奥拉帕尼片Lynparza Tablets 100mg(olaparib)

奥拉帕尼片Lynparza Tablets 100mg(olaparib)

药店国别:

产地国家:美国

处方药:是

所属类别: 100毫克/片 60片/瓶

包装规格: 100毫克/片 60片/瓶

计价单位:瓶

生产厂家中文参考译名:

生产厂家英文名:AstraZeneca/Merck

原产地英文商品名:Lynparza 100mg/tablets 60tablets/bottle

原产地英文药品名:olaparib

中文参考商品译名:Lynparza口服片剂 100毫克/片 60片/瓶

中文参考药品译名:奥拉帕尼

曾用名:

简介:近日,美国食品和药物管理局(FDA)批准了PARP抑制剂LYNPARZA(olaparib 中文名:奥拉帕尼)如下:LYNPARZA片剂的新用途,用于对复发性,上皮性卵巢癌,输卵管癌或原发性腹膜癌患者进行维持治疗,这些患者对铂类化疗有完全或部分反应,无论BRCA状态如何;LYNPARZA片剂的新用途(每日两次2片),而不是胶囊(8粒,每日两粒);LYNPARZA片剂现在也表明(从目前加速批准转换)用于成年患有有害或疑似有害生殖系BRCA突变(gBRCA)晚期卵巢癌的患者,这些患者已接受过三次或更多次化疗前的治疗;根据FDA批准的伴随诊断选择用于该适应症的患者进行治疗。批准日期:2017年8月17日 公司:阿斯利康LYNPARZA(奥拉帕尼[olaparib])片剂,用于口服美国最初批准

作用机制:

Lynparza是聚(ADP-核糖)聚合酶(PARP)酶的抑制剂,包括PARP1,PARP2和PARP3。PARP酶参与正常细胞功能,例如DNA转录和DNA修复。Olaparib已经显示出在体外抑制选择的肿瘤细胞系的生长并且在人癌症的小鼠异种移植模型中减少肿瘤生长,作为单一疗法或基于铂的化学疗法。在用olaparib处理后增加的细胞毒性和抗肿瘤活性在细胞系和小鼠肿瘤模型中被注意到,其中BRCA和非BRCA蛋白缺陷参与DNA损伤的同源重组修复(HRR)并与铂反应相关。 体外研究表明,奥拉帕尼诱导的细胞毒性可能涉及抑制PARP酶活性和增加PARP-DNA复合物的形成,导致DNA损伤和癌细胞死亡。

适应症和用法:

Lynparza是一种聚(ADP-核糖)聚合酶(PARP)抑制剂,表明:

卵巢癌•用于对有害或疑似有害生殖系统或体细胞BRCA突变(g BRCAm或sBRCAm)晚期上皮卵巢,输卵管或原发性腹膜癌的成人患者进行维持治疗,这些患者对一线铂类化疗完全或部分应答。选择患有g BRCAm晚期上皮卵巢,输卵管或原发性腹膜癌的患者,根据FDA批准的Lynparza伴随诊断进行治疗。

•用于复发上皮性卵巢癌,输卵管癌或原发性腹膜癌的成人患者的维持治疗,这些患者对铂类化疗有完全或部分反应。

•用于治疗患有有害或疑似有害生殖系统的BRCA突变(g BRCAm)晚期卵巢癌的成年患者,这些患者已接受过三次或更多次化疗前的治疗。根据FDA批准的Lynparza伴随诊断选择患者进行治疗。

乳腺癌•对于在新辅助,辅助或转移性环境中接受化疗治疗的有害或疑似有害g BRCAm,人表皮生长因子受体2(HER2)阴性转移性乳腺癌的患者。激素受体(HR)阳性乳腺癌患者应该接受先前的内分泌治疗或被认为不适合进行内分泌治疗。根据FDA批准的Lynparza伴随诊断选择患者进行治疗。

剂量和给药:

•推荐的片剂剂量为300毫克,每天口服两次,有或没有食物。

•对于不良反应,请考虑剂量中断或剂量减少。

•对于中度肾功能损害(CLcr 31-50 mL/min),每日两次减少剂量至200 mg。

剂量形式和强度片剂:

150mg,100mg

禁忌症:

没有。

警告和注意事项:

•骨髓增生异常综合征/急性髓性白血病(MDS/AML):在接触Lynparza单药治疗的患者中发生率<1.5%且大多数事件都有致命的结果。在基线和之后每月监测患者的血液毒性。如果确认MDS / AML,则停止。

•肺炎:在接触Lynparza的患者中发生率<1%,有些病例是致命的。怀疑是肺炎的中断治疗。如果确诊肺炎则停止。

•胚胎-胎儿毒性:Lynparza可导致胎儿伤害。建议胎儿的潜在风险并使用有效的避孕措施。

不良反应:

