近日，抗肿瘤激酶抑制剂Votrient(pazopanib)帕唑帕尼片获美国FDA及欧盟批准上市治疗晚期肾细胞癌、软组织肉瘤、晚期卵巢癌的有效药物。 2017年5月27日美国FDA修改说明书；公司：Novartis和葛兰素史克GlaxoSmithKline VOTRIENT(帕唑帕尼[pazopanib])片，口服使用 初步批准日期:2009年 警告:肝毒性 请参阅完整的处方信息的完整框警告。 在临床试验中观察到严重和致命的肝毒性。监测肝功能并按建议中断、减少或停止给药[参见警告和注意事项]。 最近的重大变化 警告和预防措施,Embryo-Fetal毒性:5/2017 作用机制 Pazopanib multi-tyrosine激酶抑制剂的血管内皮生长因子受体(VEGFR)1,VEGFR-2,VEGFR-3,血小板源生长因子受体(PDGFR)-α-β,纤维母细胞生长factorreceptor(FGFR)1和3,细胞因子受体(装备)、白介素2 receptor-induciblet细胞激酶(Itk)lymphocyte-specific蛋白质酪氨酸激酶(Lck)和跨膜糖蛋白受体酪氨酸激酶(cfm)。在体外，帕唑帕尼抑制配体诱导的VEGFR-2、Kit和pdgfr受体的自磷酸化。在体内，pazopanib抑制了vegf诱导的小鼠肺内VEGFR-2磷酸化，在小鼠模型中抑制血管生成，在小鼠体内抑制了一些人肿瘤异种移植物的生长。 适应症和用法 VOTRIENT是一种激酶抑制剂，用于治疗: 晚期肾细胞癌。 接受过化疗的晚期软组织肉瘤。 使用限制:VOTRIENT治疗脂肪性软组织肉瘤或胃肠道间质瘤的疗效尚未见报道被证实。 剂量和管理 每日口服800毫克，不含食物(至少饭前1小时或饭后2小时)。基线中度肝损害-每日口服200毫克。严重肝损害患者不推荐使用。 剂型和强度 200毫克片剂 禁忌症 没有 警告和预防措施 观察血清转氨酶和胆红素水平升高。发生了严重而致命的肝毒性。在治疗开始前和治疗期间定期测量肝脏的化学成分。观察到延长的QT间隔和点扭转。在发生QT间期延长风险较高的患者中慎用。监测心电图(ECGs)和电解质应该被考虑。 心脏功能障碍，如充血性心力衰竭和左室射血分数降低(LVEF)已经发生。监测血压，及时处理高血压。对于有心脏功能障碍风险的患者，推荐基线和定期评估ofLVEF。 已经报告了致命的出血事件。VOTRIENT在过去6个月里没有在有咯血、脑出血或临床意义重大的消化道出血史的患者中进行研究，不应该在这些患者中使用。已经观察到动脉血栓栓塞事件，可能是致命的。在发生这些事件的风险增加的患者中要谨慎使用。 静脉血栓栓塞事件(VTE)已被观察到，包括fatalpulmonary emboli (PE)。监测VTE和PE的体征和症状。 血栓性微血管病(TMA)包括血栓性血小板减少性紫癜(TTP)和溶血性尿毒症综合征(HUS)。如果TMA发生，永久停止VOTRIENT。 发生胃肠穿孔或瘘。致命的穿孔事件发生。在有胃肠疾病危险的患者中慎用穿孔或瘘管。间质性肺疾病(ILD)/肺炎已被观察到，可能是致命的。停止VOTRIENT在病人发展固体或肺炎。可逆性后部白质脑病综合征(RPLS)已被观察到，可能是致命的。永久停止住院VOTRIENT患者发展RPLS。高血压包括高血压危象已被观察到。在使用VOTRIENT前应控制好血压。在服用VOTRIENT后一周内监测血压，此后经常监测血压。 在进行外科手术的病人中，建议中断VOTRIENT疗法。 可能发生甲状腺功能减退。建议监测甲状腺功能测试。 蛋白尿:监测尿蛋白。中断治疗24小时尿蛋白大于或等于3克，并停止重复发作，尽管剂量减少。 感染:严重感染(伴或不伴中性粒细胞减少症)，有些会导致死亡。监测体征和症状，及时治疗活动性感染。中断或中断VOTRIENT。 动物研究表明，VOTRIENT在出生后早期发育过程中会严重影响胚胎的生长发育和成熟。儿童患者的安全性和有效性尚未得到证实。 胚胎-胎儿毒性:VOTRIENT可对孕妇造成胎儿伤害。建议女性注意生育的潜在风险，并建议女性和男性使用有效的避孕措施。 不良反应 晚期肾细胞癌(大于等于20%)患者最常见的不良反应是腹泻、高血压、发色改变(脱色)、恶心、厌食、呕吐。 晚期软组织肉瘤(大于或等于20%)患者最常见的不良反应是疲劳、腹泻、恶心、体重减轻、高血压、食欲下降、发色改变、呕吐、肿瘤疼痛、味觉障碍、头痛、肌肉骨骼疼痛、肌痛、胃肠道疼痛和呼吸困难。 若要报告可疑的不良反应，请联系NovartisPharmaceuticals Corporation(电话1-888-669-6682)或FDA(电话1-800-FDA-1088)或www.fda.gov/medwatch。 药物的相互作用 CYP3A4抑制剂:避免使用强CYP3A4抑制剂。如果需要联合用药，将VOTRIENT的剂量降低到400毫克。 CYP3A4诱导物:考虑一种具有noor最小酶诱导潜能或避免VOTRIENT的替代药物。 CYP底物:不建议同时使用经CYP3A4、CYP2D6、orCYP2C8代谢的治疗窗狭窄的VOTRIENT。 同时使用VOTRIENT和辛伐他汀会增加丙氨酸氨基转移酶(ALT)升高的风险，应谨慎和密切监测。 提高胃pH值的药物:避免同时使用VOTRIENT和提高胃pH值的药物。考虑用短效抗酸剂代替质子泵抑制剂(PPIs)和H2受体拮抗剂。分离盐酸和帕唑帕尼，给药数小时。 在特定人群中使用 哺乳期:建议不要母乳喂养。 包装提供/储存和处理 这种200毫克的VOTRIENT药片胶囊状，呈灰色，涂有一层GS JT的薄膜 侧和可在: 每瓶120片:NDC 0078-0670-66 Store室温在20C和25之间C(68F 77F);远足允许15C 30C(59F到86年F)[see USP Controlled Room Temperature]. Votrient (Pazopanib Tablets) VOTRIENT(pazopanib)tablets is a prescription medicine used to treat people with advanced renal cell cancer (RCC). VOTRIENT is a prescription medicine used to treat people with advanced soft tissue sarcoma (STS) who have received chemotherapy in the past. It is not known if VOTRIENT is effective in treating certain soft tissue sarcomas or certain gastrointestinal tumors. It is not known if VOTRIENT is safe and effective in children under 18 years of age. Important Safety Information, including Boxed WARNING Before taking VOTRIENT, tell your health care provider if you have or had liver problems. Some people may develop liver damage while taking VOTRIENT. VOTRIENT can cause serious liver problems, including death. Your health care provider will do blood tests to check your liver before you start and while you