部份中文阿法替尼处方资料（仅供参考） 药品名称：阿法替尼薄膜包衣片 英文名称：Afatinib 商品名称：Giotrif®[欧洲] Gilotrif®[美国] 原研厂家：Boehringer Ingelheim Pharma GmbH & Co. KG 上市国家：美国 作用机制 Afatinib与EGFR(ErbB1)，HER2 (ErbB2)，和HER4 ErbB4)的激酶结构域共价结合和不可逆地抑制酪氨酸激酶自身磷酸化，导致ErbB信号的下调。 Afatinib显示自身磷酸化的抑制作用和在体外表达野生型EGFR细胞株的增殖或表达选择性EGFR外显子19缺失突变或外显子21 L858R突变，包括在患者中在可到达的afatinib浓度时，至少暂时，某些有一种次发T790M突变。此外，在体外afatinib抑制过表达HER2细胞株的增殖。 在植入肿瘤或过表达野生型 EGFR或HER2或在一种EGFR L858R/T790M双突变体模型裸鼠中用afatinib治疗导致肿瘤生长的抑制。 适应证和用途 Gilotrif是一种激酶抑制剂适用为有转移非小细胞肺癌(NSCLC)患者一线治疗其肿瘤有当用FDA批准的测试检出的表皮生长因子受体(EGFR)外显子19缺失或外显子21(L858R)取代突变。 使用限制：尚未在肿瘤有其他EGFR突变患者中确定Gilotrif®的安全性和疗效。 剂量和给药方法 （1）推荐剂量：40mg口服，每天1次。 （2）指导患者在进餐前至少1小时或后2小时服用Gilotrif。 剂型和规格 片：40mg，30mg，和20mg 禁忌证 无 警告和注意事项 （1）腹泻：腹泻可能导致脱水和肾衰。对严重和对抗腹泻药物无反应延长腹泻不给GILOTRIF。 （2）大疱和剥脱性皮肤疾病：0.15%患者中生严重大疱，起泡，和去角质病变。对威胁生命的皮肤反应终止药物。对严重和延长皮肤反应不给GILOTRIF。 （3）间质性肺病(ILD)：在1.5%患者发生。对肺症状急性发作或恶化不给GILOTRIF。如被诊断ILD终止 GILOTRIF。 （4）肝毒性：在0.18%患者中发生致命性肝损伤。用定期肝检验监视。对肝检验严重或恶化不给或终止 GILOTRIF。 （5）角膜炎：在0.8%患者中发生。不给GILOTRIF对角膜炎评价。对确证溃疡性角膜炎不给或终止GILOTRIF。 （6）胚胎胎儿毒性：可致胎儿危害。劝告女性对胎儿潜在危害和使用高效避孕。 不良反应 最常见不良反应(≥20%)是腹泻，皮疹/痤疮样皮炎，口腔炎，甲沟炎，干皮肤，食欲减低，瘙痒。 P-gp抑制剂的共同给药可能增加afatinib暴露。如不能耐受每天减低GILOTRIF 10mg。慢性Pgp诱导剂口服的共同给药可能减低afatinib暴露。当耐受时每天增加Gilotrif 10mg。 在特殊人群中使用 哺乳母亲：终止药物或哺乳。 国内外上市情况 阿法替尼由勃林格殷格翰公司研制开发，2013年7月在美国以Gilotrif为商品名获得批准，2013年9月在欧盟以Giotrif为商品名获得批准上市。2014年5月在日本以Giotrif（ジオトリフ錠）为商品名获批上市。 美国：片剂20mg、30mg、40mg（2013.7.12）；Boehringer Ingelheim公司持有；商品名Gilotrif 欧盟：片剂20mg、30mg、40mg、50mg（2013.9.25）；Boehringer Ingelheim International GmbH公司持有；商品名Gilotrif 日本：片剂20mg、30mg、40mg（2014.5.7）；日本ベーリンガーインゲルハイム株式会社公司持有；商品名ジオトリフ錠 中国进口：片剂20mg、30mg、40mg、50mg（2017.2.21）；Boehringer Ingelheim International GmbH公司持有；商品名吉泰瑞 IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Diarrhea Diarrhea has resulted in dehydration with or without renal impairment; some of these cases were fatal. In the pivotal study, diarrhea occurred in 96% of patients treated with GILOTRIF (n=229), of which 15% was Grade 3 in severity and occurred within the first 6 weeks. Renal impairment as a consequence of diarrhea occurred in 6.1% of patients treated with GILOTRIF, out of which 3 (1.3%) were Grade 3. For patients who develop prolonged Grade 2 diarrhea lasting more than 48 hours or greater than or equal to Grade 3 diarrhea, withhold GILOTRIF until diarrhea resolves to Grade 1 or less, and resume GILOTRIF with appropriate dose reduction. Provide patients with an anti-diarrheal agent (e.g., loperamide) for self-administration at the onset of diarrhea and instruct patients to continue anti-diarrheal therapy until loose bowel movements cease for 12 hours. Bullous and Exfoliative Skin Disorders Grade 3 cutaneous reactions characterized by bullous, blistering, and exfoliating lesions occurred in 6 (0.15%) of the 3865 patients who received GILOTRIF across clinical trials. In the pivotal study, the overall incidence of cutaneous reactions consisting of rash, erythema, and acneiform rash was 90%, and the incidence of Grade 3 cutaneous reactions was 16%. In addition, the incidence of Grade 1-3 palmar-plantar erythrodysesthesia syndrome was 7%. Discontinue GILOTRIF in patients who develop life-threatening bullous, blistering, or exfoliating lesions. For patients who develop prolonged Grade 2 cutaneous adverse reactions lasting more than 7 days, intolerable Grade 2, or Grade 3 cutaneous reactions, withhold GILOTRIF until the adverse