•临床试验中最常见的不良反应(≥10%)为恶心,乏力(包括虚弱),贫血,呕吐,腹痛,头晕,腹泻,中性粒细胞减少,白细胞减少,鼻咽炎/上呼吸道感染/流感,呼吸道感染,关节痛/肌痛,味觉障碍,头痛,消化不良,食欲减退,便秘和口腔炎。

•最常见的实验室异常(≥25%)是血红蛋白减少,平均红细胞体积增加,淋巴细胞减少,白细胞减少,绝对中性粒细胞计数减少,血清肌酐增加和血小板减少。

药物相互作用:

•CYP3A抑制剂:避免同时使用强效或中度CYP3A抑制剂。如果不能避免抑制剂,减少奥拉帕尼剂量。

•CYP3A诱导剂:避免同时使用强效或中度CYP3A诱导剂,因为可能会降低疗效。

用于特定人群哺乳期:

建议女性不要母乳喂养。

包装提供/存储和处理提供:

Lynparza有150毫克和100毫克片剂。

•150毫克片剂:绿色至绿色/灰色,椭圆形,双凸面,薄膜包衣片,一面凹陷’OP150’,背面凹面平整,有:瓶装60粒(NDC 0310-0679-60)瓶装120片(NDC 0310-0679-12)。•100毫克片剂:黄色至深黄色,椭圆形,双凸面,薄膜包衣片,一面凹陷’OP100’,另一面凹凸,有:瓶装60粒(NDC 0310-0668-60)和瓶装120片(NDC 0310-0668-12)。

存储:

储存温度为20ºC至25ºC(68ºF至77ºF),允许偏差为15ºC至30ºC(59ºF至86ºF)[见USP受控室温]。 存放在原瓶中以防潮。

奥拉帕尼片英文版说明书:

