英文药名：AFINITOR tablets/dispersible tablets(Everolimus) 中文药名：依维莫司片/分散片 生产厂家：诺华制药 アフィニトール錠2.5mg／アフィニトール錠5mg アフィニトール分散錠2mg／アフィニトール分散錠3mg 治疗类别名称 抗肿瘤药物（mTOR抑制剂） 商標名 AFINITOR dispersible tablets AFINITOR tablets 構造式 一般名 エベロリムス（Everolimus） 化学名 （1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R）-1,18-Dihydroxy-12-｛（1R）-2-［（1S,3R,4R）-4-（2-hydroxyethoxy）-3-methoxycyclohexyl］-1-methylethyl｝-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo［30.3.1.04,9］hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentaone 分子式 C53H83NO14 分子量 958.22 性状 白色至浅黄色粉末，易溶于乙醇（99.5），并且几乎不溶于水。 批准条件 激进无法切除或转移性肾细胞癌 肾细胞癌的诊断，用的是处方药，只有通过医生谁是熟悉的化疗使用，待原药店谁是医生，医疗机构和管理药剂师可以充分控制也是关于该药物等的风险只用，拿在生产销售的必要措施。 胰腺神经内分泌肿瘤 1.制造和销售后，直到按一定许多情况下，数据集成，通过实现对一切案件的使用效果调查，以及了解这种药物的患者使用的背景信息，这种药物数据早来收集安全性和有效性，采取必要的措施，正确使用此药。 2.诊断胰腺神经内分泌肿瘤，与沿是处方及仅由医师谁熟悉化疗，在原来的药房谁是医生，医疗机构和管理药剂师可充分控制也有关此代理人的风险中使用，并且仅等所用。 不能手术或复发性乳腺癌 乳腺癌的诊断，与沿是处方及仅由医师谁熟悉化疗使用，也可以在原始的药房谁是医生，医疗机构和管理药剂师可充分控制也有关此代理人的风险，或类似的，制造仅用于销售在采取必要的措施。 与结节性硬化症和结节性硬化症相关的肾错构瘤相关的室管膜下巨细胞星形细胞瘤。 结节性硬化症的诊断，用的是处方药，只有通过医生谁是熟悉的用于治疗，将在原来的药店谁是医生，医疗机构和管理药剂师可以充分控制也是关于该药物等的风险只用。 适应病症 1. 激进无法切除或转移性肾细胞癌 2. 胰腺神经内分泌肿瘤 3. 不能手术或复发性乳腺癌 4. 结节性硬化症相关的肾错构瘤 5. 结节性硬化症相关的室管膜下巨细胞星形细胞瘤 用法用量 肾细胞癌，胰腺神经内分泌肿瘤，肾血管平滑肌脂肪瘤结节性硬化症相关联的情况下 成年人口服，每日一次，每次为10mg。此外，根据该状态的患者用药。 在不能手术或复发性乳腺癌的情况下 成年人口服，每日一次，每次为10mg。此外，根据该状态的患者用药。 在室管膜下巨细胞星形细胞瘤结节性硬化症相关的情况下， 每天一次，每次为3.0mg/m 2至口服给药。所述剂量可根据患者的状态和波谷浓度进行调整。 药效药理 1.抗肿瘤作用 在体外试验中，依维莫司抑制人和啮齿类动物肿瘤衍生的细胞系的生长。另外，在体内研究中，依维莫司抑制人肿瘤细胞系的小鼠异种移植物，同基因肿瘤植入小鼠和同基因肿瘤移植大鼠的肿瘤生长。 2.血管生成抑制效应 在体外研究，依维莫司由血管内皮生长因子（VEGF），碱性成纤维细胞生长因子的人脐静脉内皮细胞的抑制增殖。此外，依维莫司抑制肿瘤细胞血管内皮生长因子的生产。在体内试验，依维莫司，其中皮下植入到小鼠含有VEGF-室的抑制血管生成。在原位移植小鼠在B16/BL6黑色素瘤细胞，依维莫司减少植入部位及转移部位的肿瘤血管密度。 3. 对TSC基因缺陷小鼠的行动 依维莫司，其中结节性硬化症（TSC），其被认为是引起基因为结节性硬化症，延长在神经元细胞中的TSC1基因缺陷的小鼠的存活天数，减少的磷酸化S6在大脑基因这是。此外，依维莫司抑制在TSC2基因杂缺陷型小鼠中观察肾肿瘤的形成。 4. 作用机序 依维莫司，FKBP（FK506结合蛋白）是一种细胞内亲免。的依维莫司和FKBP12复杂被认为选择性地抑制mTOR的是丝氨酸-苏氨酸激酶。mTOR的通过磷酸p70S6激酶和4E-BP1，细胞生长，所涉及的增殖和存活调节蛋白质的合成。 在荷瘤小鼠和肿瘤携带鼠的肿瘤接受依维莫司是抑制p70S6激酶，在接受依维莫司荷瘤大鼠的肿瘤4E-BP1磷酸化被抑制。 包装规格 1.分散片 2毫克 30片（双面铝PTP） 3毫克30片（双面铝PTP） 2.片剂 2.5mg  30片（双面铝PTP） 5mg    30（双面铝PTP） 制造和销售 诺华制药有限公司 注：以上中文资料仅供参考，使用以原处方为准！ 1）http://www.info.pmda.go.jp/go/pack/4291023F1020_1_19/ 2）http://www.info.pmda.go.jp/go/pack/4291023X1026_1_07/ Afinitor (Everolimus Tablets) Advanced HR+, HER2-Negative Breast Cancer AFINITOR is indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane after failure of treatment with letrozole or anastrozole. Advanced Neuroendocrine Tumors of Pancreatic Origin AFINITOR is indicated for the treatment of adults with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced, or metastatic disease. AFINITOR is not indicated for the treatment of patients with functional carcinoid tumors. Progressive, Well-Differentiated, Nonfunctional Gl and Lung Neuroendocrine Tumor AFINITOR is indicated for the treatment of adults with progressive, well-differentiated, nonfunctional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin with unresectable, locally advanced, or metastatic disease. AFINITOR is not indicated for the treatment of patients with functional carcinoid tumors. Advanced Renal Cell Carcinoma AFINITOR is indicated for the treatment of adults with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib. Renal Angiomyolipoma With Tuberous Sclerosis Complex AFINITOR is indicated for the treatment of adults with renal angiomyolipoma (AML) and tuberous sclerosis complex (TSC) not requiring immediate surgery. SEGA With Tuberous Sclerosis Complex AFINITOR Tablets and AFINITOR DISPERZ™ (everolimus tablets for oral suspension) are indicated in pediatric and adult patients with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected. Important Safety Information AFINITOR is contraindicated in patients with hypersensitivity to everolimus, to other rapamycin derivatives, or to any of the excipients. Noninfectious Pneumonitis: Noninfectious pneumonitis was reported in up to 19% of patients treated with AFINITOR. The incidence of Common Terminology Criteria (CTC) grade 3 and 4 noninfectious pneumonitis was up to 