近日，美国食品和药物管理局（FDA）已批准Mayzent（siponimod），用于复发型多发性硬化症（MS）成人患者的治疗，包括活动性继发进展型多发性硬化症（SPMS）、复发缓解型多发性硬化症（RRMS）、临床孤立综合征（CIS）.
用药方面;患者不需要首次给药观察（FDO，开始治疗时进行心脏监测），除非有某些预先存在的心脏疾病。（注：CIS定义为神经系统症状的首次发作，持续至少24小时，由中枢神经系统炎症或脱髓鞘引起） 
批准日期：2019年3月26日 公司：诺华公司
MAYZENT（西尼莫德 [siponimod]）片剂，用于口服
美国最初批准：2019年
作用机制
Siponimod是一种鞘氨醇-1-磷酸（S1P）受体调节剂。 Siponimod以高亲和力结合S1P受体1和5.Siponimod阻断淋巴细胞从淋巴结中排出的能力，减少外周血中淋巴细胞的数量。 脂联素在多发性硬化症中发挥治疗作用的机制尚不清楚，但可能涉及淋巴细胞向中枢神经系统迁移的减少。
适应症和用法
MAYZENT是一种鞘氨醇1-磷酸受体调节剂，用于治疗复发性多发性硬化症（MS），包括临床表现
成人中的孤立综合征，复发缓解型疾病和活跃的继发性进展性疾病。
剂量和给药
在启动MAYZENT之前需要进行评估
治疗开始需要滴定
建议的维持剂量为2毫克
CYP2C9 *1/*3或* 2/*3基因型患者的推荐维持剂量为1mg
对于患有窦性心动过速，一级或二级[Mobitz I型]房室（AV）阻滞或心肌梗塞或心力衰竭病史的患者，建议进行首剂量监测。
剂量形式和强度
片剂：0.25毫克和2毫克
禁忌症
患有CYP2C9 *3/*3基因型的患者
在过去的6个月中，经历过心肌梗塞，不稳定性心绞痛，中风，TIA，需要住院治疗的失代偿性心力衰竭，或III/IV级心力衰竭。
存在Mobitz II型二度，三度房室传导阻滞，奥西斯窦综合征，除非患者有起搏器功能。
警告和注意事项
感染：MAYZENT可能会增加风险。在开始治疗之前获得完整的血液计数（CBC）。监测治疗期间的感染情况。不要从有活动性感染的患者开始。
黄斑水肿：建议在开始治疗前进行眼科评估，如果在服用MAYZENT时视力有任何变化，糖尿病和葡萄膜炎会增加风险。
缓慢性心律失常和房室传导延迟：MAYZENT可能导致心率短暂下降;在治疗开始时需要滴定。考虑静息心率与伴随的betablockeruse;获得心脏病专家咨询，同时使用其他降低心率的药物。
呼吸系统影响：可能导致肺功能下降。如果临床指示，评估肺功能（例如肺量计）。
肝损伤：在开始前获得肝酶结果。密切监测严重肝功能损害的患者。如果发生明显的肝损伤则停止。
血压升高（BP）：治疗期间监测血压。
胎儿风险：有生育潜力的女性应在停止使用后的10天内使用有效的感染。
不良反应
最常见的不良反应（发生率大于10％）是头痛，高血压和转氨酶升高。
要报告疑似不良反应，请致电1-888-669-6682联系NovartisPharmaceuticals Corporation或致电1-800-FDA-1088或www.fda.gov/medwatch联系FDA。
药物相互作用
疫苗：在使用MAYZENT治疗期间和治疗后4周内避免使用减毒活疫苗。
CYP2C9和CYP3A4抑制剂：增加了siponimod暴露;同时使用MAYZENT与中度CYP2C9和中度orstrong CYP3A4抑制剂不建议
CYP2C9和CYP3A4诱导剂：塞尼莫德暴露减少;不建议同时使用MAYZENT与中度CYP2C9和强CYP3A4诱导剂。
包装提供/存储和处理
提供
MAYZENT薄膜包衣片如下：
0.25毫克片剂：淡红色，未刻痕，圆形双凸面薄膜包衣片，斜边，一面凹凸不平
和另一边的'T'。
Starter Pack *-日历化泡罩钱包中12个0.25毫克片剂的吸塑卡........ NDC 0078-0979-12
此初学者包仅适用于接受2mg维持剂量的患者。
一瓶28片...................... NDC 0078-0979-50
2毫克片剂：淡黄色，未刻痕，圆形双凸面薄膜包衣片，带斜边，一面凹凸不平
和另一边的'II'。
一瓶30片................. NDC 0078-0986-15
存储和处理
未开封的容器
将未开封的MAYZENT 0.25 mg容器和2 mg薄膜包衣片放在2°C至8°C的冰箱中
（36°F至46°F）。
打开容器
存储打开的MAYZENT容器如下：
入门包/吸塑卡
启动包装中的MAYZENT 0.25毫克薄膜包衣片剂可在打开泡罩后在20°C至25°C（68°F至77°F）[参见USPC控制的室温]下储存长达1周。存放在原始容器中。
瓶子
将瓶装的0.25毫克和2毫克薄膜包衣片在打开瓶子后，可在20°C至25°C（68°F至77°F）[参见USPC控制室温]下保存长达1个月。
完整说明资料附件：
https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/mayzent.pdf
MAYZENT(siponimod)
INDICATION
MAYZENT(siponimod) is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
IMPORTANT SAFETY INFORMATION
Contraindications
Patients with a CYP2C9*3/*3 genotype
In the last 6 months, experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III/IV heart failure
Presence of Mobitz type II second-degree, third-degree atrioventricular block, or sick sinus syndrome, unless patient has a functioning pacemaker
Infections: MAYZENT may increase risk of infections with some that are serious in nature. Life-threatening and rare fatal infections have occurred.
