Department of Pharmacy, Yale New Haven Hospital, New Haven, Connecticut, USA.
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Drugs Today (Barc). 2020 Dec;56(12):755-768. doi: 10.1358/dot.2020.56.12.3230206.
Fedratinib hydrochloride is a selective Janus kinase 2 (JAK2) inhibitor approved by the U.S. Food and Drug Administration (FDA) in August 2019 for intermediate- 2 or high-risk primary or secondary myelofibrosis. The approval of this novel oral agent was based on the phase II and III JAKARTA-2 and JAKARTA trials, which both showed significant reduction in splenomegaly and myelofibrosis symptom burden. The most common adverse effects associated with fedratinib include anemia, gastrointestinal symptoms and elevation in liver transaminases. Early clinical trial data was concerning for an increased incidence of Wernicke's encephalopathy (WE), which led the FDA to place a clinical hold on further drug development. However, upon further investigation it was determined that there was no clear evidence that fedratinib causes WE, and the clinical hold was lifted in 2017. This inclusive review provides insight into the pharmacology, safety and efficacy, and future direction of fedratinib use in myeloproliferative neoplasms.
盐酸费德替尼是一种选择性 Janus 激酶 2（JAK2）抑制剂，于 2019 年 8 月获得美国食品和药物管理局（FDA）批准，用于治疗中-2 或高危原发性或继发性骨髓纤维化。该新型口服药物的批准基于 II 期和 III 期 JAKARTA-2 和 JAKARTA 试验，这两项试验均显示脾脏肿大和骨髓纤维化症状负担显著减轻。与费德替尼相关的最常见不良反应包括贫血、胃肠道症状和肝转氨酶升高。早期临床试验数据令人担忧的是威尼克脑病（WE）发病率增加，这导致 FDA 对进一步的药物开发实施临床搁置。然而，进一步的调查表明，没有明确证据表明费德替尼会导致 WE，并且临床搁置于 2017 年解除。本综述全面介绍了费德替尼在骨髓增生性肿瘤中的药理学、安全性和疗效以及未来应用方向。
