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Daurismo(glasdegib Tablets)

2018-11-24 07:48:47 作者：新特药房来源：互联网浏览次数：39 文字大小：【大】【中】【小】

简介：近日，美国食品和药物管理局（FDA）批准靶向抗癌药Daurismo（glasdegib）上市，联合低剂量阿糖胞苷（LD-AC）化疗，一线治疗新确诊的2类急性髓性白血病（AML）成人患者，具体为：（1）年龄在75岁及以上的老 ...

关键字：格拉斯吉布片 glasdegib 商品名DAURISMO 靶向抗癌药急性髓细胞白血病

近日，美国食品和药物管理局（FDA）批准靶向抗癌药Daurismo（glasdegib）上市，联合低剂量阿糖胞苷（LD-AC）化疗，一线治疗新确诊的2类急性髓性白血病（AML）成人患者，具体为：（1）年龄在75岁及以上的老年AML患者；（2）因同时存在其他疾病而不适合进行强化诱导化疗的AML成人患者。
此次批准，使Daurismo成为首个也是唯一一个获FDA批准治疗AML的Hedgehog信号通路抑制剂，将为因年龄或其他疾病无法接受强化化疗的难治性患者群体提供一个大幅改善总体生存的重要治疗选择。
批准日期：2018年11月21日 开发公司:辉瑞
DAURISMO(格拉斯吉布[glasdegib])片剂,供口服使用
首次美国批准：2018
警告：
胚胎-胎儿毒性完全处方信息，完整的框警告。
当给孕妇服用DAURISMO可导致胚胎-胎儿死亡或严重出生缺陷。DuriSimo是动物胚胎毒性、胎儿毒性和致畸性。
在DAURISMO治疗开始前，对有生育潜力的女性进行妊娠测试。建议有生育潜力的女性在使用DAURISMO治疗期间和最后一剂量后至少30天内使用有效的避孕措施。
建议男性在使用DAURISMO治疗期间以及在最后一次给药后至少30天内通过精液和避孕套与怀孕伴侣或具有生育潜力的女性伴侣接触避孕套的潜在风险，以避免潜在的药物接触。
作用机理
Glasdegib是Hedgehog通路的抑制剂。Glasdegib结合并抑制与刺猬信号转导有关的平滑的膜蛋白。
在小鼠异种移植人AML模型中，glasdegib联合小剂量阿糖胞苷比单独应用glasdegib或小剂量阿糖胞苷更能抑制肿瘤的增大，降低骨髓中CD45+/CD33+细胞的百分率。
适应症及用法
DAURISMO是一种刺猬途径抑制剂，联合小剂量阿糖胞苷，用于治疗成人≥75岁的新诊断急性髓细胞白血病（AML）或具有不能使用强化诱导化疗的生态病症。
使用限制：DAURISMO尚未在伴有严重肾损害或中度至重度肝损害的患者中进行研究。
剂量与给药
推荐剂量：口服100mg，每日1次。
剂型和强度
片剂：100mg，25mg。
禁忌症
没有。
警告和注意事项
献血：建议患者在最后一次给药后至少30天内不要用DAURISMO进行献血或采血治疗。
QTc间期延长：监测心电图和电解质。IFQTc发生延长，中断治疗与DuriSimo。
不良反应
最常见的不良反应（发生率≥20%）是贫血、疲劳、出血、发热、中性粒细胞减少、肌肉骨骼疼痛、恶心、水肿、血小板减少、呼吸困难、食欲减退、吞咽困难、粘膜炎、便秘和皮疹。
药物相互作用
强CYP3A4抑制剂：考虑非强CYP3A抑制剂的替代疗法，或监测不良反应风险增加，包括QTc间期延长。
强CYP3A4诱导剂：避免与DuriSo同时使用。
QTC延长用药：避免与达鲁司莫联合用药。如果联合用药是不可避免的，监测QT间期延长的风险增加。
在特定人群中的使用
哺乳期：建议妇女不要母乳喂养。
包装供应/储存和搬运
DAURISMO提供以下强度和封装配置：
DAURISMO薄膜包衣片
封装配置片剂强度（毫克）
30片/瓶        100毫克   NDC： 0069-1531-30
描述
100mg强度:11 mmround，浅橙色覆膜平板，一面印有“Pfizer”字样，另一面印有“GLS100”字样
60片/瓶       25毫克    NDC： 0069-0298-60
25mg强度:7mmround，黄色覆膜平板，一面印有“Pfizer”字样，另一面印有“GLS25”字样
于20o C至25o C (68o F至77o F)存放;允许在15度到30度之间(59度到86度)旅行。
完整资料附件：
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210656s000lbl.pdf
U.S. FDA APPROVES DAURISMO™ (GLASDEGIB) FOR ADULT PATIENTS WITH NEWLY-DIAGNOSED ACUTE MYELOID LEUKEMIA (AML) FOR WHOM INTENSIVE CHEMOTHERAPY IS NOT AN OPTION
DAURISMO is the first and only Hedgehog pathway inhibitor approved for the treatment of AML
In a randomized Phase 2 trial, DAURISMO plus low-dose chemotherapy significantly improved median overall survival in patients who were not able to receive intensive chemotherapy due to age or comorbidities – a difficult-to-treat patient population
U.S. Food and Drug Administration (FDA) approved DAURISMO™ (glasdegib), a once-daily oral medicine, for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adult patients who are 75 years or older or who have comorbidities that preclude use of intensive induction chemotherapy. DAURISMO is taken in combination with low-dose cytarabine (LDAC), a type of chemotherapy. DAURISMO has not been studied in patients with severe renal impairment or moderate-to-severe hepatic impairment.