reaction resolves to Grade 1 or less, and resume GILOTRIF with appropriate dose reduction. Interstitial Lung Disease (ILD) ILD or ILD-like adverse reactions (e.g., lung infiltration, pneumonitis, acute respiratory distress syndrome, or alveolitis allergic) occurred in 1.5% of the 3865 patients who received GILOTRIF across clinical trials; of these, 0.4% were fatal. The incidence of ILD appeared to be higher in patients of Asian ethnicity (2.1%) as compared to non-Asians (1.2%). In the pivotal study, the incidence of Grade ≥3 ILD was 1.3% and resulted in death in 1% of GILOTRIF-treated patients. Withhold GILOTRIF during evaluation of patients with suspected ILD, and discontinue GILOTRIF in patients with confirmed ILD. Hepatic Toxicity In 3865 patients who received GILOTRIF across clinical trials, 10.1% had liver test abnormalities, of which 7 (0.18%) were fatal.  In the pivotal study, liver test abnormalities of any grade occurred in 17.5% of the patients treated with GILOTRIF. Obtain periodic liver testing in patients during treatment with GILOTRIF. Withhold GILOTRIF in patients who develop worsening of liver function. In patients who develop severe hepatic impairment while taking GILOTRIF, treatment should be discontinued. Keratitis Keratitis, characterized as acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, and/or red eye occurred in 0.8% of patients treated with GILOTRIF among 3865 patients across clinical trials. Keratitis was reported in 5 (2.2%) patients in the pivotal study, with Grade 3 in 1 (0.4%).  Withhold GILOTRIF during evaluation of patients with suspected keratitis, and if diagnosis of ulcerative keratitis is confirmed, treatment with GILOTRIF should be interrupted or discontinued. If keratitis is diagnosed, the benefits and risks of continuing treatment should be carefully considered. GILOTRIF should be used with caution in patients with a history of keratitis, ulcerative keratitis, or severe dry eye. Contact lens use is also a risk factor for keratitis and ulceration. Embryofetal Toxicity GILOTRIF is Pregnancy Category D. Based on its mechanism of action, GILOTRIF can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Advise females of reproductive potential to use highly effective contraception during treatment, and for at least 2 weeks after the last dose of GILOTRIF. Advise patients to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking GILOTRIF. ADVERSE REACTIONS In GILOTRIF-treated patients (n=229) the most common adverse reactions in the pivotal study (≥20% all grades & vs pemetrexed/cisplatin-treated patients (n=111)) were diarrhea (96% vs 23%), rash/dermatitis acneiform (90% vs 11%), stomatitis (71% vs 15%), paronychia (58% vs 0%), dry skin (31% vs 2%), decreased appetite (29% vs 55%), pruritus (21% vs 1%). Serious adverse reactions were reported in 29% of patients treated with GILOTRIF. The most frequent serious adverse reactions reported in patients treated with GILOTRIF were diarrhea (6.6%); vomiting (4.8%); and dyspnea, fatigue, and hypokalemia (1.7% each). Fatal adverse reactions in GILOTRIF-treated patients included pulmonary toxicity/ILD-like adverse reactions (1.3%), sepsis (0.43%), and pneumonia (0.43%). More GILOTRIF-treated patients (2.2%; n=5) experienced ventricular dysfunction (defined as diastolic dysfunction, left ventricular dysfunction, or