英文药名：Ninlaro(Ixazomib Capsules)

中文药名：伊沙佐米胶囊

研发公司：武田（Takeda）
药品介绍
首个也是唯一的口服蛋白酶体抑制剂NINLARO(ixazomib)获美国FDA上市，用于治疗多发性骨髓瘤
近日，美国FDA批准NINLARO(ixazomib)是首个也是唯一的口服蛋白酶体抑制剂，其适应证是联合来那度胺和地塞米松用于治疗先前至少用过一种药物的多发性骨髓瘤患者。NINLARO每周一次口服，分别在28天周期的第1、8、15、28天给药。NINLARO目前正在欧洲药品管理局(EMA)审批中，并已获得人用药品委员会(CHMP)的加快评审。2014年，NINLARO还被美国FDA认可为用于复发或难治全身性轻链(AL)淀粉样变（一种相关的超级孤儿病）的突破性治疗药物。
作用机制
Ixazomib是一种可逆性蛋白体抑制剂。Ixazomib优先结合和抑制胰凝乳蛋白酶-样20S蛋白酶体的β 5亚单位的活性。
Ixazomib在体外诱导多发性骨髓瘤细胞系的凋亡。Ixazomib对来自多种以前治疗后，包括硼替佐米[bortezomib]，来那度胺，和地塞米松已复发患者的骨髓瘤细胞显示体外细胞毒性。在多发性骨髓瘤细胞系中Ixazomib和来那度胺的联用显示协同的细胞毒效应。在体内，在一种小鼠多发性骨髓瘤肿瘤异种移植模型ixazomib显示抗肿瘤活性。
适应证和用途
NINLARO是一个蛋白体抑制剂适用与来那度胺和地塞米松联用为有多发性骨髓瘤患者曽接受至少一种以前治疗的治疗。
剂量和给药方法
⑴  推荐起始剂量4 mg口服在28-天疗程的第1，8，和15天。
⑵  剂量应被服用食物前至少一小时或后至少2小时。
剂型和规格
胶囊：4mg，3mg，2.3mg
禁忌证
无。
警告和注意事项
⑴  血小板减少：治疗期间监视血小板计数至少每月和调整，当需要时。
⑵  胃肠道毒性：对严重腹泻，便秘，恶心,和呕吐，当需要时调整给药。
⑶  外周神经病变：监视患者外周神经病变的症状和调整给药，当需要时。
⑷  外周水肿：监视液体潴留。研究潜在原因，当适当。调整给药，当需要时。
⑸  皮肤反应：监视患者皮疹和调整给药，当需要时。
⑹  肝毒性：治疗期间监视肝酶。
⑺  胚胎胎儿毒性：NINLARO可能致胎儿危害。忠告生殖潜能女性和使用有效避孕。
不良反应
最常见不良反应(≥ 20%)是腹泻，便秘，血小板减少，外周神经病变，恶心，外周水肿，呕吐,和背痛。
药物相互作用
强CYP3A诱导剂：避免与NINLARO同时使用。
特殊人群中使用
⑴  肝受损：在有中度或严重肝受损患者减低NINLARO开始剂量至3mg。
⑵ 肾受损：有严重肾受损或肾病终末期需要透析患者减低NINLARO开始剂量至3mg。
⑶ 哺乳：终止哺乳。
完整说明书附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fcef9088-ebab-4bd8-933f-c35f9c8bd50b

------------------------------------------------------
注：以下产品美国上市，不同各和不同价格，采购者以咨询为准。
------------------------------------------------------
NINLARO 2.3MG CAP BLSTR DPSH 3/PAC  IXAZOMIB  NINLARO DIRECT  63020-0078-02
NINLARO 3MG CAP BLSTR DPSH 3/PAC  IXAZOMIB  NINLARO DIRECT  63020-0079-02            
NINLARO 4MG CAP BLSTR DPSH 3/PAC  IXAZOMIB  NINLARO DIRECT  63020-0080-02            
NINLARO CAP 2.3MG UD1X3 DS  IXAZOMIB CITRATE  ICS/NINLARO DIRECT  63020-0078-02
NINLARO CAP 3MG UD1X3 DS IXAZOMIB CITRATE  ICS/NINLARO DIRECT  63020-0079-02
NINLARO CAP 4MG UD1X3 DS  IXAZOMIB CITRATE  ICS/NINLARO DIRECT  63020-0080-02