AML is a rapidly progressing bone marrow cancer with poor survival rates compared to other leukemias.2 The standard of care for people with AML is intensive chemotherapy; however, for many elderly patients with AML, as well as those who have certain health conditions prior to receiving their diagnosis, intensive treatment is not an option.3 Historically, a majority of these individuals do not receive treatment and face a poor prognosis.
“As our second medicine approved in the last 14 months for patients with acute myeloid leukemia, DAURISMO reinforces our commitment to delivering new medicines to patients living with some of the most difficult-to-treat cancers, especially those for which there are limited treatment options available,” said Andy Schmeltz, Global President, Pfizer Oncology. “We are proud to now offer these patients for whom intensive chemotherapy is not an option a new oral medicine, taken in combination with low-dose chemotherapy, that may improve their chances of survival.”
DAURISMO is the first and only FDA-approved Hedgehog pathway inhibitor for AML. The Hedgehog signaling pathway plays an essential role in embryogenesis, the process by which human embryos are developed. In adults, however, abnormal activation of this pathway is thought to contribute to the development and persistence of cancer stem cells. Preclinical studies have shown that disruption of this pathway can impair the development and survival of these cancer stem cells.5,6
“The randomized Phase 2 study, which formed the basis for today’s approval, included patients with cardiac disease or mild to moderate kidney disease, who are often excluded from clinical trials,” said Jorge Cortes, M.D., deputy chair and professor of medicine in the Department of Leukemia, University of Texas, MD Anderson Cancer Center. “In the trial, DAURISMO plus low-dose chemotherapy reduced the risk of death during the study period by 54 percent compared to chemotherapy alone. This provides a much-needed treatment for those patients for whom intensive chemotherapy is not an option.”
In the pivotal, randomized, international Phase 2 BRIGHT 1003 trial, 115 patients with newly diagnosed AML were randomized 2:1 to receive DAURISMO plus LDAC or LDAC alone. Of the 77 patients treated with DAURISMO plus LDAC, more than half (51%, 39 patients) had secondary AML, or AML that develops as a result of prior blood/bone marrow conditions or previous anticancer therapy. Eleven of the 39 patients with secondary AML received prior treatment with a hypomethylating agent; historically, the prognosis is poor for these patients and treatment options have been limited to clinical trials or palliative care. Median overall survival was 8.3 months (95% CI: 4.4,12.2) for patients treated with DAURISMO plus LDAC compared with 4.3 months (95% CI: 1.9, 5.7) for patients treated with LDAC alone. This difference represented a 54 percent reduction in the risk of death for patients treated with DAURISMO plus LDAC (HR: 0.46, 95% CI: 0.30, 0.71, one-sided p-value 0.0002).
