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; eva luate 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
Jakafi (ruxolitinib) Tablets
Company: Incyte Corporation
Application No.: 202192
Approval Date: 11/16/2011
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美国批准第一个药物Jakafi(ruxolitinib)治疗一种罕见骨髓病
2011年11月16日，美国食品药品监督管理局批准Jakafi (ruxolitinib)。是批准特异性治疗骨髓纤维化骨髓病患者的第一个药物。
骨髓纤维化是一种疾病，导致制造血细胞器官如肝和脾骨髓被瘢痕组织替代。此病标志为脾脏肿大，贫血，白血细胞和血小板减低，和骨髓纤维化-相关症状。症状包括疲乏，腹部不适，肋下疼痛，饱感(早饱)，肌肉和骨痛，瘙痒，和夜汗。
Jakafi，一种每天服药2次药丸，抑制酶被称为JAK 1和2 (Janus相关激酶)涉及调节血液和免疫学功能。JAK 1和2调节障碍伴随骨髓纤维化。
美国FDA药物评价和研究中心血液和肿瘤产品办公室主任Richard Pazdur, M.D.说：“Jakafi代表在肿瘤中详尽了解疾病特异性机制，允许药物靶向特异性分子通路的另一个实例”“临床试验导致这个批注集中在经常遇到的骨髓纤维化，包括脾脏肿大和疼痛患者的问题。”
在528例患者的两项临床试验中评价Jakafi的安全性和有效性。两项试验患者都是对可以得到骨髓纤维化治疗耐药或难治或对同种异体骨髓移植(即患者接受来自遗传上相似，但不一定相同供体的造血干细胞)不合格。所有患者有脾脏肿大和因疾病-相关症状的结果需要治疗。
在研究中被选择患者接受或Jakafi治疗，安慰剂(糖丸)或可得到的最佳治疗(羟基脲[hydroxyurea]，一种化疗药，或糖皮质激素)。有更大百分率的接受Jakafi患者，当与接受安慰剂或可得到最佳治疗患比较时，经受脾脏大小减低大于35百分率。相似地，接受Jakafia比接受安慰剂患者，有更大患者比例见到骨髓纤维化-相关症状，包括腹部不适，夜汗，瘙痒和骨或肌肉痛减低50%以上.
用Jakafi治疗患者见到最严重副作用包括血小板计数减低，贫血，疲乏，腹泻，气短(呼吸困难)，头痛，眩晕，和恶心。
Jakafi是在FDA的优先审评程序下被审评，即对可能提供显著进展超过可得到治疗的治疗或对当前没有适当治疗提供治疗加快6-个月审评药物的一种程序。
本治疗正在按处方药物用户费用法[Prescription Drug User Fee Act]下的目标日期2011年12月3日前被批准和已被指定为孤儿药物，确定疾病在美国影响人数少于200,000人。
批准日期：2011年11月16日； Jakafi由Wilmington, Del.Incyte Corp.公司制造。