4.0% and up to 0.2%, respectively. Fatal outcomes have been observed. Monitor for clinical symptoms or radiological changes. Opportunistic infections such as Pneumocystis jiroveci pnuemonia (PJP) should be considered in the differential diagnosis. Manage noninfectious pneumonitis by dose interruption until symptoms resolve, follow with a dose reduction, and consider the use of corticosteroids. Discontinue AFINITOR if toxicity recurs at grade 3 or for grade 4 cases. For patients who require use of corticosteroids, prophylaxis for PJP may be considered. The development of pneumonitis has been reported even at a reduced dose. Infections: AFINITOR has immunosuppressive properties and may predispose patients to bacterial, fungal, viral, or protozoal infections (including those with opportunistic pathogens). Localized and systemic infections, including pneumonia, mycobacterial infections, other bacterial infections; invasive fungal infections such as aspergillosis, candidiasis, or PJP; and viral infections, including reactivation of hepatitis B virus, have occurred. Some of these infections have been severe (eg, leading to sepsis, respiratory failure, or hepatic failure) or fatal. Physicians and patients should be aware of the increased risk of infection with AFINITOR. Treatment of preexisting invasive fungal infections should be completed prior to starting treatment with AFINITOR. Be vigilant for signs and symptoms of infection and institute appropriate treatment promptly; interruption or discontinuation of AFINITOR should be considered. Discontinue AFINITOR if invasive systemic fungal infection is diagnosed and institute appropriate antifungal treatment. PJP has been reported in patients who received everolimus, sometimes with a fatal outcome. This may be associated with concomitant use of corticosteroids or other immunosuppressive agents; consider prophylaxis for PJP when concomitant use of these agents is required. Angioedema With Concomitant Use of Angiotensin-Converting Enzyme (ACE) Inhibitors: Patients taking concomitant ACE inhibitor therapy may be at increased risk for angioedema (eg, swelling of the airways or tongue, with or without respiratory impairment). In a pooled analysis, the incidence of angioedema in patients taking everolimus with an ACE inhibitor was 6.8% compared to 1.3% in the control arm with an ACE inhibitor. Oral Ulceration: Mouth ulcers, stomatitis, and oral mucositis have occurred in patients treated with AFINITOR at an incidence ranging from 44% to 78% across the clinical trial experience. Grade 3/4 stomatitis was reported in 4% to 9% of patients. In such cases, topical treatments are recommended, but alcohol-, hydrogen peroxide-, iodine-, or thyme-containing mouthwashes should be avoided. Antifungal agents should not be used unless fungal infection has been diagnosed. Renal Failure: Cases of renal failure (including acute renal failure), some with a fatal outcome, have been observed in patients treated with AFINITOR. Impaired Wound Healing: Everolimus delays wound healing and increases the occurrence of wound-related complications like wound dehiscence, wound infection, incisional hernia, lymphocele, and seroma. These wound-related complications may require surgical intervention. Exercise caution with the use of AFINITOR in the perisurgical period. Geriatric Patients: In the randomized advanced hormone receptor-positive, HER2-negative breast cancer study, the incidence of deaths due to any cause within 28 days of the last AFINITOR dose was 6% in patients ≥65 years of age compared with 2% in patients <65 years of age. Adverse reactions leading to permanent discontinuation occurred in 33% of patients ≥65 years of age compared with 17% in patients <65 years of age. Careful monitoring and appropriate dose adjustments for adverse reactions are recommended. Laboratory Tests and Monitoring: Elevations of serum creatinine and proteinuria have been reported. Renal function (including measurement of blood urea nitrogen, urinary