take VOTRIENT. Tell your health care provider right away if you have yellow eyes or skin, dark urine, tiredness, nausea or vomiting, loss of appetite, pain in the right upper side of your stomach area, or if you bruise easily. Your health care provider may need to prescribe a lower dose of VOTRIENT for you or tell you to stop taking VOTRIENT if you develop liver problems during treatment. VOTRIENT may cause irregular or fast heartbeat or fainting. VOTRIENT may cause heart failure, a condition where your heart does not pump as well as it should and which may result in shortness of breath. Heart attack and stroke can happen with VOTRIENT and may cause death. Tell your health care provider if you have heart problems. Call your health care provider right away if you have chest pain or pressure, pain in your arms, back, neck, or jaw, shortness of breath, numbness or weakness on one side of your body, trouble talking, headache, or dizziness. VOTRIENT may cause blood clots, which may form in a vein, especially in your legs. Pieces of a blood clot may travel to your lungs. This may be life threatening and cause death. Call your health care provider right away if you have new chest pain, trouble breathing or sudden shortness of breath, leg pain, and swelling of the arms and hands, or legs and feet, a cool or pale arm or leg. Thrombotic microangiopathy (TMA), including thrombotic thrombocytopenia purpura and hemolytic uremic syndrome, is a condition involving blood clots that can happen while taking VOTRIENT. TMA is accompanied by a decrease in red blood cells and cells that are involved in clotting. TMA may harm organs such as the brain and kidneys. VOTRIENT may cause bleeding problems, which may be severe and cause death. Tell your health care provider before taking VOTRIENT if you have a history of abnormal bleeding. If you experience unusual bleeding, bruising, or wounds that do not heal, call your health care provider right away. VOTRIENT may cause a tear (called a perforation) in the stomach or intestinal wall. Fatal perforations have occurred. VOTRIENT may also cause an abnormal connection between 2 parts of your gastrointestinal tract (called a fistula). Call your health care provider if you experience pain or swelling in the stomach area, vomiting blood, or black sticky stools. VOTRIENT may cause lung problems that may lead to death. Tell your health care provider right away if you develop a cough that will not go away or have shortness of breath. Reversible posterior leukoencephalopathy syndrome is a condition that can happen while taking VOTRIENT that may cause death. Symptoms may include headaches, seizures, lack of energy, confusion, high blood pressure, loss of speech, blindness or changes in vision, and problems thinking. High blood pressure can happen with VOTRIENT, including a sudden and severe rise in blood pressure, which may be life threatening. These blood pressure increases usually happen in the first several months of treatment. Blood pressure should be well controlled before starting VOTRIENT. Your health care provider should test your blood pressure within 1 week of starting treatment with VOTRIENT and should check it often during treatment. Get medical help right away if you have symptoms of a severe increase in blood pressure, such as severe chest pain, severe