NINLARO(ixazomib Capsules)
Brand name: Ninlaro
Generic name: ixazomib
Dosage form: Capsules
Company: Takeda Pharmaceuticals U.S.A., Inc.
IMPORTANT SAFETY INFORMATION AND INDICATION
WARNINGS AND PRECAUTIONS
Thrombocytopenia has been reported with NINLARO® (ixazomib). During treatment, monitor platelet counts at least monthly, and consider more frequent monitoring during the first three cycles. Manage thrombocytopenia with dose modifications and platelet transfusions as per standard medical guidelines. Adjust dosing as needed. Platelet nadirs occurred between Days 14-21 of each 28-day cycle and typically recovered to baseline by the start of the next cycle.
Gastrointestinal Toxicities, including diarrhea, constipation, nausea and vomiting, were reported with NINLARO and may occasionally require the use of antidiarrheal and antiemetic medications, and supportive care. Diarrhea resulted in the discontinuation of one or more of the three drugs in 1% of patients in the NINLARO regimen and<1% of patients in the placebo regimen. Adjust dosing for severe symptoms.
Peripheral Neuropathy (predominantly sensory) was reported with NINLARO. The most commonly reported reaction was peripheral sensory neuropathy(19% and 14% in the NINLARO and placebo regimens, respectively). Peripheral motor neuropathy was not commonly reported in either regimen(<1%). Peripheral neuropathy resulted in discontinuation of one or more of the three drugs in 1% of patients in both regimens. Monitor patients for symptoms of peripheral neuropathy and adjust dosing as needed.
Peripheral Edema was reported with NINLARO. Monitor for fluid retention. Investigate for underlying causes when appropriate and provide supportive care as necessary. Adjust dosing of dexamethasone per its prescribing information or NINLARO for Grade 3 or 4 symptoms.
Cutaneous Reactions: Rash, most commonly maculo-papular and macular rash, was reported with NINLARO. Rash resulted in discontinuation of one or more of the three drugs in < 1% of patients in both regimens. Manage rash with supportive care or with dose modification.
Hepatotoxicity has been reported with NINLARO. Drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic and hepatotoxicity have each been reported in < 1% of patients treated with NINLARO. Events of liver impairment have been reported (6% in the NINLARO regimen and 5% in the placebo regimen). Monitor hepatic enzymes regularly during treatment and adjust dosing as needed.
Embryo-fetal Toxicity: NINLARO can cause fetal harm. Women should be advised of the potential risk to a fetus, to avoid becoming pregnant, and to use contraception during treatment and for an additional 90 days after the final dose of NINLARO. Women using hormonal contraceptives should also use a barrier method of contraception.
ADVERSE REACTIONS
The most common adverse reactions(≥ 20%) in the NINLARO regimen and greater than the placebo regimen, respectively, were diarrhea (42%, 36%), constipation (34%, 25%), thrombocytopenia (78%, 54%; pooled from adverse events and laboratory data), peripheral neuropathy (28%, 21%), nausea (26%, 21%), peripheral edema (25%, 18%), vomiting (22%, 11%), and back pain (21%, 16%). Serious adverse reactions reported in ≥ 2% of patients included thrombocytopenia(2%) and diarrhea(2%).
SPECIAL POPULATIONS
Hepatic Impairment: Reduce the NINLARO starting dose to 3 mg in patients with moderate or severe hepatic impairment.
Renal Impairment: Reduce the NINLARO starting dose to 3 mg in patients with severe renal impairment or end-stage renal disease requiring dialysis. NINLARO is not dialyzable.
Lactation: Advise nursing women not to breastfeed during treatment with NINLARO and for 90 days after the last dose.
DRUG INTERACTIONS: Avoid concomitant administration of NINLARO with strong CYP3A inducers.
INDICATION
NINLARO is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.