(olaparib) RECEIVES ADDITIONAL FDA APPROVAL IN THE US FOR OVARIAN CANCERLYNPARZA’s new tablet formulation approved as maintenance treatment for women with recurrent ovarian cancer regardless of BRCA-mutation statusLYNPARZA tablets also indicated in BRCA-mutated ovarian cancer beyond the third-line settingAstraZeneca and Merck & Co., Inc., (Merck: known as MSD outside the U.S. and Canada) today announced that the US Food and Drug Administration (FDA) has granted approval for the PARP inhibitor, LYNPARZA® (olaparib), as follows:•New use of LYNPARZA tablets as a maintenance treatment of adult patients with recurrent, epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy, regardless of BRCA status;•New use of LYNPARZA tablets (2 tablets twice daily) as opposed to capsules (8 capsules twice daily);3•LYNPARZA tablets also now indicated (conversion from the current accelerated approval4) for the use in adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCA) advanced ovarian cancer, who have been treated with three or more prior lines of chemotherapy; patients for this indication are selected for therapy based on an FDA-approved companion diagnostic.Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, AstraZeneca said: “Physicians have almost three years of clinical experience with LYNPARZA on the market and we are now pleased to bring this important medicine, in a new tablet formulation, to a broader group of women. Today’s approvals validate more than 10 years of dedicated research behind LYNPARZA, the world’s first PARP inhibitor, which now provides oncologists with the greater flexibility for use in terms of treatment settings. It builds on our recently-announced collaboration with Merck, which aims to further increase the number of treatment options available to patients.”Richard Penson, MD, Clinical Director of Medical Gynecologic Oncology at Massachusetts General Hospital Cancer Center, Associate Professor of Medicine at Harvard Medical School, and the primary investigator in the SOLO-2 trial, said: “Today’s approval demonstrates that olaparib is an effective option for maintenance therapy for certain ovarian cancer patients, regardless of BRCA status. We welcome this news in the ovarian cancer community as more options are important to help us ensure that patients can find a treatment that is right for them.”Roger M. Perlmutter, President of Merck Research Laboratories, said: “We congratulate AstraZeneca on the approval of these new indications and the new dosage form andschedule for LYNPARZA, an important therapeutic advance for many patients with ovarian cancer. This is a significant first regulatory event in our collaboration with AstraZeneca. We look forward to working with AstraZeneca in our global collaboration to bring this medicine with its new indications to patients.”Two randomized trials supported the new approvals and the conversion of accelerated approval to full approval, which was originally based on a single-arm trial:1,3,4• SOLO-2 (n=295) confirmed the benefit of LYNPARZA in gBRCA-mutated patients, demonstrating a 70% reduced risk of disease progression or death (HR 0.30 [95% CI, 0.22-0.41], P<0.0001) and improved median progression-free survival (PFS) to 19.1 vs 5.5 months for placebo by investigator-assessed analysis.1• Study 19 (n=265) showed that LYNPARZA reduced the risk of disease progression or death by 65% and improved PFS compared with placebo in patients of any BRCA status (HR 0.35 [95% CI, 0.25-0.49], P<0.0001; median PFS of 8.4 months with LYNPARZA vs 4.8 months with placebo).1 Additionally, patients in Study 19, treated with LYNPARZA as a maintenance therapy, had a median overall survival (OS) of 29.8 months vs 27.8 months for placebo (HR 0.73 [95% CI, 0.55-0.95]).1Table 1. Summary of key efficacy results from randomized trials:1AnalysisReduction in the risk of disease progression or death (PFS)Reduction in the risk of death (OS)SOLO-2[gBRCAm]LYNPARZA70% (HR 0.30 [95% CI, 0.22-0.41], P<0.0001)Data not yet maturePlaceboStudy 19[PSR OC*]2LYNPARZA65% (HR 0.35 [95% CI, 0.25-0.49], P<0.0001)27% (HR 0.73 [95% CI, 0.55-0.95]Placebo*PSR = Platinum-sensitive recurrent ovarian cancerThe most common adverse reactions (≥20%) in clinical trials were anemia, nausea, fatigue (including asthenia), vomiting, nasopharyngitis/upper respiratory tract infection/influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, and decreased appetite, constipation. and stomatitis. Most common laboratory abnormalities (≥25%) were decrease in hemoglobin, increase in mean corpuscular volume, decrease in lymphocytes, decrease in leukocytes, decrease in absolute neutrophil count, increase in serum creatinine and decrease in platelets.The full data from the SOLO-2 trial can be found in the July 25, 2017 publication of The Lancet Oncology.5LYNPARZA was first approved under the FDA’s Accelerated Approval program in December 2014, as a capsule formulation, making it the first poly ADP-ribose polymerase (PARP) inhibitor approved.3,6 Since then, more than 3,000 advanced ovarian cancer patients have been treated with LYNPARZA capsules.7 LYNPARZA capsules are not indicated for maintenance therapy.IMPORTANT SAFETY INFORMATIONDOSING AND ADMINISTRATIONTo avoid substitution errors and overdose, do not substitute LYNPARZA tablets with LYNPARZA capsules on a milligram-to-milligram basis due to differences in the dosing and bioavailability of each formulation. Recommended tablet dose is 300 mg, taken orally twice daily, with or without food. Continue treatment until disease progression or unacceptable toxicity. For adverse reactions, consider dose interruption or dose reduction.WARNINGS AND PRECAUTIONSThere are no contraindications for LYNPARZA.Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some of these patients also had a history of previous cancer or bone marrow dysplasia.Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt treatment with LYNPARZA and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months after receiving the final dose.ADVERSE REACTIONS—Maintenance SettingMost common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), and decreased appetite (21%).Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).ADVERSE REACTIONS—Advanced gBRCAm ovarian cancerMost common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue (including asthenia) (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: decrease in hemoglobin (90%), increase in mean corpuscular volume (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).DRUG INTERACTIONSAnticancer Agents: Clinical studies of LYNPARZA in combination with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be co-administered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers when using LYNPARZA. If a moderate inducer cannot be avoided, be aware of a potential for decreased efficacy of LYNPARZA.USE IN SPECIFIC POPULATIONSPediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.Lactation: No data are available regarding the presence of olaparib in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.Hepatic Impairment: No adjustment to the starting dose is required in patients with mild hepatic impairment (Child-Pugh classification A). There are no data in patients with moderate or severe hepatic impairment.Renal Impairment: No adjustment to the starting dose is necessary in patients with mild renal impairment (CLcr 51-80 mL/min). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).About SOLO-2SOLO-2 was a Phase III, randomized, double-blind, multicenter trial designed to determine the efficacy of LYNPARZA tablets as a maintenance monotherapy compared with placebo, in patients with platinum-sensitive, relapsed or recurrent gBRCA-mutated ovarian, fallopian tube and primary peritoneal cancer.8 The trial, conducted in collaboration with the European Network for Gynaecological Oncological Trial Groups (ENGOT) and Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein (GINECO), randomized 295 patients with documented germline BRCA1 or BRCA2 mutations who had received at least two prior lines of platinum-based chemotherapy and were in complete or partial response.5,8 Eligible patients were randomized to receive either LYNPARZA tablets (300mg twice daily) or placebo twice daily.5About Study19Study 19 was a Phase II, randomized, double-blind, placebo-controlled, multicenter trial, which eva luated the efficacy and safety of LYNPARZA capsules compared with placebo in relapsed, high-grade serous ovarian cancer patients, involving 82 sites across 16 countries. Patients received olaparib maintenance monotherapy, at a dose of 400mg per day or matching placebo. Treatment continued until disease progression provided that toxicities were manageable.2AboutLYNPARZA® (olaparib)LYNPARZA was the first FDA-approved oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumor DNA damage response (DDR) pathway deficiencies to potentially kill cancer cells.6,9,10 Specifically, in vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death.1LYNPARZA is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DDR mechanisms in cancer cells.LYNPARZA tablets are currently being investigated in combinations in a range of tumor types, including breast, prostate, and pancreatic cancer.LYNPARZA capsules (400mg twice daily) will still be available through a limited specialty pharmacy network, for patients currently being treated for deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. LYNPARZA tablets and capsules are not the same.

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