Before starting MAYZENT, review a recent complete blood count (CBC) (ie, within 6 months or after discontinuation of prior therapy). Delay initiation of treatment in patients with severe active infections until resolved. Employ effective treatments and monitor patients with symptoms of infection while on therapy. Consider discontinuing treatment if patient develops a serious infection.
Cases of fatal cryptococcal meningitis (CM) were reported in patients treated with another sphingosine 1-phosphate (S1P) receptor modulator. Rare cases of CM have occurred with MAYZENT. If CM is suspected, MAYZENT should be suspended until cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated.
No cases of progressive multifocal leukoencephalopathy (PML) were reported in MAYZENT clinical trials; however, they have been observed in patients treated with another sphingosine 1-phosphate (S1P) receptor modulator and other multiple sclerosis (MS) therapies. If PML is suspected, MAYZENT should be discontinued.
Cases of herpes viral infection, including one case of reactivation of varicella zoster virus leading to varicella zoster meningitis, have been reported. Patients without a confirmed history of varicella zoster virus (VZV) or without vaccination should be tested for antibodies before starting MAYZENT. If VZV antibodies are not present or detected, then VZV immunization is recommended and MAYZENT should be initiated 4 weeks after vaccination.
Use of live vaccines should be avoided while taking MAYZENT and for 4 weeks after stopping treatment.
Caution should be used when combining treatment (ie, anti-neoplastic, immune-modulating, or immunosuppressive therapies) due to additive immune system effects.
Macular Edema: In most cases, macular edema occurred within 4 months of therapy. Patients with history of uveitis or diabetes are at an increased risk. Before starting treatment, an ophthalmic eva luation of the fundus, including the macula, is recommended and at any time if there is a change in vision. The use of MAYZENT in patients with macular edema has not been eva luated; the potential risks and benefits to the individual patient should be considered.
Bradyarrhythmia and Atrioventricular Conduction Delays: Prior to initiation of MAYZENT, an ECG should be obtained to determine if preexisting cardiac conduction abnormalities are present. In all patients, a dose titration is recommended for initiation of MAYZENT treatment to help reduce cardiac effects.
MAYZENT was not studied in patients who had:
In the last 6 months, experienced myocardial infarction, unstable angina, stroke, TIA, or decompensated heart failure requiring hospitalization
New York Heart Association Class II-IV heart failure
Cardiac conduction or rhythm disorders, including complete left bundle branch block, sinus arrest or sino-atrial block, symptomatic bradycardia, sick sinus syndrome, Mobitz type II second-degree AV-block or higher-grade AV-block (either history or observed at screening), unless patient has a functioning pacemaker
Significant QT prolongation (QTc greater than 500 msec)
Arrhythmias requiring treatment with Class Ia or Class III anti-arrhythmic drugs
Reinitiation of treatment (initial dose titration, monitoring effects on heart rate and AV conduction [ie, ECG]) should apply if ≥4 consecutive daily doses are missed.
Respiratory Effects: MAYZENT may cause a decline in pulmonary function. Spirometric eva luation of respiratory function should be performed during therapy if clinically warranted.
Liver Injury: Elevation of transaminases may occur in patients taking MAYZENT. Before starting treatment, obtain liver transaminase and bilirubin levels. Closely monitor patients with severe hepatic impairment. Patients who develop symptoms suggestive of hepatic dysfunction should have liver enzymes checked, and MAYZENT should be discontinued if significant liver injury is confirmed.
Increased Blood Pressure: Increase in systolic and diastolic pressure was observed about 1 month after initiation of treatment and persisted with continued treatment. During therapy, blood pressure should be monitored and managed appropriately.
Fetal Risk: Based on animal studies, MAYZENT may cause fetal harm. Women of childbearing potential should use effective contraception to avoid pregnancy during and for 10 days after stopping MAYZENT therapy.
Posterior Reversible Encephalopathy Syndrome (PRES): Rare cases of PRES have been reported in patients receiving a sphingosine 1-phosphate (S1P) receptor modulator. Such events have not been reported for patients treated with MAYZENT in clinical trials. If patients develop any unexpected neurological or psychiatric symptoms, a prompt eva luation should be considered. If PRES is suspected, MAYZENT should be discontinued.
Unintended Additive Immunosuppressive Effects From Prior Treatment or After Stopping MAYZENT: When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects.
Initiating treatment with MAYZENT after treatment with alemtuzumab is not recommended.
After stopping MAYZENT therapy, siponimod remains in the blood for up to 10 days. Starting other therapies during this interval will result in concomitant exposure to siponimod.
Lymphocyte counts returned to the normal range in 90% of patients within 10 days of stopping therapy. However, residual pharmacodynamic effects, such as lowering effects on peripheral lymphocyte count, may persist for up to 3-4 weeks after the last dose. Use of immunosuppressants within this period may lead to an additive effect on the immune system, and therefore, caution should be applied 3-4 weeks after the last dose of MAYZENT.
Severe Increase in Disability After Stopping MAYZENT: Severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of an S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping MAYZENT treatment, thus patients should be monitored upon discontinuation.
Most Common Adverse Reactions: Most common adverse reactions (>10%) are headache, hypertension, and transaminase increases.