CAPRELSA (Vandetanib tabs)-针对治疗不能切除的晚期或转移性甲状腺髓样癌
商品名：Caprelsa
英文名：vandetanib
适应症：
针对不能切除的晚期或转移性甲状腺髓样癌
作用机制：
口服的小分子多靶点酪酸激酶抑制剂(TKI),可同时作用于肿瘤细胞EGFR、VEGFR和RET酪氨酸激酶,还可选择性的抑制其他的酪氨酸激酶,以及丝氨酸/苏氨酸激酶,多靶点联合阻断信号传导,因此是一种多通道肿瘤信号传导抑制剂。
规格：
白色薄膜包衣片:25mg,50mg,100mg,200mg,300mg
用法用量：
单药用量为300mg/d,与化疗联合用量为100mg/d,口服每天1次,直至疾病进展。
不良反应：
最常见的毒副作用是腹泻、皮疹、恶心、高血压、厌食无症状的QT间期延长和蛋白尿。
制造商：
阿斯利康制药
类药物：
激酶抑制剂。
活性成分（S）：
凡德他尼100毫克*30片一盒，300毫克*30片一瓶，制表符。
指示（S）：
不能手术切除的局部晚期或转移性疾病患者的症状或甲状腺髓样癌。
药理学：
凡德他尼抑制酪氨酸激酶的活动，包括那些与表皮生长因子受体，血管内皮细胞生长因子受体和酪氨酸蛋白激酶6相关。它已被证明能够抑​​制内皮细胞迁移，增殖，存活，并在体外血管生成，抑制酪氨酸激酶磷酸化。凡德他尼降低肿瘤细胞诱导的血管生成，肿瘤血管通透性，并抑制在体内的肿瘤生长和转移的小鼠模型。
临床试验：
一个双盲对照研究，涉及331例不能手术切除的局部晚期或甲状腺髓样癌进行了评估凡德他尼与安慰剂无进展生存的改善。还审议了总生存率和整体客观反应率。一个显着改善，到凡德他尼的患者的无进展生存证明。的无进展生存期的主要分析时间，15％的患者已经死亡，并在两个治疗组之间的总生存期没有显着差异。整体客观反应率是44％者给予凡德他尼相比，安慰剂组为1％;所有的客观回应部分反应。
法律分类：
接收
成人：
请勿挤压选项卡。为口头或NGT组管理的非碳酸水可分散2盎司的标签，避免接触皮肤，粘膜的分散。 300毫克，每日一次。肾功能损害（肌酐清除率<50mL/min）：最初为200mg，每日一次。如果发生严重的毒性或QTc间期延长（见文献）减少剂量。不要错过的剂量范围内采取的下一个剂量的12小时。
儿童：
不推荐。
禁忌（S）：
先天性长QT综合征。
警告/注意事项：
低钙血症，低钾血症，低镁血症，QTcF的时间间隔> 450msec，尖端扭转型，缓慢性心律失常的历史，无偿心脏衰竭，近期咯血：不推荐。室性心律失常。近期心肌梗死。监视器电解质（尤其是钾离子，钙+，镁+），促甲状腺激素，和心电图QT间期延长在基线，2-4周和8-12周开始，然后每隔3个月后，和剂量减少或剂量中断后2周;减少如需要剂量。开始前纠正电解质紊乱。维护血清K +至少4mEq/mL。肝功能不全（Child - Pugh分级B或C）：不推荐。暂停治疗和后续如果发生呼吸困难，咳嗽，发烧，QTcF> 500毫秒，或后部白质脑病症状（RPLS）。避免阳光，紫外线光。老人。 （Cat.D）（可能对胎儿造成伤害，使用4个月期间和停药后的适当，有效的避孕）怀孕，哺乳期的母亲：不建议。
450msec，尖端扭转型，缓慢性心律失常的历史，无偿心脏衰竭，近期咯血：不推荐。室性心律失常。近期心肌梗死。监视器电解质（尤其是钾离子，钙+，镁+），促甲状腺激素，和心电图QT间期延长在基线，2-4周和8-12周开始，然后每隔3个月后，和剂量减少或剂量中断后2周;减少如需要剂量。开始前纠正电解质紊乱。维护血清K +至少4mEq/mL。肝功能不全（Child - Pugh分级B或C）：不推荐。暂停治疗和后续如果发生呼吸困难，咳嗽，发烧，QTcF> 500毫秒，或后部白质脑病症状（RPLS）。避免阳光，紫外线光。老人。 （Cat.D）（可能对胎儿造成伤害，使用4个月期间和停药后的适当，有效的避孕）怀孕，哺乳期的母亲：不建议。
500毫秒，或后部白质脑病症状（RPLS）。避免阳光，紫外线光。老人。 （Cat.D）（可能对胎儿造成伤害，使用4个月期间和停药后的适当，有效的避孕）怀孕，哺乳期的母亲：不建议。
相互作用（S）：
避免强CYP3A4诱导剂（如卡马西平，地塞米松，苯妥英，苯巴比妥，利福平，利福布丁，利福喷丁，圣约翰的草）。避免使用其他药物，可以延长QT间隔（例如，胺碘酮，丙吡胺，普鲁卡因胺，索他洛尔，多非利特，氯喹，克拉霉素，多拉司琼，格拉司琼，氟哌啶醇，匹莫齐特，美沙酮，莫西沙星）。
不良反应（S）：
（如果严重的中止）腹泻，皮疹，痤疮，恶心，高血压，头痛，乏力，食欲减退，腹痛，钙或葡萄糖下降，增加了ALT，QT间期延长，尖端扭转型，突然死亡，严重的皮肤反应（例如，史蒂文斯约翰逊综合征停止，如果发生），间质性肺疾病，缺血性脑血管事件，出血，心力衰竭，甲状腺功能减退，高血压危象，RPLS。
注：
如何提供：
标签30
最后更新：
2011年8月3日 