ventricular dilation; all < Grade 3) compared to chemotherapy-treated patients (0.9%; n=1). DRUG INTERACTIONS Effect of P-glycoprotein (P-gp) Inhibitors and Inducers Concomitant taking of P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) with GILOTRIF can increase exposure to afatinib. Concomitant taking of P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital, and St. John’s wort) with GILOTRIF can decrease exposure to afatinib. USE IN SPECIFIC POPULATIONS Nursing Mothers It is not known whether afatinib is present in human milk.  Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from GILOTRIF, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Renal Impairment GILOTRIF has not been studied in patients with severely impaired renal function. Closely monitor patients with moderate (CLcr 30-59 mL/min) to severe (CLcr <30 mL/min) renal impairment and adjust GILOTRIF dose if not tolerated. Hepatic Impairment GILOTRIF has not been studied in patients with severe (Child Pugh C) hepatic impairment. Closely monitor patients with severe hepatic impairment and adjust GILOTRIF dose if not tolerated. GF PROF ISI SEPT 2013 Please click here to view the full Prescribing Information, including Patient Information Gilotrif(afatinib)为肺癌患者带来希望 2013年7月12日美国食品和药品监督管理局(FDA)批准Gilotrif(afatinib)为治疗晚期(转移)非小细胞肺癌(NSCLC)的一种药品。 按照美国国家癌症研究所，2013年估计有228,190美国人被诊断有肺癌，而159,480死于该病。约85%肺癌是NSCLC，使之为肺癌最常见类型。约10%的NSCLC中存在EGFR基因突变，这些基因突变多数表现为EGFR外显子19缺失或外显子21 L858R取代。 Gilotrif是一种酪氨酸激酶抑制剂，可以阻断促进癌细胞发展的蛋白。意图在于治疗肿瘤表达EGFR外显子19缺失或外显子21 L858R取代基因突变患者。Gilotrif正在被批准与therascreen EGFR RGQ PCR Kit协同诊断，从而有助于确定患者的肺癌细胞是否表达EGFR突变。 美国FDA药物评价和研究中心血液学和肿瘤学室主任Richard Pazdur，M.D.说：“今天的批准可能导致靶向治疗的发展，”“Gilotrif是今年被批准治疗肿瘤有EGFR外显子19缺失或外显子21 L858R取代突变，并且未得到有效的转移NSCLC患者的第二个药物。” 在2013年5月，FDA批准Tarceva(厄洛替尼[erlotinib])对NSCLC患者的一线治疗。在Tarceva的新适应证批准同时，批准与cobas EGFR突变测试，一种协同诊断确定患者有EGFR基因突变肿瘤。 美国FDA装置和放射卫生中心，体外诊断和放射卫生室主任Alberto Gutierrez，Ph.D.说：“协同诊断测试和药物的批准在肿瘤学是重要发展，因为它们帮助我们对需要它们的患者进行安全和有效治疗。” FDA批准therascreen EGFR RGQ PCR是根据来自使用支持Gilotrif的批准的临床研究数据。在一项有转移NSCLC，肿瘤有EGFR突变的临床研究中，345例参加者被随机赋予接受Gilotrif或直至6个疗程的化疗药物培美曲塞[pemetrexed]和顺铂[cisplatin]。从而确定Gilotrif的安全性和有效性。 参加者接受Gilotrif有延迟肿瘤生长(无进展生存)是4.2个月晚于接受化疗患者。总生存无统计意义差别。 Gilotrif的常见副作用包括腹泻，皮疹相似于痤疮，干皮肤，瘙痒，口腔炎症，甲沟炎，食欲减低，体重减轻，膀胱炎，鼻出血，流鼻涕，发热，眼炎和低钾血症。严重副作用包括腹泻可能导致肾衰和严重脱水，严重皮疹，肺炎和肝脏毒性。 FDA在优先审评计划下审评Gilotrif，它提供一种加快评审可能提供安全和有效治疗药物当没有另外已有满意治疗时，或比已上市产品提供显著改进时。 Gilotrif由Boehringer Ingelheim Pharmaceuticals，Inc公司上市。Therascreen EGFR RGQ PCR药盒由总部在英国的QIAGEN Manchester Ltd制造，Cobas EGFR突变测试由加州普莱森Roche Molecular Systems制造，而Tarceva由加州的Genentech 和纽约Farmingdale的OSI Pharmaceuticals共同上市。 ------------------------------------------------------------- 产地国家：美国 原产地英文商品名: Gilotrif 20mg/Tablet 30Tablets/ 原产地英文药品名: afatinib 中文参考商品译名: Gilotrif 20mg毫克/片 30片 中文参考药品译名: 阿法替尼 生产厂家中文参考译名: 勃林格殷格翰制药公司 生产厂家英文名: Boehringer Ingelheim Pharmaceuticals Inc. ------------------------------------------------------------- 产地国家：美国 原产地英文商品名: Gilotrif 30mg/Tablet 30Tablets/ 原产地英文药品名: afatinib 中文参考商品译名: Gilotrif 30mg毫克/片 30片 中文参考药品译名: 阿法替尼 生产厂家中文参考译名: 勃林格殷格翰制药公司 生产厂家英文名: Boehringer Ingelheim Pharmaceuticals Inc. ------------------------------------------------------------- 产地国家：美国 原产地英文商品名: Gilotrif 40mg/Tablet 30Tablets/ 原产地英文药品名: afatinib 中文参考商品译名: Gilotrif 40mg毫克/片 30片 中文参考药品译名: 阿法替尼 生产厂家中文参考译名: 勃林格殷格翰制药公司 生产厂家英文名: Boehringer Ingelheim Pharmaceuticals Inc.