The U.S. labeling for DAURISMO includes a boxed warning for embryo-fetal toxicity. The most frequently (≥20% of patients) reported adverse events (AEs) in patients treated with DAURISMO plus LDAC compared to LDAC alone in first 90 days of therapy were anemia (43% vs 42%), fatigue (36% vs 32%), hemorrhage (36% vs 42%), febrile neutropenia (31% vs 22%), musculoskeletal pain (30% vs 17%), nausea (29% vs 12%), edema (30% vs 20%), thrombocytopenia (30% vs 27%), dyspnea (23% vs 24%), decreased appetite (21% vs 7%), dysgeusia (21% vs 2%), mucositis (21% vs 12%), constipation (20% vs 12%) and rash (20% vs 7%).1 Serious adverse reactions were reported in 79% of patients treated in the DAURISMO plus LDAC arm. The most common (≥5%) serious adverse reactions in patients receiving DAURISMO plus LDAC were febrile neutropenia (29%), pneumonia (23%), hemorrhage (12%), anemia (7%) and sepsis (7%).1
“DAURISMO, a Hedgehog pathway inhibitor, was discovered in Pfizer laboratories and exemplifies our continued commitment to developing medicines that have the potential to advance cancer therapeutics,” said Mace Rothenberg, M.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “We are delighted by today’s approval of DAURISMO by the FDA, and are working to gain greater understanding of its role in treating patients with acute myeloid leukemia. The ongoing Phase 3 BRIGHT trials are evaluating DAURISMO in combination with other agents commonly used to treat patients with acute myeloid leukemia, in an effort to understand the full potential of this medicine against this aggressive leukemia.”
Pfizer is committed to ensuring that patients who are prescribed DAURISMO have access to this innovative therapy. Patients in the U.S. have access to Pfizer Oncology Together™, which offers personalized support and financial assistance resources to help patients access their prescribed Pfizer Oncology medications.
IMPORTANT DAURISMO SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION
WARNING: EMBRYO-FETAL TOXICITY: DAURISMO can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. DAURISMO is embryotoxic, fetotoxic, and teratogenic in animals. Conduct pregnancy testing in females of reproductive potential prior to initiation of DAURISMO treatment. Advise females of reproductive potential to use effective contraception during treatment with DAURISMO and for at least 30 days after the last dose. Advise males of the potential risk of DAURISMO exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential during treatment with DAURISMO and for at least 30 days after the last dose to avoid potential drug exposure.
Blood Donation: Advise patients not to donate blood or blood products while taking DAURISMO and for at least 30 days after the last dose, because their blood or blood products might be given to a female of reproductive potential.
QTc Interval Prolongation: Patients treated with DAURISMO can develop QTc prolongation and ventricular arrhythmias, including ventricular fibrillation and ventricular tachycardia. Monitor electrocardiograms (ECGs) and electrolytes. Concomitant use of DAURISMO with drugs known to prolong the QTc interval and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. In patients with congenital long QT syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring is recommended. Interrupt DAURISMO if QTc interval is >500 ms and discontinue permanently for patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.
Adverse Reactions: Most common adverse reactions (incidence ≥20%) are anemia, fatigue, hemorrhage, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, and rash.
Drug Interactions: Co-administration with strong CYP3A4 inhibitors increased DAURISMO plasma concentrations, which may increase the risk of adverse reactions including QTc interval prolongation. Consider alternative therapies that are not strong CYP3A4 inhibitors during treatment with DAURISMO and monitor patients for increased risk of adverse reactions including QTc interval prolongation. Strong CYP3A4 inducers should be avoided due to decreased DAURISMO plasma concentrations, which may reduce efficacy.
Lactation: Because of the potential for serious adverse reactions from DAURISMO in a breastfed child, advise women who are taking DAURISMO not to breastfeed or provide breast milk to infants or children during treatment and for at least 30 days after the last dose.
About DAURISMO(glasdegib)
DAURISMO is a once-daily oral Hedgehog pathway inhibitor, taken in combination with LDAC, for the treatment of newly diagnosed AML in adult patients who are 75 years or older or who have comorbidities that preclude use of intensive induction chemotherapy.1 DAURISMO has not been studied in patients with severe renal impairment or moderate-to-severe hepatic impairment. As an oral therapy, which is taken with subcutaneous LDAC, DAURISMO offers the flexibility for patients to receive this treatment regimen at home or in the outpatient setting.