首个治骨髓纤维化药获准上市
11月16日，美国食品与药物管理局（FDA）批准Jakafi(ruxolitinib)上市，这是第一个获准的专门治疗骨髓纤维化的药物。
骨髓纤维化是骨髓被瘢痕组织替换，导致血细胞在肝脏和脾脏生成，该病的特征是脾肿大、贫血、白细胞和血小板减少，以及骨髓纤维化的相关症状，包括乏力、腹部不适、肋骨下疼痛、肌肉骨骼疼痛、瘙痒和盗汗。
Jakafi（每次1片，每日2次）抑制JAK 1和JAK2酶（Janus相关激酶），该酶涉及调节血液和免疫功能。骨髓纤维化与JAK 1和JAK2失调相关。
美国FDA药物研究与评价中心血液和肿瘤产品办公室主任理查（Richard Pazdur）说：“Jakafi代表了肿瘤学领域一种日渐增多的趋势，即通过对疾病机制详细的科学理解，研发出针对特殊分子通路的药物。促使该药获准的临床试验，主要关注了骨髓纤维化病人常有的脾肿大和疼痛。”
两项纳入528例病人的临床试验，评价了Jakafi的安全性和有效性。参加两项试验的病人都对现有骨髓纤维化疗法耐药或治疗无效，或不适合骨髓移植治疗。所有病人均有脾肿大。
病人被选择接受Jakafi、安慰剂或现有的最好治疗（化疗药羟基脲或糖皮质激素）。与其他两组相比，Jakafi组脾脏缩小35%以上病人的比例更大。同样，与安慰剂组相比，Jakafi组骨髓纤维化症状减少50%以上的病人比例更大，这些症状包括腹部不适、盗汗、瘙痒、骨骼或肌肉痛等。
Jakafi最严重的副作用包括血小板减少、贫血、乏力、腹泻、气短、头痛、头晕和恶心。Jakafi通过FDA的优先审查程序获准。
JAKAFI(ruxolitinib phosphate tablets)
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 Dose for JAKAFI:
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 4wks of therapy and not more frequently than every 2wks. Discontinue treatment after 6mos if no reduction in spleen size or symptom improvement. Interrupt treatment if platelets <50X109/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: initially 10mg twice daily if platelets ≥100X109/L; if platelets <100X109/L: avoid. 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's Dose for JAKAFI:
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. Renal or hepatic impairment. Pregnancy (Cat. C). Nursing mothers: not recommended.

Interactions:
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.

How Supplied:
Tabs—60