近日，美国FDA批准TAVALISSE(fostamatinib disodium hexahydrate)用于对之前治疗缓解不佳的成年慢性免疫性血小板减少症（ITP）患者血小板减少的治疗。TAVALISSE是一种口服的脾脏酪氨酸激酶(SYK)抑制剂，通过阻止血小板的破坏来应对疾病的潜在自身免疫原因，为成年慢性ITP患者提供了一个重要的新的治疗方案。
批准日期：2018年4月17日 公司：Rigel Pharmaceuticals
TAVALISSE（fostamatinib disodium hexahydrate）片剂，用于口服
美国最初批准：2018年
作用机制
Fostamatinib是一种酪氨酸激酶抑制剂，具有抗脾脏酪氨酸激酶（SYK）的活性。 fostamatinib的主要代谢产物R406抑制Fc激活受体和B细胞受体的信号转导。 fostamatinib代谢物R406减少抗体介导的血小板破坏。
适应症和用法
TAVALISSE是一种激酶抑制剂，适用于治疗慢性免疫性血小板减少症（ITP）患者的血小板减少症，该患者对既往治疗的反应不足。
剂量和给药
每天两次口服100毫克TAVALISSE，有或没有食物。4周后，如果需要，每天两次增加至150毫克，以达到必要的血小板计数至少50×109/L，以降低出血风险。
使用剂量减少，中断治疗或停药来管理不良反应。
如果血小板计数没有增加到足以避免临床上重要出血的水平，则在治疗12周后停止TAVALISSE。
剂量形式和强度
片剂：100mg，150mg
禁忌症
没有。
警告和注意事项
高血压：每2周监测血压直至稳定，然后每月监测一次。使用标准抗高血压治疗来控制高血压，如果需要，可以中断，减少或停止TAVALISSE。
肝毒性：每月监测LFT。如果LFT级别升高，则中断，减少或停止TAVALISSE。
腹泻：采取支持措施控制腹泻。如果腹泻变得严重，请中断，减少或停止TAVALISSE。
中性粒细胞减少症：每月监测ANC，并进行感染。如果中性粒细胞计数降至1.0×109/L以下，则中断，减少或停止TAVALISSE。
胚胎-胎儿毒性：TAVALISSE会导致胎儿伤害。告知患有胎儿潜在风险并使用有效避孕措施的患者。
不良反应
最常见的不良反应（≥5％和安慰剂以上）是腹泻，高血压，恶心，呼吸道感染，头晕，ALT/AST增加，皮疹，腹痛，疲劳，胸痛和中性粒细胞减少。
药物相互作用
强CYP3A4抑制剂：与强CYP3A4抑制剂同时使用可增加R406（主要活性代谢物）的暴露。
强CYP3A4诱导剂：不建议同时使用。
用于特定人群
怀孕：建议女性患胎儿的风险。
哺乳期：建议女性不要母乳喂养。
包装提供/存储和处理
TAVALISSE 100毫克片剂为圆形，双凸面，橙色，薄膜包衣片，一面凹凸，“背面”为“R”。
TAVALISSE 150毫克片剂为椭圆形，双凸面，橙色，薄膜包衣片，一面压印“150”，反面压印“R”。
100毫克片剂：60瓶装，2个干燥剂罐NDC 71332-001-01
150毫克片剂：60瓶装，2个干燥剂罐NDC 71332-002-01
储存于室温，20°C至25°C（68°F至77°F）; 允许的偏差在15°C至30°C（59°F至86°F）之间[见USP受控室温]。 不要去除干燥剂。

完整说明资料附件：
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=21149cc3-049b-43e2-b141-c9499160556c
TAVALISSE is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had
TAVALISSETM (fostamatinib disodium hexahydrate), an oral spleen tyrosine kinase(SYK) inhibitor for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.
ITP is an autoimmune disease where the immune system attacks and destroys platelets in the blood, resulting in abnormally low platelet counts. There are approximately 60,000 patients with adult primary ITP in the U.S., and it qualifies as an orphan disease.
Important Safety Information
Warnings and Precautions
Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to >3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE.
Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients.  Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.
TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.
Drug Interactions
Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (e.g., rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (e.g. digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.
Adverse Reactions
Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).
Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.