protein, or serum creatinine) should be evaluated prior to treatment and periodically thereafter, particularly in patients who have additional risk factors that may further impair renal function. Hyperglycemia, hyperlipidemia, and hypertriglyceridemia have been reported. Blood glucose and lipids should be evaluated prior to treatment and periodically thereafter. More frequent monitoring is recommended when AFINITOR is coadministered with other drugs that may induce hyperglycemia. Management with appropriate medical therapy is recommended. When possible, optimal glucose and lipid control should be achieved before starting a patient on AFINITOR. Reductions in hemoglobin, lymphocytes, neutrophils, and platelets have been reported. Monitoring of complete blood count is recommended prior to treatment and periodically thereafter. Drug-Drug Interactions: Avoid coadministration with strong CYP3A4/PgP inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole). Use caution and reduce the AFINITOR dose to 2.5 mg daily if coadministration with a moderate CYP3A4/PgP inhibitor is required (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem). Avoid coadministration with strong CYP3A4/PgP inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital); however, if coadministration is required, consider doubling the daily dose of AFINITOR using increments of 5 mg or less. Hepatic Impairment: Exposure to everolimus was increased in patients with hepatic impairment. For patients with severe hepatic impairment (Child-Pugh class C), AFINITOR may be used at a reduced dose if the desired benefit outweighs the risk. For patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment, a dose reduction is recommended. Vaccinations: The use of live vaccines and close contact with those who have received live vaccines should be avoided during treatment with AFINITOR. Embryo-Fetal Toxicity: Fetal harm can occur if AFINITOR is administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise female patients of reproductive potential of the potential risk to a fetus and to use effective contraception while using AFINITOR and for 8 weeks after ending treatment. Adverse Reactions in Advanced Breast Cancer: The most common adverse reactions (incidence ≥30%) were stomatitis (67%), infections (50%), rash (39%), fatigue (36%), diarrhea (33%), and decreased appetite (30%). The most common grade 3/4 adverse reactions (incidence ≥2%) were stomatitis (8%), infections (5%), hyperglycemia (5%), fatigue (4%), dyspnea (4%), pneumonitis (4%), and diarrhea (2%). Laboratory Abnormalities in Advanced Breast Cancer: The most common laboratory abnormalities (incidence ≥50%) were hypercholesterolemia (70%), hyperglycemia (69%), increased aspartate transaminase (AST, 69%), anemia (68%), leukopenia (58%), thrombocytopenia (54%), lymphopenia (54%), increased alanine transaminase (ALT, 51%), and hypertriglyceridemia (50%). The most common grade 3/4 laboratory abnormalities (incidence ≥3%) were lymphopenia (12%), hyperglycemia (9%), anemia (7%), decreased potassium (4%), increased AST (4%), increased ALT (4%), and thrombocytopenia (3%). Adverse Reactions in Advanced PNET: The most common adverse reactions (incidence ≥30%) were stomatitis (70%), rash (59%), diarrhea (50%), fatigue (45%), edema (39%), abdominal pain (36%), nausea (32%), fever (31%), headache (30%), and decreased appetite (30%). The most common grade 3/4 adverse reactions (incidence ≥5%) were stomatitis (7%) and diarrhea (5.5%). Deaths primarily due to adverse events during the double-blind treatment phase occurred in 7 patients taking AFINITOR. Laboratory Abnormalities in Advanced PNET: The most common laboratory abnormalities (incidence ≥50%, all grades) were decreased hemoglobin (86%) and bicarbonate (56%); increased fasting glucose (75%), alkaline phosphatase (74%), cholesterol (66%), and aspartate transaminase (56%). The most common grade 3/4 laboratory abnormalities (incidence ≥5%) were decreased hemoglobin (15%), lymphocytes (16%), and phosphate (10%), and increased glucose (17%) and alkaline phosphatase (8%). Adverse Reactions in Progressive, Well-Differentiated, Nonfunctional GI and Lung NET: The most common adverse reactions (incidence ≥30%) were stomatitis (63%), infections (58%), diarrhea (41%), peripheral edema (39%), fatigue (37%), and rash (30%). The most common grade 3/4 adverse reactions (incidence ≥5%) were infections (11%), stomatitis (9%), diarrhea (9%), fatigue (5%), and hyperglycemia (5%). Laboratory Abnormalities in Progressive, Well-Differentiated, Nonfunctional GI and Lung NET: The most common laboratory abnormalities (incidence ≥50%, all grades) were anemia (81%), hypercholesterolemia (71%), lymphopenia (66%), elevated aspartate transaminase (57%), and hyperglycemia (55%). The most common grade 3/4 laboratory abnormalities (incidence ≥5%) were lymphopenia (17%), hyperglycemia (6%), elevated alanine transaminase (6%), hypokalemia (6%), and anemia (5%). Adverse Reactions in Advanced RCC: The most common adverse reactions (incidence ≥30%) were stomatitis (44%), infections (37%), asthenia (33%), fatigue (31%), cough (30%), and diarrhea (30%). The most common grade 3/4 adverse reactions (incidence ≥5%) were infections (10%), dyspnea (7%), stomatitis (5%), and fatigue (5%). Laboratory Abnormalities in Advanced RCC: The most common laboratory abnormalities (incidence ≥50%, all grades) were: decreased hemoglobin (92%) and lymphocytes (51%); and increased cholesterol (77%), triglycerides (73%), glucose (57%), and creatinine (50%). The most common grade 3/4 laboratory abnormalities (incidence ≥5%) were decreased hemoglobin (13%), lymphocytes (18%), and phosphate (6%), and increased glucose (16%). Adverse Reactions in Renal AML-TSC: The most common adverse reaction (incidence ≥30%) was stomatitis (78%). The most common grade 3/4 adverse reactions (incidence ≥2%) were stomatitis and amenorrhea. Updated safety information from 112 patients treated with AFINITOR for a median duration of 3.9 years identified the following additional adverse reactions: urinary tract infection (31%), abdominal pain (16%), pruritus (12%), gastroenteritis (12%), myalgia (11%), and pneumonia (10%). Laboratory Abnormalities in Renal AML-TSC: The most common laboratory abnormalities (incidence ≥50%) were hypercholesterolemia (85%), hypertriglyceridemia (52%), and anemia (61%). The most common grade 3/4 laboratory abnormality (incidence ≥2%) was hypophosphatemia (5%). Updated safety information from 112 patients treated with AFINITOR for a median duration of 3.9 years identified the following additional key laboratory abnormalities: increased partial thromboplastin time (63%), increased prothrombin time (40%), decreased fibrinogen (38%), and proteinuria (18%). Adverse Reactions in SEGA-TSC: The most common adverse reactions (incidence ≥30%, all grades) in the phase 3 study were stomatitis (62%) and respiratory tract infection (31%). The most common grade 3/4 adverse reactions (incidence ≥2%) in the phase 3 study were stomatitis, pyrexia, pneumonia, gastroenteritis, aggression, agitation, and amenorrhea. Updated safety information from 111 patients treated with AFINITOR for a median duration of 47 months identified the following additional notable adverse reactions: decreased appetite (14%), hypertension (11%), urinary tract infection (9%), cellulitis (6%), abdominal pain (5%), and decreased weight (5%). Laboratory Abnormalities in SEGA-TSC: The most common key laboratory abnormalities (incidence ≥50%, all grades) in the phase 3 study were hypercholesterolemia (81%) and elevated partial thromboplastin time (72%). The most common grade 3/4 laboratory abnormality (incidence ≥3%) in the phase 3 study was neutropenia (9%). Updated safety information from 111 patients treated with AFINITOR for a median duration of 47 months identified the following additional key laboratory abnormalities: hyperglycemia (13%), decreased fibrinogen (8%), elevated creatinine (5%), and azospermia (1%).