Generic Name and Formulations:
Vandetanib 100mg, 300mg, tabs.

Company:
AstraZeneca Pharmaceuticals

Indications for CAPRELSA:
Symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.

Adult Dose for CAPRELSA:
Do not crush tabs. May disperse tabs in 2oz noncarbonated water for oral or NGT administration; avoid contact of dispersion with skin, mucous membranes. 300mg once daily. Renal impairment (CrCl<50mL/min): initially 200mg once daily. Reduce dose if severe toxicity or QTc interval prolongation occurs (see literature). Do not take a missed dose within 12 hours of the next dose.

Children's Dose for CAPRELSA:
Not recommended.

Pharmacological Class:
Kinase inhibitor.

Contraindications:
Congenital long QT syndrome.

Warnings/Precautions:
Hypocalcemia, hypokalemia, hypomagnesemia, QTcF interval >450msec, history of torsades de pointes, bradyarrhythmias, uncompensated heart failure, recent hemoptysis: not recommended. Ventricular arrhythmias. Recent MI. Monitor electrolytes (esp. K+, Ca++, Mg++), TSH, and ECG for QT prolongation at baseline, 2–4 weeks and 8–12 weeks after starting, then every 3 months, and after dose reductions or dose interruptions >2 weeks; reduce dose as needed. Correct electrolyte disturbances before starting. Maintain serum K+ at least 4mEq/mL. Hepatic impairment (Child-Pugh B or C): not recommended. Suspend therapy and follow-up if dyspnea, cough, fever, QTcF>500msec, or posterior leukoencephalopathy symptoms (RPLS) occur. Avoid sun, UV light. Elderly. Pregnancy (Cat. D) (may cause fetal harm; use appropriate effective contraception during and for 4 months after stopping therapy), nursing mothers: not recommended.

Interactions:
Avoid strong CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenytoin, phenobarbital, rifampin, rifabutin, rifapentine, St. John's Wort). Avoid other drugs that can prolong QT interval (eg, amiodarone, disopyramide, procainamide, sotalol, dofetilide, chloroquine, clarithromycin, dolasetron, granisetron, haloperidol, pimozide, methadone, moxifloxacin).

Adverse Reactions:
Diarrhea (suspend if severe), rash, acne, nausea, hypertension, headache, fatigue, decreased appetite, abdominal pain, decreased calcium or glucose, increased ALT; QT prolongation, torsades de pointes, sudden death, severe skin reactions (eg, Stevens-Johnson syndrome; discontinue if occurs), interstitial lung disease, ischemic cerebrovascular events, hemorrhage, heart failure, hypothyroidism, hypertensive crisis, RPLS.

