减少症)。最常见的非血液相关副作用有头晕、便秘和带状疱疹。
FDA对鲁索替尼用于真性红细胞增多症的审评是通过优先审评程序完成的，因为在其申请资料被提交时，这款药物证实与现有治疗药物相比，对一种严重疾病治疗的安全性及有效性有明显的改善。优先审评可为一款药物的审评提供一个加快的审评过程。鲁索替尼因旨在治疗一种罕见疾病，其还获得孤儿药资格。
2011年，FDA批准鲁索替尼用于患有另一种骨髓疾病-中或高风险骨髓纤维化患者的治疗，包括原发性骨髓纤维化、真性红细胞增多性骨髓纤维化及原发性血小板增多性骨髓纤维化。鲁索替尼由特拉华州威尔明顿的Incyte公司上市销售。
Jakafi (ruxolitinib) Tablets
Company: Incyte Corporation
Application No.: 202192
Approval Date: 11/16/2011
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JAKAFI Rx
Generic Name and Formulations:
Ruxolitinib 5mg, 10mg, 15mg, 20mg, 25mg; tabs.
Company:
Incyte Corporation
Indications for JAKAFI:
Treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis.
Adult:
Doses may be given by NG tube if unable to swallow tabs. Platelets >200X109/L: initially 20mg twice daily. Platelets 100–200X109/L: initially 15mg twice daily. Platelets 50–<100X109/L: initially 5mg twice daily. May increase doses by 5mg twice daily to a max of 25mg twice daily; do not increase during the first 4 weeks of therapy and not more frequently than every 2 weeks. Discontinue treatment after 6 months if no reduction in spleen size or symptom improvement. Interrupt treatment if platelets <50X109/L or ANC <0.5X109/L. May restart after recovery of platelets (see full labeling for max allowable restarting doses). Consider dose reductions if platelets decrease but remain ≥50X109/L (see full labeling). Dose modifications for patients starting treatment with platelets 50–<100X109/L: see full labeling. Concomitant strong CYP3A4 inhibitors (see Interactions) or fluconazole ≤200mg: initially 10mg twice daily if platelets ≥100X109/L; if platelets 50–<100X109/L: initially 5mg twice daily. Other reductions, see full labeling. Moderate or severe renal impairment (CrCl 15–59mL/min) and platelets between 100–150X109/L: initially 10mg twice daily. ESRD (CrCl <15mL/min) on dialysis with platelets between 100–200X109/L: 15mg after dialysis session; if with platelets >200X109/L: 20mg after dialysis session. ESRD not requiring dialysis, moderate or severe renal impairment with platelets <100X109/L: avoid. Hepatic impairment with platelets between 100–150X109/L: initially 10mg twice daily; if platelets <100X109/L: avoid.
Children:
Not established.
Pharmacological Class:
Kinase inhibitor.
Warnings/Precautions:
Monitor for thrombocytopenia, anemia, neutropenia; withhold or reduce dose if occur. Obtain CBC and platelets before initiating therapy, every 2–4 weeks until doses are stabilized, and then as clinically indicated. Risk of serious bacterial, mycobacterial, fungal, and viral infections; evaluate and treat if signs/symptoms occur. Confirm resolution of active infections before starting. May exacerbate myelofibrosis following treatment interruption or discontinuation. Avoid abrupt cessation. Renal or hepatic impairment. Pregnancy (Cat.C). Nursing mothers: not recommended.
Interactions:
Avoid concomitant fluconazole doses >200mg daily. Potentiated by strong CYP3A4 inhibitors (eg, boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) and mild or moderate CYP3A4 inhibitors (eg, erythromycin). Antagonized by CYP3A4 inducers (eg, rifampin).
Adverse Reactions:
Thrombocytopenia, anemia, neutropenia, bruising, dizziness, headache, UTIs, weight gain, flatulence, progressive multifocal leukoencephalopathy (discontinue if occurs), herpes zoster, tuberculosis (monitor and test for latent infection).
How Supplied:
Tabs—60 |
