近日，美国FDA批准Ninlaro（ixazomib）与其它药物合并用于治疗既往至少接受过一种治疗的多发性骨髓瘤患者。 FDA药物评价和研究中心Richard Pazdur博士指出，当今社会需要研究学者共同合作研发治疗多发性骨髓瘤的新的治疗方法。Ninlaro是今年FDA批准的用于治疗多发性骨髓瘤的第3种药物，通过口服的方式，可减缓肿瘤的进展。今年FDA批准的其他2种药物为Farydak和Darzalex。  Ninlaro是一种口服蛋白酶体抑制剂，通过阻止多发性骨髓瘤细胞酶的合成，阻碍肿瘤细胞的成长和增殖。FDA批准它可与Revlimid和地塞米松联合服用以增强效果。  Ninlaro(ixazomib)胶囊，供口服使用。推荐起始剂量4mg口服在28-天疗程的第1，8，和15天。剂量应被服用食物前至少一小时或后至少2小时。 批准日期：2015年11月20日  公司：武田制药 Ninlaro(ixazomib)胶囊，供口服使用。 美国初次批准：2015 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。 适应症和用途 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。 剂型和规格 胶囊：4mg，3mg，和2.3mg。 剂量和给药方法 ⑴推荐起始剂量4mg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 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。 --------------------------------------------------- 注：以下产品美国包装上市，采购以咨询为准 --------------------------------------------------- NINLARO 2.3MG CAP BLSTR DPSH 3/PAC  IXAZOMIB     63020-0078-02  NINLARO 3MG CAP BLSTR DPSH 3/PAC  IXAZOMIB     63020-0079-02  NINLARO 4MG CAP BLSTR DPSH 3/PAC  IXAZOMIB     63020-0080-02  NINLARO® (ixazomib) capsules, the first and only oral proteasome inhibitor, are now available in the United States. 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. Takeda Pharmaceutical Company Limited (TSE: 4502) recently received U.S. Food and Drug Administration (FDA) approval for NINLARO, four months prior to its Priority Review PDUFA date. NINLARO is a once-weekly pill for three weeks of a four week cycle. INDICATION NINLARO® (ixazomib) is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. WARNINGS AND PRECAUTIONS •Thrombocytopenia has been reported with NINLARO. 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 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fcef9088-ebab-4bd8-933f-c35f9c8bd50b