Note:
Prescribers and pharmacies must enroll in the Caprelsa REMS program by calling (800) 236-9933 or visit www.caprelsarems.com.

How Supplied:
Tabs—30
Indication

CAPRELSA is a kinase inhibitor indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.
Use of CAPRELSA in patients with indolent, asymptomatic or slowly progressing disease should be carefully considered because of the treatment related risks of CAPRELSA.
Important Safety Information, including boxed WARNING WARNING: QT PROLONGATION, TORSADES DE POINTES, AND SUDDEN DEATH
•CAPRELSA can prolong the QT interval. Torsades de pointes and sudden death have been reported in patients receiving CAPRELSA.
•CAPRELSA should not be used in patients with hypocalcemia, hypokalemia, hypomagnesemia, or long QT syndrome. Hypocalcemia, hypokalemia and/or hypomagnesemia must be corrected prior to CAPRELSA administration and should be periodically monitored.
•Drugs known to prolong the QT interval should be avoided. If a drug known to prolong the QT interval must be administered, more frequent ECG monitoring is recommended.
•Given the half-life of 19 days, ECGs should be obtained to monitor the QT at baseline, at 2-4 weeks and 8-12 weeks after starting treatment with CAPRELSA and every 3 months thereafter. Following any dose reduction for QT prolongation, or any dose interruptions greater than 2 weeks, QT assessment should be conducted as described above.
•Because of the 19-day half-life, adverse reactions including a prolonged QT interval may not resolve quickly. Monitor appropriately.
•Only prescribers and pharmacies certified with the restricted distribution program are able to prescribe and dispense CAPRELSA.
•Do not use CAPRELSA in patients with congenital long QT syndrome.
•Because of the risk of QT prolongation, ECGs and levels of serum potassium, calcium, magnesium, and TSH should be monitored at baseline, at 2-4 weeks and 8-12 weeks after starting treatment with CAPRELSA, and every 3 months thereafter and following dose adjustments.
•Severe skin reactions (including Stevens-Johnson syndrome), some leading to death, have been reported and may prompt permanent discontinuation of CAPRELSA.
•Interstitial lung disease (ILD) has been observed with CAPRELSA and deaths have been reported. Interrupt CAPRELSA treatment and investigate unexplained dyspnea, cough, and fever.
•Ischemic cerebrovascular events, serious hemorrhagic events, and heart failure have been observed with CAPRELSA and some cases have been fatal.
•Diarrhea has been observed with CAPRELSA. Serum electrolytes and ECGs should be carefully monitored in cases of diarrhea because of the risk of QT prolongation with CAPRELSA. If severe diarrhea develops, CAPRELSA treatment should be stopped until diarrhea improves.
•Hypothyroidism, hypertension, and reversible posterior leukoencephalopathy syndrome (RPLS) have been observed with CAPRELSA.
•The concomitant use of known strong CYP3A4 inducers may reduce drug levels of CAPRELSA and should be avoided. The administration of CAPRELSA with antiarrhythmic drugs and other drugs that may prolong the QT interval should be avoided.
•CAPRELSA exposure is increased in patients with impaired renal function. The starting dose of CAPRELSA should be reduced to 200 mg in patients with moderate to severe renal impairment and the QT interval should be monitored closely.
•CAPRELSA is not recommended for patients with moderate and severe hepatic impairment, since safety and efficacy have not been established.
•CAPRELSA can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid pregnancy while receiving CAPRELSA and for at least 4 months following treatment.
•The most common adverse drug reactions (>20%) seen with CAPRELSA are diarrhea (57%), rash (53%), acne (35%), nausea (33%), hypertension (33%), headache (26%), fatigue (24%), decreased appetite (21%), and abdominal pain (21%). The most common laboratory abnormalities (>20%) were decreased calcium (57%), increased ALT (51%), and decreased glucose (24%).
•CAPRELSA REMS Program: Because of the risks of QT prolongation, Torsades de pointes and sudden death, CAPRELSA is available only through the CAPRELSA REMS Program. Only prescribers and pharmacies certified with the restricted distribution program are able to prescribe and dispense CAPRELSA. To learn about the specific REMS requirements and to enroll in the CAPRELSA REMS Program call 1-800-236-9933 or visit www.caprelsarems.com.