headache, blurred vision, confusion, nausea and vomiting, severe anxiety, shortness of breath, or seizures, or if you pass out (become unconscious). VOTRIENT may cause thyroid problems. Your health care provider should test your thyroid function during treatment with VOTRIENT. VOTRIENT may affect wound healing. Tell your doctor if you had recent surgery (within the last 7 days) or are going to have surgery. VOTRIENT may cause you to have too much protein in your urine. Your health care provider will check you for this problem. If there is too much protein in your urine, your health care provider may tell you to stop taking VOTRIENT. Serious infections can happen with VOTRIENT and can cause death. Call your health care provider if you experience fever; cold symptoms, such as runny nose or a sore throat that does not go away; flu symptoms, such as cough, feeling tired, and body aches; pain when urinating; or cuts, scrapes, or wounds that are red, warm, swollen, or painful. When used in combination with some other anticancer therapies, VOTRIENT has caused increased toxicity and even death. Tell your health care provider about all of the medicines you are taking, including other anticancer therapies. FEMALES OF REPRODUCTIVE/CHILDBEARING POTENTIAL. VOTRIENT can harm your unborn baby (cause birth defects or potential loss of pregnancy). You should not become pregnant while you are taking VOTRIENT. You should use effective birth control during treatment with VOTRIENT and for at least 2 weeks after your final dose of VOTRIENT. Talk to your health care provider about the types of birth control that may be right for you during this time. MALES OF REPRODUCTIVE POTENTIAL. Talk to your doctor if you are a male, even if you have had a vasectomy, and you are with a sexual partner who is pregnant, thinks that she may be pregnant, or who could become pregnant (including those who use other forms of birth control). You should use condoms during sexual intercourse during treatment with VOTRIENT and for at least 2 weeks after your last dose with VOTRIENT. BREASTFEEDING. It is not known if VOTRIENT passes into your breast milk. Do not breastfeed during treatment with VOTRIENT and for 2 weeks after the final dose. A collapsed lung can happen with VOTRIENT (called pneumothorax). This may cause shortness of breath. Call your health care provider right away if you experience shortness of breath. The most common side effects in people who take VOTRIENT include: Diarrhea High blood pressure Change in hair color Nausea or vomiting Loss of appetite Other common side effects in people with advanced soft tissue sarcoma who take VOTRIENT include: Feeling tired Decreased weight Tumor, muscle, or bone pain Stomach pain Headache Taste changes Trouble breathing Change in skin color Tell your health care provider right away if you have any side effects. VOTRIENT may affect the way other medicines work and other medicines may affect how VOTRIENT works. Tell your health care provider about all the medicines you take, including prescription and nonprescription medicines, and herbal and dietary supplements. Do not eat grapefruit or drink grapefruit juice during treatment with VOTRIENT because it may affect how VOTRIENT works. https://www.us.votrient.com/ https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/votrient.pdf